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1. Recommendations for standardized human pedigree nomenclature

Author: Human Genome Center, University of Michigan, Ann Arbor, Michigan, Center for Perinatal Studies, Swedish Medical Center, Seattle, Washington, Genetics Services Section, Department of Health, Seattle, Washington, Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington; Medical Genetics, RG-25, University of Washington Medical Center, 98195, Seattle, Washington, Division of Human Genetics, University of California at Irvine, Orange, California, Obstetrics and Gynecology, University of Washington Medical Center, Seattle, Washington, Medical Genetics, RG-25, University of Washington Medical Center, 98195, Seattle, Washington, Division of Genetics, University of South Carolina School of Medicine, Columbia, South Carolina, Ann Arbor, Steinhaus, Kathryn A., O'Sullivan, Corrine K., Hamanishi, Jan, Vincent, Victoria, Markel, Dorene S., Lochner-Doyle, Debra, Bennett, Robin L., Uhrich, Stefanie B., Resta, Robert G., Human Genome Center, University of Michigan, Ann Arbor, Michigan, Center for Perinatal Studies, Swedish Medical Center, Seattle, Washington, Genetics Services Section, Department of Health, Seattle, Washington, Division of Medical Genetics, University of Washington Medical Center, Seattle, Washington; Medical Genetics, RG-25, University of Washington Medical Center, 98195, Seattle, Washington, Division of Human Genetics, University of California at Irvine, Orange, California, Obstetrics and Gynecology, University of Washington Medical Center, Seattle, Washington, Medical Genetics, RG-25, University of Washington Medical Center, 98195, Seattle, Washington, Division of Genetics, University of South Carolina School of Medicine, Columbia, South Carolina, Ann Arbor, Steinhaus, Kathryn A., O'Sullivan, Corrine K., Hamanishi, Jan, Vincent, Victoria, Markel, Dorene S., Lochner-Doyle, Debra, Bennett, Robin L., Uhrich, Stefanie B., and Resta, Robert G.
Abstract: The construction of an accurate family pedigree is a fundamental component of a clinical genetic evaluation and of human genetic research. Previous surveys of genetic counselors and human genetic publications have demonstrated significant inconsistencies in the usage of common pedigree symbols representing situations such as pregnancy, termination of pregnancy, miscarriage, and adoption, as well as less common scenarios such as pregnancies conceived through assisted reproductive technologies. The Pedigree Standardization Task Force (PSTF) was organized through the Professional Issues Committee of the National Society of Genetic Counselors, to establish recommendations for universal standards in human pedigree nomenclature. Nomenclature was chosen based on current usage, consistency among symbols, computer compatibility, and the adaptability of symbols to reflect the rapid technical advances in human genetics. Preliminary recommendations were presented for review at three national meetings of human genetic professionals and sent to>100 human genetic professionals for review. On the basis of this review process, the recommendations of the PSTF for standardized human pedigree nomenclature are presented here. By incorporating these recommendations into medical genetics professional training programs, board examinations, genetic publications, and pedigree software, the adoption of uniform pedigree nomenclature can begin. Usage of standardized pedigree nomenclature will reduce the chances for incorrect interpretation of patient and family medical and genetic information. It may also improve the quality of patient care provided by genetic professionals and facilitate communication between researchers involved with genetic family studies.
Published: 2006

2. The 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis: Phase 2 methodological report

Author: University of Michigan, Ann Arbor, Boston University School of Medicine, Boston, Massachusetts, Medical University of Vienna, Vienna, Austria ; Dr. Aletaha has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, UCB, Schering-Plough, Wyeth, and Roche (less than $10,000 each)., Arthritis Research UK, Chesterfield, UK, Ministry of Health, Auckland, New Zealand ; Dr. Naden has received consulting fees from the American College of Rheumatology in regard to the methodology of developing weighted scoring systems (more than $10,000)., University of Pittsburgh, Pittsburgh, Pennsylvania, Johns Hopkins University, Baltimore, Maryland ; Dr. Bingham has received consulting fees, speaking fees, and/or honoraria from UCB, Roche, Genentech, Celgene, and Merck Serono (less than $10,000 each); he has received research and/or educational grant support from Bristol-Myers Squibb, Genentech, UCB, Centocor, Abbott, and Amgen., California Pacific Medical Center and University of California, San Francisco ; Dr. Birnbaum has received consulting fees, speaking fees, and/or honoraria from Amgen, Pfizer, Centocor, Abbott, and UCB (less than $10,000 each)., Charit?? Hospital???University Medicine Berlin, Free University and Humboldt University, Berlin, Germany ; Dr. Burmester has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Pfizer, UCB, and Roche (less than $10,000 each)., Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada ; Dr. Bykerk has received consulting fees, speaking fees, and/or honoraria from Amgen, Wyeth, Abbott, Schering-Plough, Roche, Bristol-Myers Squibb, and UCB (less than $10,000 each); her spouse is employed by Genzyme and owns stock in the company., National Jewish Medical and Research Center, Denver, Colorado ; Dr. Cohen has received consulting fees, speaking fees, and/or honoraria from UCB, Genentech, Bristol-Myers Squibb, and Human Genome Sciences (less than $10,000 each)., Lapeyronie Hospital and Montpellier I University, Montpellier, France ; Dr. Combe has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Pfizer, Roche, Schering-Plough, and Merck, Sharpe, and Dohme (less than $10,000 each)., Brigham and Women's Hospital and Harvard University, Boston, Massachusetts, Cochin Hospital, Assistance Publique H??pitaux de Paris, and Paris-Descartes University, Paris, France, University of Leeds and NIHR Leeds Biomedical Research Unit, Leeds, UK ; Dr. Emery has received consulting fees, speaking fees, and/or honoraria from Pfizer, Abbott, Centocor, UCB, Roche, Bristol-Myers Squibb, and Merck, Sharpe, and Dohme (less than $10,000 each)., School of Medicine, Catholic University of the Sacred Heart, Rome, Italy ; Dr. Ferraccioli holds a patent for T cell receptor clonotype analysis (PCT/IB 2008/053152 NP)., Erasmus Medical Center and University of Rotterdam, Rotterdam, The Netherlands, University of Colorado School of Medicine, Denver, Leiden University Medical Center, Leiden, The Netherlands ; Dr. Huizinga has received consulting fees, speaking fees, and/or honoraria from Schering-Plough, Bristol-Myers Squibb, UCB, Biotest AG, Wyeth/Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, and Axis-Shield (less than $10,000 each)., University of California, San Diego ; Dr. Kavanaugh has conducted clinical research for Amgen, Abbott, Bristol-Myers Squibb, UCB, Roche, Centocor, Genentech, and Sanofi-Aventis., UMassMemorial Medical Center and University of Massachusetts Medical School, Worcester ; Dr. Kay has received consulting fees from Array BioPharma, Bristol-Myers Squibb, Celgene, Centocor, Genentech, Roche, UCB, and Sanofi-Aventis (less than $10,000 each)., David Geffen School of Medicine at University of California, Los Angeles ; Dr. Khanna has received consulting fees, speaking fees, and/or honoraria from UCB and Abbott (less than $10,000 each)., Diakonhjemmet Hospital, Oslo, Norway, Swedish Medical Center and University of Washington, Seattle ; Dr. Mease has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor, Roche, Genentech, UCB, Pfizer, Novartis, and Eli Lilly (less than $10,000 each)., McGill University Health Centre and McGill University, Montreal, Quebec, Canada ; Dr. M??nard has received unrestricted educational and research grants as well as consulting and speaking fees from Abbott, Amgen, Inova, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth (less than $10,000 each) and investigator-initiated research grants from Bristol-Myers Squibb, EuroImmun AG, and Roche (more than $10,000 each); he owns stock or stock options in Merck; and he has a license agreement with EuroImmun AG for an anti-Sa enzyme-linked immunosorbent assay., University of Pittsburgh, Pittsburgh, Pennsylvania ; Dr. Moreland has received consulting fees, speaking fees, and/or honoraria from Biogen Idec, Centocor, Pfizer, Takeda, KaloBios, ChemoCentryx, UCB, Genentech, Incyte, and Eli Lilly (less than $10,000 each)., University of North Carolina, Chapel Hill, New York University Hospital for Joint Diseases, New York, New York ; Dr. Pincus has received consulting fees, speaking fees, and/or honoraria from Amgen, Abbott, Bristol-Myers Squibb, Centocor, UCB, Wyeth, and Genentech (less than $10,000 each) and investigator-initiated research grants from Amgen, Bristol-Myers Squibb, UCB, and Centocor., Seattle Children's Hospital, Seattle, Washington, Medical University of Vienna, Vienna, Austria, Institute of Rheumatology, Warsaw, Poland ; Dr. Stanislawska-Biernat has received speaking fees from Abbott and Pfizer (less than $10,000 each)., University of Manchester, Manchester, UK, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands, UMassMemorial Medical Center and University of Massachusetts Medical School, Worcester, Institute of Rheumatology, Prague, Czech Republic ; Dr. Vencovsk?? has received speaking fees from Pfizer, UCB, Abbott, Roche, and Merck, Sharpe, and Dohme (less than $10,000 each)., National Data Bank for Rheumatic Diseases and University of Kansas, Wichita, Women's College Hospital and University of Toronto, Toronto, Ontario, Canada ; Department of Medicine, Women's College Hospital, 76 Grenville Street, 8th Floor, Room 815, Toronto, Ontario M5S 1B2, Canada, Neogi, Tuhina, Aletaha, Daniel, Silman, Alan J., Naden, Raymond L., Felson, David T., Aggarwal, Rohit, Bingham, Clifton O., Birnbaum, Neal S., Burmester, Gerd R., Bykerk, Vivian P., Cohen, Marc D., Combe, Bernard, Costenbader, Karen H., Dougados, Maxime, Emery, Paul, Ferraccioli, Gianfranco, Hazes, Johanna M. W., Hobbs, Kathryn, Huizinga, Tom W. J., Kavanaugh, Arthur, Kay, Jonathan, Khanna, Dinesh, Kvien, Tore K., Laing, Timothy, Liao, Katherine, Mease, Philip, M??nard, Henri A., Moreland, Larry W., Nair, Raj, Pincus, Theodore, Ringold, Sarah, Smolen, Josef S., Stanislawska-Biernat, Ewa, Symmons, Deborah, Tak, Paul P., Upchurch, Katherine S., Vencovsk??, Jir??, Wolfe, Frederick, Hawker, Gillian, University of Michigan, Ann Arbor, Boston University School of Medicine, Boston, Massachusetts, Medical University of Vienna, Vienna, Austria ; Dr. Aletaha has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, UCB, Schering-Plough, Wyeth, and Roche (less than $10,000 each)., Arthritis Research UK, Chesterfield, UK, Ministry of Health, Auckland, New Zealand ; Dr. Naden has received consulting fees from the American College of Rheumatology in regard to the methodology of developing weighted scoring systems (more than $10,000)., University of Pittsburgh, Pittsburgh, Pennsylvania, Johns Hopkins University, Baltimore, Maryland ; Dr. Bingham has received consulting fees, speaking fees, and/or honoraria from UCB, Roche, Genentech, Celgene, and Merck Serono (less than $10,000 each); he has received research and/or educational grant support from Bristol-Myers Squibb, Genentech, UCB, Centocor, Abbott, and Amgen., California Pacific Medical Center and University of California, San Francisco ; Dr. Birnbaum has received consulting fees, speaking fees, and/or honoraria from Amgen, Pfizer, Centocor, Abbott, and UCB (less than $10,000 each)., Charit?? Hospital???University Medicine Berlin, Free University and Humboldt University, Berlin, Germany ; Dr. Burmester has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Pfizer, UCB, and Roche (less than $10,000 each)., Mount Sinai Hospital and University of Toronto, Toronto, Ontario, Canada ; Dr. Bykerk has received consulting fees, speaking fees, and/or honoraria from Amgen, Wyeth, Abbott, Schering-Plough, Roche, Bristol-Myers Squibb, and UCB (less than $10,000 each); her spouse is employed by Genzyme and owns stock in the company., National Jewish Medical and Research Center, Denver, Colorado ; Dr. Cohen has received consulting fees, speaking fees, and/or honoraria from UCB, Genentech, Bristol-Myers Squibb, and Human Genome Sciences (less than $10,000 each)., Lapeyronie Hospital and Montpellier I University, Montpellier, France ; Dr. Combe has received consulting fees, speaking fees, and/or honoraria from Abbott, Bristol-Myers Squibb, Pfizer, Roche, Schering-Plough, and Merck, Sharpe, and Dohme (less than $10,000 each)., Brigham and Women's Hospital and Harvard University, Boston, Massachusetts, Cochin Hospital, Assistance Publique H??pitaux de Paris, and Paris-Descartes University, Paris, France, University of Leeds and NIHR Leeds Biomedical Research Unit, Leeds, UK ; Dr. Emery has received consulting fees, speaking fees, and/or honoraria from Pfizer, Abbott, Centocor, UCB, Roche, Bristol-Myers Squibb, and Merck, Sharpe, and Dohme (less than $10,000 each)., School of Medicine, Catholic University of the Sacred Heart, Rome, Italy ; Dr. Ferraccioli holds a patent for T cell receptor clonotype analysis (PCT/IB 2008/053152 NP)., Erasmus Medical Center and University of Rotterdam, Rotterdam, The Netherlands, University of Colorado School of Medicine, Denver, Leiden University Medical Center, Leiden, The Netherlands ; Dr. Huizinga has received consulting fees, speaking fees, and/or honoraria from Schering-Plough, Bristol-Myers Squibb, UCB, Biotest AG, Wyeth/Pfizer, Novartis, Roche, Sanofi-Aventis, Abbott, and Axis-Shield (less than $10,000 each)., University of California, San Diego ; Dr. Kavanaugh has conducted clinical research for Amgen, Abbott, Bristol-Myers Squibb, UCB, Roche, Centocor, Genentech, and Sanofi-Aventis., UMassMemorial Medical Center and University of Massachusetts Medical School, Worcester ; Dr. Kay has received consulting fees from Array BioPharma, Bristol-Myers Squibb, Celgene, Centocor, Genentech, Roche, UCB, and Sanofi-Aventis (less than $10,000 each)., David Geffen School of Medicine at University of California, Los Angeles ; Dr. Khanna has received consulting fees, speaking fees, and/or honoraria from UCB and Abbott (less than $10,000 each)., Diakonhjemmet Hospital, Oslo, Norway, Swedish Medical Center and University of Washington, Seattle ; Dr. Mease has received consulting fees, speaking fees, and/or honoraria from Abbott, Amgen, Biogen Idec, Bristol-Myers Squibb, Centocor, Roche, Genentech, UCB, Pfizer, Novartis, and Eli Lilly (less than $10,000 each)., McGill University Health Centre and McGill University, Montreal, Quebec, Canada ; Dr. M??nard has received unrestricted educational and research grants as well as consulting and speaking fees from Abbott, Amgen, Inova, Merck, Pfizer, Roche, Schering-Plough, UCB, and Wyeth (less than $10,000 each) and investigator-initiated research grants from Bristol-Myers Squibb, EuroImmun AG, and Roche (more than $10,000 each); he owns stock or stock options in Merck; and he has a license agreement with EuroImmun AG for an anti-Sa enzyme-linked immunosorbent assay., University of Pittsburgh, Pittsburgh, Pennsylvania ; Dr. Moreland has received consulting fees, speaking fees, and/or honoraria from Biogen Idec, Centocor, Pfizer, Takeda, KaloBios, ChemoCentryx, UCB, Genentech, Incyte, and Eli Lilly (less than $10,000 each)., University of North Carolina, Chapel Hill, New York University Hospital for Joint Diseases, New York, New York ; Dr. Pincus has received consulting fees, speaking fees, and/or honoraria from Amgen, Abbott, Bristol-Myers Squibb, Centocor, UCB, Wyeth, and Genentech (less than $10,000 each) and investigator-initiated research grants from Amgen, Bristol-Myers Squibb, UCB, and Centocor., Seattle Children's Hospital, Seattle, Washington, Medical University of Vienna, Vienna, Austria, Institute of Rheumatology, Warsaw, Poland ; Dr. Stanislawska-Biernat has received speaking fees from Abbott and Pfizer (less than $10,000 each)., University of Manchester, Manchester, UK, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands, UMassMemorial Medical Center and University of Massachusetts Medical School, Worcester, Institute of Rheumatology, Prague, Czech Republic ; Dr. Vencovsk?? has received speaking fees from Pfizer, UCB, Abbott, Roche, and Merck, Sharpe, and Dohme (less than $10,000 each)., National Data Bank for Rheumatic Diseases and University of Kansas, Wichita, Women's College Hospital and University of Toronto, Toronto, Ontario, Canada ; Department of Medicine, Women's College Hospital, 76 Grenville Street, 8th Floor, Room 815, Toronto, Ontario M5S 1B2, Canada, Neogi, Tuhina, Aletaha, Daniel, Silman, Alan J., Naden, Raymond L., Felson, David T., Aggarwal, Rohit, Bingham, Clifton O., Birnbaum, Neal S., Burmester, Gerd R., Bykerk, Vivian P., Cohen, Marc D., Combe, Bernard, Costenbader, Karen H., Dougados, Maxime, Emery, Paul, Ferraccioli, Gianfranco, Hazes, Johanna M. W., Hobbs, Kathryn, Huizinga, Tom W. J., Kavanaugh, Arthur, Kay, Jonathan, Khanna, Dinesh, Kvien, Tore K., Laing, Timothy, Liao, Katherine, Mease, Philip, M??nard, Henri A., Moreland, Larry W., Nair, Raj, Pincus, Theodore, Ringold, Sarah, Smolen, Josef S., Stanislawska-Biernat, Ewa, Symmons, Deborah, Tak, Paul P., Upchurch, Katherine S., Vencovsk??, Jir??, Wolfe, Frederick, and Hawker, Gillian
Abstract: Objective The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set. Methods Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of ???developing RA,??? complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis. Results The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach. Conclusion The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.
Published: 2010

3. Effect of bimekizumab on symptoms and impact of disease in patients with psoriatic arthritis over 3 years: results from BE ACTIVE

Author: Philip J Mease, Akihiko Asahina, Dafna D Gladman, Yoshiya Tanaka, William Tillett, Barbara Ink, Deepak Assudani, Christine de la Loge, Jason Coarse, Jason Eells, Laure Gossec, University of Washington [Seattle], Swedish Medical Center [Seattle, WA, USA], The Jikei University School of Medicine, University of Toronto, University of Occupational and Environmental Health [Kitakyushu] (UEOH), University of Bath [Bath], UCB Pharma [Slough], UCB Pharma [Brussels], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and HAL-SU, Gestionnaire
Subjects: [SDV] Life Sciences [q-bio], physical function, Rheumatology, Psoriatic arthritis, [SDV]Life Sciences [q-bio], fatigue, pain, Pharmacology (medical), bimekizumab, patient-reported outcome measures
Abstract: Objectives Evaluate effects of long-term bimekizumab treatment on patient-reported outcome (PRO) measures, symptoms and the impact of PsA on patients. Methods Patients with active PsA were enrolled into BE ACTIVE, a 48-week randomised controlled trial (NCT02969525). After Week 48, patients could enter a 104-week open-label extension (NCT03347110), receiving bimekizumab 160 mg every four weeks. PRO measures assessed included arthritis pain visual analogue scale (VAS), PsA Impact of Disease (PsAID)-9, 36-Item Short Form Survey (SF-36) and HAQ-Disability Index (HAQ-DI). Results were analysed as mean (S.E.M.) changes from baseline (CfB) from Week 0 to the end of the open-label extension (3 years) and as percentage of patients reaching patient-acceptable symptom state (PASS) for global impact (PsAID-9 total score ≤4) and normal function (HAQ-DI total score Results In 206 patients (mean age 49.3 years, 51.0% male), completion rate was high; 161 (78.2%) patients completed Week 152. Bimekizumab treatment was associated with long-term sustained improvements in pain [arthritis pain VAS CfB; Week 48: −29.9 (1.9); Week 152: −32.0 (1.9)] and fatigue [PsAID-9 fatigue CfB; −2.4 (0.2); −2.7 (0.2)]. High percentages of patients achieved acceptable symptom state (PsAID-9 PASS: 75.2%; 65.0%) and normalised function (HAQ-DI Conclusions Bimekizumab treatment was associated with long-term sustained improvements in pain and fatigue, reducing overall impact of PsA on patients. Physical function and quality of life improved up to 3 years. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02969525, NCT03347110.
Published: 2022
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4. Guselkumab demonstrated an independent treatment effect in reducing fatigue after adjustment for clinical response—results from two phase 3 clinical trials of 1120 patients with active psoriatic arthritis

Author: Xiwu Lin, Laure Gossec, Elizabeth C. Hsia, Arthur Kavanaugh, A. Kollmeier, Chenglong Han, B. Zhou, Atul Deodhar, Philip S. Helliwell, May Shawi, Chetan S Karyekar, Philip J. Mease, Proton Rahman, Memorial University of Newfoundland [St. John's], University of Washington [Seattle], Swedish Medical Center [Seattle, WA, USA], University of Leeds, Oregon Health and Science University [Portland] (OHSU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of California [San Diego] (UC San Diego), University of California, Janssen Research & Development, Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], HAL-SU, Gestionnaire, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of California (UC), and University of Pennsylvania-University of Pennsylvania
Subjects: medicine.medical_specialty, Biologic, Population, Diseases of the musculoskeletal system, Placebo, Antibodies, Monoclonal, Humanized, Severity of Illness Index, Interleukin-23, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Double-Blind Method, Internal medicine, Medicine, Humans, 030212 general & internal medicine, Dosing, education, Fatigue, Patient-reported outcome, 030203 arthritis & rheumatology, education.field_of_study, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, business.industry, Arthritis, Psoriatic, Repeated measures design, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, 3. Good health, Clinical trial, Guselkumab, Treatment Outcome, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, RC925-935, Antirheumatic Agents, p19 subunit, Mediation analysis, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, Research Article
Abstract: BackgroundThe interleukin-23p19-subunit inhibitor guselkumab effectively treats signs and symptoms of psoriatic arthritis (PsA). We evaluated the effect of guselkumab on fatigue.MethodsAcross two phase 3 trials of guselkumab (DISCOVER-1, DISCOVER-2), patients with active PsA despite standard therapy were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W,N= 373); guselkumab 100 mg at week 0, week 4, and then Q8W (N= 375); or placebo (N= 372) through week 24, after which patients in the placebo group crossed over to guselkumab Q4W. Fatigue was measured as a secondary endpoint using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue instrument (range 0–52, higher scores indicate less fatigue). Least-squares mean changes in FACIT-Fatigue scores were compared between treatments using a mixed-effect model for repeated measures. Mediation analysis was used to adjust for indirect effects on fatigue deriving from improvement in other outcomes, including ≥20% improvement in American College of Rheumatology criteria (ACR20; prespecified), minimal disease activity (MDA; post hoc), or C-reactive protein (CRP; post hoc).ResultsBaseline mean (SD) FACIT-Fatigue scores in DISCOVER-1 (N= 381) and DISCOVER-2 (N= 739), ranging from 29.1 (9.5) to 31.4 (10.1), indicated substantial levels of fatigue relative to the United States general population (43.6 [9.4]). Across studies, mean improvements, and proportions of patients with ≥4-point improvements, in FACIT-Fatigue scores at week 24 with guselkumab Q4W and Q8W (5.6–7.6 and 54–63%, respectively) were larger vs placebo (2.2–3.6 and 35–46%). Improvement in FACIT-Fatigue scores with guselkumab was sustained from week 24 to week 52, with moderate-to-large effect sizes (Cohen’sd= 0.52–0.81 at week 24; 0.66–0.91 at week 52). Mediation analyses demonstrated that substantial proportions of the effects of guselkumab vs placebo on fatigue were direct effect, after adjusting for achievement of ACR20 (Q4W 69–70%, Q8W 12–36% direct effect) or MDA (72–92% across dosing regimens) response or for change in serum CRP concentrations (82–88% across dosing regimens).ConclusionsIn patients with active PsA, guselkumab 100 mg Q4W or Q8W led to clinically meaningful and sustained improvements in fatigue through 1 year. A substantial portion of the improvement in FACIT-Fatigue scores induced by guselkumab was independent of effects on the achievement of other select outcomes.Trial registrationName of the registry: ClinicalTrials.govTrial registrations: DISCOVER-1, NCT03162796; DISCOVER-2, NCT03158285Date of registration: DISCOVER-1, May 22, 2017; DISCOVER-2, May 18, 2017URLs of the trial registry record:DISCOVER-1,https://clinicaltrials.gov/ct2/show/NCT03162796?term=NCT03162796&draw=1&rank=1DISCOVER-2,https://clinicaltrials.gov/ct2/show/NCT03158285?term=NCT03158285&draw=2&rank=1
Published: 2021
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5. Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic

Author: Ajit S. Puri, Allan Taylor, Huynh Le Vu, Tatemi Todaka, Teddy Y. Wu, Octavio M. Pontes-Neto, Eytan Raz, Pedro Lylyk, Jasmine Johann, Roberta Novakovic, Hormuzdiyar H. Dasenbrock, Francisco Mont’Alverne, Nobuyuki Sakai, Melanie Walker, Hugh Stephen Winters, Ossama Mansour, Yohei Takenobu, Gregory Walker, Miki Fujimura, Saif Bushnaq, Odysseas Kargiotis, Nabeel Herial, Markus A Möhlenbruch, Malveeka Sharma, Hiroshi Tokimura, Maxim Mokin, Jean Raymond, Michael D. Hill, Amal Abou-Hamden, Leonardo Renieri, Serdar Geyik, Yuri Sugiura, Luisa Fonseca, Roberto Crosa, Fabricio O Lima, Ameer E Hassan, Viet Quy Nguyen, Jane G. Morris, Steven W. Hetts, Jawad F. Kirmani, Matthew S. Tenser, Muhammad M. Qureshi, Gianmarco Bernava, Mahmoud H Mohammaden, Verónica V. Olavarría, Jun Deguchi, André Beer-Furlan, Steve M. Cordina, Hiroshi Yamagami, Mohamad Abdalkader, Toshiyuki Fujinaka, Clifford J. Eskey, Rotem Sivan-Hoffmann, Hao Zhang, Anirudh Kulkarni, Brendan Steinfort, Özlem Aykaç, Barbara Voetsch, Alex Brehm, Italo Linfante, Wenguo Huang, Omer Eker, M. Luis Silva, Pascal Jabbour, Lissa Peeling, Mollie McDermott, Pascale Lavoie, Kazutaka Sonoda, Thomas Devlin, Alicia C. Castonguay, Jin Soo Lee, Diogo C Haussen, Dileep R. Yavagal, Thanh N. Nguyen, Umair Rashid, Vasu Saini, Raghid Kikano, Hiroyuki Hashimoto, Masaaki Uno, Saima Ahmad, Artem Kaliaev, Eiji Hagashi, Ajay K. Wakhloo, Romain Bourcier, Ryoo Yamamoto, Jesse M. Thon, Georgios Tsivgoulis, Dorothea Altschul, Achmad Fidaus Sani, Satoshi Yamada, Varsha Singh, David S Liebeskind, Tatsuo Amano, Anchalee Churojana, Juan F. Arenillas, Junichi Iida, Charles C. Matouk, Nobuyuki Ohara, Osama O. Zaidat, Mario Martínez-Galdámez, Chandril Chugh, Don Frei, Vanessa Chalumeau, Brijesh P Mehta, Marios Psychogios, Anna Luisa Kühn, Leticia C Rebello, Xianjin Shang, Hosam Al-Jehani, Hiroki Fukuda, Hong Gee Roh, Gisele Sampaio Silva, Rakesh Khatri, Kenichi Todo, Amal Al Hashmi, Alex Bou Chebl, Sunil A Sheth, Zhongming Qiu, Oriana Cornett, Zhengzhou Yuan, Wazim Izzath, Hesham Masoud, Rodrigo Rivera, Michel Piotin, Vikram Huded, Mamoru Murakami, Mohamed Teleb, Viktor Szeder, Ruchir Shah, Dheeraj Gandhi, John Thornton, Michael Chen, Vitor Mendes Pereira, Nadia Hammami, Alice Ma, Anna M. Cervantes-Arslanian, James E. Siegler, Seby John, Carlos Ynigo Lopez, Mudassir Farooqui, David Ozretić, Takuya Kanamaru, Romain Guile, Daisuke Watanabe, Kosuke Miyake, Alejandro Rodriguez Vasquez, Patrick Nicholson, Yuki Yamamoto, William J. Mack, Naoto Kimura, Simon Mathew John, Robert Fahed, Yuji Matsumaru, David Y. Chung, Rishi Gupta, Ryuhei Kono, Michael Frankel, Victor S. Lopez Rivera, Johanna T. Fifi, Raul G Nogueira, Paolo Machi, Tudor G. Jovin, Jordi Blasco, Emma Griffin, Salvatore Mangiafico, Masafumi Morimoto, Jun Luo, Santiago Ortega-Gutierrez, Monika Killer-Oberpfalzer, Daniel Giansante Abud, Syed I. Hussain, Fawaz Al-Mufti, Yusuke Sugimura, Atilla Özcan Özdemir, Stephan A. Mayer, Sumeet Multani, Adel Alhazzani, Alhamza R Al-Bayati, Michael Kelly, Lee A Birnbaum, Shadi Yaghi, Jeyaraj D Pandian, Ji Man Hong, Junsuke Shimbo, Johnny Ho-Yin Wong, Elena A. Cora, Laura Mechtouff, Pedro S.C. Magalhães, Pablo M. Lavados, Yuichi Murayama, Dong Hun Shin, Simon Nagel, Ken Wong, Jose Antonio Fiorot, Jeremy Payne, Randall C. Edgell, Adrienne Weeks, CarMeN, laboratoire, Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Emory University School of Medicine, Emory University [Atlanta, GA], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), National Hospital Organization Osaka National Hospital [Japon] (NHO Osaka National Hospital), Alexandria University [Alexandrie], Boston Medical Center [Boston, MA, USA] (BMC), Xinqiao Hospital [Chongqing, China] (XH), University of Cape Town, La Sagrada Familia Clinic/Clínica La Sagrada Familia [Buenos Aires, Argentina] (LSFC), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Hospital General de Fortaleza [Fortaleza, Brazil] (HGF), Nottingham University Hospitals NHS Trust [UK], Kobe City Medical Center General Hospital [Kobe, Hyogo, Japan] (KCMCGH), Azienda Ospedaliero-Universitaria Careggi [Firenze, Toscana, Italy] (AOUC), University Hospital Centre Zagreb, Partenaires INRAE, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cleveland Clinic Abu Dhabi [Abou Dabi, Émirats arabes unis], Hôpital de Beaumont [Dublin, Ireland] (HB), Hospital-Estadual Central [Vitoria, Brazil] (HEC), Instituto de NeuroCirugía Asenjo, Institut national de neurologie Mongi-Ben Hamida [Tunis], Hue Central Hospital [Thua Thien Hue, Vietnam] (HCH), University of California [San Francisco] (UC San Francisco), University of California (UC), Centre hospitalier universitaire de Nantes (CHU Nantes), Washington University School of Medicine (WUSM), University of Washington [Seattle], Englewood Hospital and Medical Center [Englewood], Jefferson (Philadelphia University + Thomas Jefferson University), Westchester Medical Center [Valhalla, New York, USA] (WMC), Eskisehir Osmangazi University, University of Maryland School of Medicine, University of Maryland System, MAX Superspecialty Hospital [Saket, New Delhi, India] (MSH), Yale School of Medicine [New Haven, Connecticut] (YSM), Université Laval [Québec] (ULaval), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Rush University Medical Center [Chicago], Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Toronto, NH Mazumdar Shah Medical Center [Bangalore, India] (NHMSMC), IMS Tokyo-Katsushika General Hospital [Tokyo, Japan], Gachon University [Seongnam, Korea] (GU), Hospital Municipal Sao Jose [Joinville, Santa Catarina, Brazil] (HMSJ), Lau Medical Center [Beirut, Lebanon] (LMC), University of Iowa [Iowa City], Royal Adelaide Hospital [Adelaide Australia], Kyorin University [Tokyo, Japan], Yokohama Brain and Spine Center [Yokohama, Japan] (YBSC), Dalhousie University [Halifax], Rambam Health Care Campus [Haifa, Israel], Centro Endovascular Neurologico Medica Uruguaya [Montevideo, Uruguay] (CENMU), Heidelberg University Hospital [Heidelberg], Imam Abdulrahman bin Faisal University [Alkhobar, Saudi Arabia] (IAFU), McGovern Medical School [Houston, TX, USA] (McGMS), The University of Texas Health Science Center at Houston (UTHealth), Cooper Medical School of Rowan University [Camden] (CMSRU), Airlangga University [Jawa Timur, Indonesia] (AU), University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), Geneva University Hospitals and Geneva University, Universidade de São Paulo = University of São Paulo (USP), Beth Israel Lahey Health [Burlington, MA, USA] (BILH), New York University School of Medicine (NYU Grossman School of Medicine), Memorial Neuroscience Institute [Pembroke Pines, FL, USA] (MNI), Iwate Prefectural Central Hospital [Morioka, Iwate, Japan] (IPCH), Japanese Red Cross Musashino Hospital [Tokyo], Ajou University, University of Ottawa [Ottawa], Saga-ken Medical Centre Koseikan [Saga, Japan] (SMCK), University of South Alabama, Konkuk University [Seoul], Royal Free Hospital [London, UK], Hospital Clinico Universitario de Valladolid [Castilla y León, Spain] (HCUV), Universidad de Valladolid [Valladolid] (UVa), Instituto de Ciencia de Materiales de Aragón [Saragoza, España] (ICMA-CSIC), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Hospital Clínic de Barcelona [Catalonia, Spain], Centro Hospitalar Universitário de São João [Porto], Christchurch Hospital [Christchurch, New Zealand] (CH), University Hospital Basel [Basel], University of Southern California (USC), Kohnan Hospital - Sendai [Miyagi, Japan], University of Texas Southwestern Medical Center [Dallas], Nara City Hospital [Nara, Japan] (NCH), Toyonaka Municipal Hospital [Osaka, Japan] (TMH), Kagoshima City Hospita [Kagoshima, Japan] (KCH), Texas Tech University System [Lubbock, TX, USA] (TTUS), University of Saskatchewan [Saskatoon] (U of S), National Institute of Information and Communications Technology [Tokyo, Japan] (NICT), Royal Prince Alfred Hospital [Camperdown, Australia] (RPAH), Banner Desert Medical Center [Mesa, AZ, USA] (BDMC), Japanese Red Cross Matsue Hospital [Shimane, Japan] (JRCMH), Shiroyama Hospital [Osaka, Japan] (SH), Niigata City General Hospital [Niigata, Japan] (NCGH), Sugimura Hospital [Kumamoto, Japan] (SH), Kawasaki Medical School [Kurashiki, Japan] (KMS), Osaka Red Cross Hospital [Osaka, Japan] (ORCH), Université de Tsukuba = University of Tsukuba, Saiseikai Central Hospital [Tokyo, Japan] (SCH), Kinikyo Chuo Hospital - Sapporo [Hokkaido, Japan] (KCHS), NTT Medical Center Tokyo [Tokyo, Japan] (NTTMCT), Yokohama Shintoshi Neurosurgical Hospital [Yokohama, Japan]. (YSNH), Osaka General Medical Center [Osaka, Japan] (OGMC), University of Miami Leonard M. Miller School of Medicine (UMMSM), Bon Secours Mercy Health System [Toledo, OH, USA] (BSMHS), Maoming City Hospital [Guandong, China] (MCH), Miami Cardiac & Vascular Institute [Miami, FL, USA] (MC&VI), Hackensack University Medical Center [Hackensack], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), University of Tennessee [Chattanooga] (UTC), The University of Texas at San Antonio (UTSA), Mianyang 404 Hospital [Sichuan, China] (M404H), Siriraj Hosital - Mahidol University [Bangkok, Thailand] (SHMU), SUNY Upstate Medical University, State University of New York (SUNY), Royal North Shore Hospital (RNSH), The University of Texas Rio Grande Valley [Harlingen, TX, USA] (UTRGV), Khoula Hospital [Muscat, Oman] (Ministry of Health - KH), University of Michigan [Ann Arbor], University of Michigan System, University of South Florida [Tampa] (USF), Henry Ford Health System [Detroit, MI, USA] (HFHS), Metropolitan Hospital [Piraeus, Greece] (MH), National and Kapodistrian University of Athens (NKUA), Maine Medical Center, Dartmouth Hitchcock Medical Center [Lebanon, NH, USA] (DHMC), Centro Universitário Feevale (BRAZIL), The Valley Hospital [Ridgewood, NJ, USA] (TVH), St Joseph's University Medical Center [Paterson, NJ, USA] (StJUMC), Christian Medical College and Hospital Ludhiana [Punjab, India] (CMCHL), Universidad del Desarrollo, University Graduate School of Medicine [Osaka, Japan], Tokushima University, Universidade Federal de São Paulo, Istanbul Aydin University [İstanbul, Turkey] (IAU), Swedish Medical Center [Englewood, CO, USA] (SMC), Bayhealth Medical Center [Dover, DE, USA] (BMC), Saiseikai Fukuoka General Hospital [Fukuoka, Japan] (SFGH), Osaka Rosai Hospital - Sakai [Osaka, Japan] (ORHS), King Saud University [Riyadh] (KSU), Mount Sinai Health System, University of Calgary, Huzhou University [Zhejiang], The Affiliated Hospital of Southwest Medical University - Luzhou [Sichuan, China] (TAHSMUL), Yijishan Hospital of Wannan Medical College [Wuhu, Anhui, China] (YHWMC), University of Toledo, WellStar Health System [Marietta, GA, USA] (WHS), Institut National de la Recherche Scientifique [Québec] (INRS), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), SVIN COVID-19 Registry, the Middle East North Africa Stroke and Interventional Neurotherapies Organization (MENA-SINO), Japanese Society of Vascular and Interventional Neurology Society (JVIN), University of California [San Francisco] (UCSF), University of California, Yale University School of Medicine, University of São Paulo (USP), and University of California-University of California
Subjects: [SDV]Life Sciences [q-bio], COVID-19, Subarachnoid Hemorrhage* / diagnostic imaging, 030204 cardiovascular system & hematology, Intracranial Aneurysm* / therapy, lcsh:RC346-429, 0302 clinical medicine, Pandemic, Myocardial infarction, Prospective Studies, Stroke, Original Research, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Intracranial Aneurysm* / diagnostic imaging, Cardiology, Subarachnoid haemorrhage, haemorrhage, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Subgroup analysis, subarachnoid, Intracranial Aneurysm* / epidemiology, 03 medical and health sciences, Aneurysm, Internal medicine, medicine, Humans, coil, cardiovascular diseases, Pandemics, lcsh:Neurology. Diseases of the nervous system, Retrospective Studies, business.industry, SARS-CoV-2, Intracranial Aneurysm, Subarachnoid Hemorrhage, medicine.disease, infection, nervous system diseases, Mechanical thrombectomy, Cross-Sectional Studies, aneurysm, Neurology (clinical), Subarachnoid Hemorrhage* / epidemiology, business, 030217 neurology & neurosurgery
Abstract: BackgroundDuring the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study’s objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.MethodsWe conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March–31 May 2020. The prior 1-year control period (1 March–31 May 2019) was obtained to account for seasonal variation.FindingsThere was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI −24.3% to −20.7%, pInterpretationThere was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
Published: 2021
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6. Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

Author: John Hardy, Nick C. Fox, Lena Lilius, Christine Van Broeckhoven, Mindy J. Katz, Carlos Cruchaga, Joshua W. Miller, Carol Brayne, Letizia Concari, Christopher Shaw, Minerva M. Carrasquillo, Richard Mayeux, Anne Boland, Charles DeCarli, Helena C. Chui, Laura B. Cantwell, Yoland Aladro Benito, Chuang Kuo Wu, Elaine R. Peskind, Andrew McDavid, M. Ilyas Kamboh, Amanda Smith, Pascual Sánchez-Juan, Jean-François Deleuze, Jayanadra J. Himali, Thomas H. Mosley, Thomas J. Montine, Chuanhai Cao, Andreas J. Forstner, Thomas G. Beach, Robert Barber, Miquel Aguilar, Liming Qu, Jerome I. Rotter, Matthew J. Huentelman, Christiane Reitz, Christopher J. O'Donnell, Steven G. Younkin, Bradley T. Hyman, Bruce L. Miller, Rachelle S. Doody, Eric B. Larson, Ronald L. Hamilton, Todd E. Golde, Steven E. Arnold, Melissa E. Garcia, Rachel Raybould, Lena Kilander, Mark A. Sager, Kevin Morgan, Kathryn L. Lunetta, William Perry, Joseph D. Buxbaum, Craig S. Atwood, Thomas D. Bird, Michael Conlon O'Donovan, Robert Olaso, Juan Fortea, Susanne Moebus, Lisa L. Barnes, Rachel Marshall, Huntington Potter, Mercè Boada, Shahzad Ahmad, Paolo Caffarra, Daniel C. Marson, Jonathan L. Haines, Perrie M. Adams, John M Olichney, Lars Lannfelt, Stefanie Heilmann-Heimbach, Markus M. Nöthen, Shubhabrata Mukherjee, John Malamon, Xue Wang, Christopher S. Carlson, Karen Ritchie, Roger N. Rosenberg, Paul K. Crane, Alexa S. Beiser, Céline Bellenguez, Robert C. Green, Maria Urbano, Petra Proitsi, John Powell, Elisa Majounie, Ammar Al-Chalabi, Hakon Hakonarson, Yogen Patel, Martin Scherer, Julie Williams, Richard B. Lipton, Vincent Dermecourt, Adam L. Boxer, Gerard D. Schellenberg, David G. Clark, Anita L. DeStefano, Joel H. Kramer, Victoria Alvarez, Nandini Badarinarayan, Oscar L. Lopez, Chris Corcoran, Ubaldo Bonuccelli, Donald R. Royall, James Bowen, Monica Diez Fairen, Tricia A. Thornton-Wells, Nilufer Ertekin-Taner, Florence Pasquier, Martin Ingelsson, Yi Zhao, John R. Gilbert, Valentina Escott-Price, Amanda B. Kuzma, Fabienne Garzia, Reinhard Heun, Otto Valladares, Andrew J. Saykin, Sara Ortega-Cubero, Liana G. Apostolova, Henry L. Paulson, John K Kauwe, Imelda Barber, Carolina Ceballos Diaz, Douglas Galasko, M. Arfan Ikram, Lluís Tárraga, Carlo Caltagirone, Joan S. Reisch, Wolfgang Maier, Bruno Vellas, Rebecca Sims, Angela Hodges, Matthew P. Frosch, Isabel Henández, Annakaisa Haapasalo, Thor Aspelund, Håkan Thonberg, Aimee Pierce, Roger L. Albin, Wayne W. Poon, Rebecca Sussams, Amy Braddel, Ranjan Duara, Albert V. Smith, Kirk C. Wilhelmsen, Gianfranco Spalletta, Simon Lovestone, Peter Passmore, Ana Frank-García, Cynthia M. Carlsson, Jade Chapman, Nathan D. Price, Philip L. De Jager, John M. Ringman, Seung Hoan Choi, Nicola Denning, Michael John Owen, Clinton T. Baldwin, Amalia C. Bruni, Denis A. Evans, Rudolph E. Tanzi, Dominique Campion, Laura Fratiglioni, Alberto Lleó, Per Hoffmann, Carole Dufouil, Charlotte Forsell, Alun Meggy, Charlene Thomas, Robert S. Stern, James B. Leverenz, Tatiana Foroud, William W. Seeley, James J. Lah, Brian A. Lawlor, Kenneth B. Fallon, Matthias Riemenschneider, Ryan M. Huebinger, Regina M. Carney, Clinton B. Wright, Didier Hannequin, Deborah Blacker, Anne Kinhult-Ståhlbom, Ekaterina Rogaeva, Andrew P. Lieberman, Bernardino Ghetti, Linda J. Van Eldik, Bernadette McGuinness, Thomas Fairchild, Margaret A. Pericak-Vance, Ashok Raj, Reinhold Schmidt, Ronald C. Petersen, Harald Hampel, María J. Bullido, Steven L. Carroll, Maria Candida Deniz Naranjo, Kathleen A. Welsh-Bohmer, Myriam Fornage, Joseph F. Quinn, Caroline Graff, Claudia L. Satizabal, Patrice L. Whitehead, David Wallon, Christopher Medway, Lindsay A. Farrer, Vilmundur Gudnason, Peter St George-Hyslop, Pau Pastor, Frank Jessen, Erin L. Abner, Johanna Jakobsdottir, Hieab H.H. Adams, Roberta Cecchetti, Walter A. Kukull, Thomas S. Wingo, Michelle K. Lupton, Valur Emilsson, Susan M. McCurry, Simon Mead, Hilkka Soininen, Sandra Weintraub, Amy Gerrish, Lindy E. Harrell, Lina Keller, Jean-Charles Lambert, Denise Harold, Stephen Todd, Wei Gu, Maura Gallo, Najaf Amin, Lenore J. Launer, Eleonora Sacchinelli, Mikko Hiltunen, Cécile Dulary, Eliecer Coto, Xueqiu Jian, Nathalie Fievet, Patrizia Mecocci, Sarah Taylor, Eric Boerwinkle, Maria Serpente, Ronald G. Munger, Ina Giegling, Carlo Masullo, Aoibhinn Lynch, Eliezer Masliah, Anne M. Koivisto, Chang En Yu, Qiong Yang, Benedetta Nacmias, Wayne C. McCormick, Kristelle Brown, Alessio Squassina, Deborah C. Mash, Brian W. Kunkle, Makrina Daniilidou, Alison Goate, David Carrell, Kara L. Hamilton-Nelson, Sandra Barral, Vincent Chouraki, Kristel Sleegers, Frank J. Wolters, Joseph E. Parisi, Iwona Kłoszewska, Ronald C. Kim, Sonia Moreno-Grau, Marina Arcaro, Carmen Muñoz Fernadez, Vernon S. Pankratz, Duane Beekly, Sabrina Pichler, Gislain Septier, Delphine Bacq, Amanda J. Myers, Adam C. Naj, Frank Martiniuk, Sudha Seshadri, Badri N. Vardarajan, Joshua A. Sonnen, M.-Marsel Mesulam, Howard J. Rosen, James T. Becker, Chiara Fenoglio, Ge Li, Alberto Pilotto, Mary Sano, Olivier Hanon, Honghuang Lin, Jean Paul G. Vonsattel, W. T. Longstreth, Daniela Galimberti, David C. Rubinsztein, RoseMarie Brundin, Vilmantas Giedraitis, Christine M. Hulette, Peter Holmans, Martin Dichgans, Maria Vronskaya, Céline Derbois, Michelangelo Mancuso, Constantine G. Lyketsos, Christophe Tzourio, Jacques Epelbaum, Raffaele Maletta, Mariet Allen, Hong-Dong Li, James R. Burke, Rik Vandenberghe, David G. Mann, Bruce M. Psaty, Lawrence S. Honig, Beth A. Dombroski, Erik D. Roberson, Cornelia M. van Duijn, Benjamin Grenier-Boley, Seppo Helisalmi, Jean-François Dartigues, Russell H. Swerdlow, Paola Bossù, Ashley R. Winslow, Elio Scarpini, Lesley Jones, Sebastien Engelborghs, John Q. Trojanowski, Jeffrey Kaye, Jenny Lord, Chiara Cupidi, Janet A. Johnston, Dan Rujescu, Feroze Golamaully, Anne Braae, Rafael Blesa, L. Adrienne Cupples, Dennis W. Dickson, Gail P. Jarvik, David W. Fardo, David H. Cribbs, Michael Gill, Jose Bras, Allan I. Levey, Jennifer Williamson, Rhodri Thomas, John C. Morris, Lei Yu, Debby W. Tsuang, Annette M. Hartmann, John H. Growdon, John Collinge, Claudine Berr, Fernando Rivadeneira, Oliver Peters, Albert Hofman, Frank M. LaFerla, Vivianna M. Van Deerlin, James Uphill, David A. Bennett, Onofre Combarros, Gudny Eiriksdottir, Jeremy D. Burgess, Melanie L. Dunstan, Elizabeth Crocco, Keeley J. Brookes, Robert R. Graham, Lon S. Schneider, Eden R. Martin, Matt Hill, Neill R. Graff-Radford, Joseph T. Hughes, Vincenzo Solfrizzi, Taniesha Morgan, Antonio Ciaramella, Bruno Dubois, Juan C. Troncoso, Paolo Bosco, Jordi Clarimón, Daniel H. Geschwind, Virginia Boccardi, Barry Reisberg, Timothy W. Behrens, Annette L. Fitzpatrick, Salvatore Spina, Alexis Brice, Eileen H. Bigio, Marla Gearing, Jeffrey M. Burns, Carol A. Miller, Marilyn S. Albert, Sven J. van der Lee, Sandro Sorbi, C. Dirk Keene, Daniel Levy, Antonio Daniele, Eric M. Reiman, Paramita Chakrabarty, Oscar Sotolongo-Grau, Helena Schmidt, Francesco Panza, Murray A. Raskind, Rita Guerreiro, Gyungah Jun, Anna Karydas, Markus Leber, Harry V. Vinters, Cory C. Funk, Charles C. White, Jill R. Murrell, Sid E. O'Bryant, Nigel J. Cairns, Josée Dupuis, Ann C. McKee, Julie A. Schneider, Megan L. Grove, Malcolm B. Dick, Bradley F. Boeve, Jennifer A. Brody, Sanjay Asthana, Agustín Ruiz, Stefan Herms, Yuning Chen, David Craig, Neil W. Kowall, Maria Donata Orfei, JoAnn T. Tschanz, Florentino Sanchez Garcia, Manuel Mayhaus, Alfredo Ramirez, James Turton, André G. Uitterlinden, Davide Seripa, Lee-Way Jin, Kelley Faber, Maria C. Norton, Shuo Li, Steven H. Ferris, Steffi G. Riedel-Heller, Joshua C. Bis, Li-San Wang, Johannes Kornhuber, Peter Paul De Deyn, Martin R. Farlow, Randall L. Woltjer, Gary W. Beecham, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Icelandic Heart Association [Kopavogur, Iceland] (IHA), John P. Hussman Institute for Human Genomics [Miami, FL, USA], University of Miami [Coral Gables], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Department of Medicine, University of Washington [Seattle], Dr. John T. Macdonald Foundation [Miami, FL, USA] (Department of Human Genetics), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Genomics [Bonn, Germany] (Institute of Human Genetics), University of Bonn-Institute of Human Genetics [Bonn, Germany], Department of Molecular Genetics, Institut Català de Neurociències Aplicades [Barcelona, Spain], Well Advanced Solutions, Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], The University of Texas Health Science Center at Houston (UTHealth), Columbia University [New York], University of Eastern Finland, Life & Brain Center - Department of Genomics, Rheinische Friedrich-Wilhelms-Universität Bonn, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), John P. Hussman Institute for Human Genomics, Neurobiologie de la Croissance et de la Senescence, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Emmy Noether Project (SFB 833), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Boston University [Boston] (BU), Department of Genomics, Institute for Systems Biology [Seattle, WA, USA], Universitätsklinikum Bonn (UKB), Centre of Excellence for Robotic Vision [Canberra], Australian Research Council [Canberra] (ARC), Neuroscience and Mental Health Research Institute [Cardiff, UK] (School of Medicine), Boston University School of Medicine (BUSM), Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, University of Pennsylvania [Philadelphia], Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Department of Epidemiology and Biostatistics, ERASMUS, Hospital Universitario Doctor Negrín [Las Palmas de Gran Canaria, Spain], Department of Neurodegenerative Diseases, University of Mississippi Medical Center (UMMC), Pathology and Laboratory Medicine [Philadelphia, PA, USA] (Penn Neurodegeneration Genomics Center), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bioinformatics, GlaxoSmithKline, Aging Research Center [Karolinska Institutet] (ARC ), Stockholm University-Karolinska Institutet [Stockholm], University of Nottingham, UK (UON), University of Texas Health Science Center, Department of Neurobiology, Caring Sciences and Society (NVS), University of Bari Aldo Moro (UNIBA), Ageing Group, Centre for Public Health, Queen's University [Belfast] (QUB), Mayo Clinic [Jacksonville], Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Università degli Studi di Perugia (UNIPG), Framingham Heart Study, Boston University [Boston] (BU)-National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), CHU Rouen, Normandie Université (NU), Universidad Autonoma de Madrid (UAM), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), University of Florida [Gainesville] (UF), University of Parma = Università degli studi di Parma [Parme, Italie], Center for Cognitive Disorders AUSL [Parma, Italy], School of Public Health [Boston], Uppsala University, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Xi'an Jiaotong University (Xjtu), Department of Public health and Caring Sciences, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden, Institute of Gerontology and Geriatrics, Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Geriatric Medicine and Metabolic Diseases, Departments of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf [Hamburg, Germany], University of Texas Southwestern Medical Center [Dallas], University of Cologne, Laboratoire d'Etudes et de Recherche en Informatique d'Angers (LERIA), Université d'Angers (UA), Johns Hopkins University (JHU), Universität Leipzig [Leipzig], University of Iceland [Reykjavik], Metacohorts Consortium, Harvard School of Public Health, Catholic University of Rome, Medical University Graz, Baylor College of Medicine (BCM), Baylor University, University of North Texas Health Science Center [Fort Worth], Santa Lucia Foundation (IRCCS), Nextel S.A. [Bilbao], Massachusetts General Hospital [Boston], Department of Pathology and Laboratory Medicine and Indiana Alzheimer disease Center, Indiana University School of Medicine, Indiana University System-Indiana University System, Joint Institute for the Study of the Atmosphere and Ocean (JISAO), Beijing University of Technology, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Saul B. Korey Department of Neurology, Albert Einstein College of Medicine [New York]-Yeshiva University, Utah State University (USU), Fundació per la Recerca Biomèdica i Social Mútua Terrassa [Barcelona, Spain], Hospital Universitario Mutua de Terrassa, Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Department of neurology, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland, Department of neurology, University of Eastern Finland-University Hospital of Kuopio-University of Eastern Finland-University Hospital of Kuopio, Medical University of Łódź (MUL), University of Leicester, MRC Prion Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, University of Milan, Fondazione Istituto di Ricerca e Cura Carattere Scientifico [Rome], Università degli Studi di Roma Tor Vergata [Roma], Saarland University Hospital, Universitat Autònoma de Barcelona (UAB), Regional Neurogenetic Centre [Lamezia Terme, Italy] (CRN - ASP Catanzaro), Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Universidade do Porto, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Experimental and Clinical Pharmacology, St. James Hospital and Trinity College [Dublin, Ireland], School of Medicine [Dublin], Trinity College Dublin, University of Sheffield [Sheffield], Lancaster University, University of Michigan [Ann Arbor], University of Michigan System, David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, University of Wisconsin-Madison, Rush Alzheimer Disease Center [Chicago, IL, États-Unis], Rush University Medical Center [Chicago], Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), School of Engineering [Cardiff], Department of Psychiatry [Pittsburgh], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Northwestern University Feinberg School of Medicine, Mayo Clinic [Rochester], Swedish Medical Center [Seattle, WA, USA], University of California [San Francisco] (UCSF), University of California, Duke University [Durham], University of Kansas Medical Center [Lawrence], Laboratory of Molecular Neuropsychiatry, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Washington University in Saint Louis (WUSTL), University of South Florida [Tampa] (USF), Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Medical University of South Carolina [Charleston] (MUSC), University of Southern California (USC), Los Alamos National Laboratory (LANL), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Neurology Department, University of California, Davis (UCDavis-Neuro), University of California [Davis] (UC Davis), University of California [Irvine] (UCI), Mount Sinai Medical Center, Indiana State University, University of Alabama at Birmingham [ Birmingham] (UAB), University of Kentucky, New York University [New York] (NYU), NYU System (NYU), Department of Medical and Molecular Genetics, Department of Epidemiology and biostatistics, VU University Medical Center [Amsterdam], Emory University [Atlanta, GA], Department of Neurology, University of California-University of California-David Geffen School of Medicine [Los Angeles], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Department of Medical Genetics, HMNC Brain Health, Alzheimer Disease Research Laboratory, Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Laboratoire d'Informatique, Systèmes, Traitement de l'Information et de la Connaissance (LISTIC), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Psychiatry, School of Medicine-Johns Hopkins University and Johns Hopkins Bayview Medical Center, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of neurosciences, University of California [San Diego] (UC San Diego), Department of Physics and Astronomy [Fort Worth], Texas Christian University (TCU), Department of Computer Science [University of California, Davis], Indiana University System, Institute for Aging and Alzheimer’s Disease Research [Fort Worth] (IAADR), Department of Laboratory Medicine and Pathology, Mayo Clinic, Institute for Memory Impairments and Neurological Disorders [Irvine], University of Colorado Anschutz [Aurora], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Keck School of Medicine [Los Angeles], Indiana University [South Bend], Massachusetts General Hospital, Novartis Institutes for Biomedical Research [Cambridge, MA, USA], Departments of Pathology and Laboratory Medicine (Neuropathology) and Neurology, UCLA Medical Center-David Geffen School of Medicine [Los Angeles], University of California-University of California-University of California [Los Angeles] (UCLA), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Institut de Génomique d'Evry (IG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, University of Antwerp (UA), Institute Born-Bunge, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], University of Kuopio, Centre Mémoire de Ressources et de Recherche [Lille-Bailleul] (CMRR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Roger Salengro [Lille], Laboratoire d'Analyse Génomique, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Inserm-U1167, Dpt Gériatrie [CHU Broca], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Neuroépidémiologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Epidemiology, University of Washington, School of Medicine [Los Angeles], Albert Einstein College of Medicine [New York], IdiPAZ - Instituto de Investigación La Paz [Madrid, Spain], Instituto de Física Teórica UAM/CSIC (IFT), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Department of Internal Medicine, University of Central Asturias [Oviedo, Spain], Human Genome Sequencing Center, Baylor College of Medicine, Baylor University-Baylor University, Department of Epidemiology, Erasmus Medical Centre, Translational Genomics Research Institute [Phoenix, AZ, USA], University of Arizona, Banner Alzheimer's Institute [Phoenix, AZ, États-Unis], University of Texas Health Science Center at San Antonio [San Antonio], Mount Sinai School of Medicine, Department of Psychiatry-Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department. of Neurological Sciences, University of Milan, IRCCS Ospedale Maggiore Policlinico, Centre for Research in Neurodegenerative Diseases, VA Puget Sound Health Care System/GRECC [Seattle, WA, USA], University of Pisa - Università di Pisa, Pfizer Worldwide Research and Development [Cambridge, MA, USA], Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt), Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Saarland University [Saarbrücken], University of Bonn, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Cambridge Institute for Medical Research (CIMR), Department of Molecular Neurosciences, Institute of Neurology, UCL, Institute of Psychiatry, Institute of psychiatry, University of British Columbia (UBC), the Clinical Neuroscience Research Group, University of Manchester [Manchester]-Greater Manchester Neurosciences Centre, Aristotle University of Thessaloniki, Memory and Dementia Centre, 3rd Department of Neurology, G. Pa, University of Barcelona, University of Southampton, Department of Psychiatry [Oxford] (POWIC), University of Oxford [Oxford]-The Warneford Hospital, School of Psychology [Cardiff University], Department of Medical Sciences, UCL, Institute of Neurology [London], Washington University School of Medicine, Netherlands Genomics Initiative, Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), School of Medecine, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], School of Life Sciences, Department of Neuroscience, Mayo Clinic Jacksonville, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Clínica Universidad de Navarra [Pamplona], Neurodegenerative Brain Diseases Group, VIB, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University-Medical Research Council, Brigham Young University (BYU), Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, The Gertrude H Sergivesky Center, Columbia University College of Physicians and Surgeons, Genetic Epidemiology Unit, Section of Clinical and Molecular Neurogenetics, Universität zu Lübeck [Lübeck], University of Pennsylvania - Department of Pathology & Laboratory Medecine, Framingham Heart Study [Framingham, MA, USA], ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), European Project: 29845,LSH-ACC-MENTOR, University of Pennsylvania-University of Pennsylvania, Universität Bonn = University of Bonn-Institute of Human Genetics [Bonn, Germany], Universität Leipzig-Universität Leipzig, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), University of Pennsylvania, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Università degli Studi di Perugia = University of Perugia (UNIPG), Universidad Autónoma de Madrid (UAM), Università degli studi di Parma = University of Parma (UNIPR), Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Universität Leipzig, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Yeshiva University- Albert Einstein College of Medicine [New York], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Università degli Studi di Milano = University of Milan (UNIMI), Saarland University Hospital (UKS), Università degli Studi di Firenze = University of Florence (UniFI), Universidade do Porto = University of Porto, University of California (UC)-University of California (UC), University of California [San Francisco] (UC San Francisco), University of California (UC), University of Kansas Medical Center [Kansas City, KS, USA], Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), University of California [Irvine] (UC Irvine), University of Kentucky (UK), University of California (UC)-University of California (UC)-David Geffen School of Medicine [Los Angeles], Department of Computer Science [Univ California Davis] (CS - UC Davis), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), University of Texas Health Science Center at San Antonio [San Antonio, Tx, USA], Universität Bonn = University of Bonn, University of Oxford-The Warneford Hospital, Medical Research Council-Cardiff University, Universität zu Lübeck = University of Lübeck [Lübeck], Epidemiology, Neurology, Gastroenterology & Hepatology, Internal Medicine, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, IRCCS 'Casa Sollievo della Sofferenza', Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (Ciberned), University of Florida [Gainesville], University of Parma, Troubles cognitifs dégénératifs et vasculaires (U1171), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-INSERM, Yeshiva University- Albert Einstein College of Medicine, Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), Autonomous University of Barcelona (UAB), Università degli Studi di Firenze [Firenze], Universidade do Porto [Porto], Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Washington University in St Louis, University of South Florida (USF), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, McGill University, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique (CNRS), Neuropsychiatrie : recherche épidémiologique et clinique, Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Albert Einstein College of Medicine, Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Università Cattolica del S. Cuore - Catholic University of the Sacred Hearth, University of Florence (UNIFI), CIBER de Enfermedades Neurodegenerativas (CIBERNED), Universität zu Lübeck [Lübeck] - University of Lübeck [Lübeck], [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Icahn School of Medicine at Mount Sinai [New York] (MSSM)-Department of Psychiatry, van der Lee, Sven J [0000-0003-1606-8643], Naj, Adam C [0000-0002-9621-2942], Badarinarayan, Nandini [0000-0002-6944-748X], Chouraki, Vincent [0000-0002-4698-1794], Graham, Robert R [0000-0001-7151-4277], Hoffmann, Per [0000-0002-6573-983X], Smith, Albert V [0000-0003-1942-5845], Satizabal, Claudia L [0000-0002-1115-4430], Brody, Jennifer A [0000-0001-8509-148X], Wolters, Frank J [0000-0003-2226-4050], Lupton, Michelle K [0000-0002-7274-7299], Lin, Honghuang [0000-0003-3043-3942], Adams, Hieab H [0000-0003-3687-2508], Giedraitis, Vilmantas [0000-0003-3423-2021], Pasquier, Florence [0000-0001-9880-9788], Chen, Yuning [0000-0002-7358-7055], Bossù, Paola [0000-0002-1432-0078], Ghetti, Bernardino [0000-0002-1842-8019], Yang, Qiong [0000-0002-3658-1375], Aspelund, Thor [0000-0002-7998-5433], Bullido, María J [0000-0002-6477-1117], Rivadeneira, Fernando [0000-0001-9435-9441], Rubinsztein, David C [0000-0001-5002-5263], Al-Chalabi, Ammar [0000-0002-4924-7712], Tsolaki, Magda [0000-0002-2072-8010], De Jager, Philip L [0000-0002-8057-2505], Dickson, Dennis W [0000-0001-7189-7917], Van Broeckhoven, Christine [0000-0003-0183-7665], Ikram, M Arfan [0000-0003-0372-8585], Amouyel, Philippe [0000-0001-9088-234X], Lambert, Jean-Charles [0000-0003-0829-7817], Apollo - University of Cambridge Repository, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Berr, Claudine, Institut de Neurosciences Translationnelles de Paris - - IHU-A-ICM2010 - ANR-10-IAHU-0006 - IAHU - VALID, and Mentoring of LifeSciHealth-Multipliers in the Accession Candidate Countries - LSH-ACC-MENTOR - 29845 - OLD
Subjects: 0301 basic medicine, Linkage disequilibrium, [SDV]Life Sciences [q-bio], Medizin, Sequence Homology, Genome-wide association study, genetics [Alzheimer Disease], metabolism [Microglia], Linkage Disequilibrium, 0302 clinical medicine, genetics [Protein Interaction Maps], genetics [Membrane Glycoproteins], Gene Frequency, Immunologic, genetics [Adaptor Proteins, Signal Transducing], Receptors, genetics [Exome], Odds Ratio, Innate, genetics [Receptors, Immunologic], Exome, Protein Interaction Maps, genetics [Genetic Predisposition to Disease], Receptors, Immunologic, ABI3 protein, human, Genetics, Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Gene Expression Profiling, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Membrane Glycoproteins, Microglia, Phospholipase C gamma, Sequence Homology, Amino Acid, Polymorphism, Single Nucleotide, Adaptor Proteins, Single Nucleotide, 3. Good health, [SDV] Life Sciences [q-bio], Amino Acid, Settore MED/26 - NEUROLOGIA, genetics [Phospholipase C gamma], [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer's disease, Common disease-common variant, Biology, Article, 03 medical and health sciences, ddc:570, medicine, Journal Article, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Polymorphism, Allele frequency, TREM2 protein, human, TREM2, Case-control study, Signal Transducing, Immunity, medicine.disease, R1, Minor allele frequency, genetics [Immunity, Innate], 030104 developmental biology, Human medicine, 030217 neurology & neurosurgery
Abstract: International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 × 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 × 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.
Published: 2017
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7. Historical Perspectives on the Evolution of Spino-Pelvic Fixation and its Implications on Clinical Care A Narrative Review.

Author: von Glinski A, Yilmaz E, Godolias P, Benneker L, Oner FC, Kandziora F, Schroeder G, Schnake K, Dvorak M, Rajasekaran S, El-Sharkawi M, Vaccaro A, Bransford R, Schildhauer TA, and Chapman JR
Abstract: Study Design: Broad narrative review., Objectives: To review and summarize the evolution of spinopelvic fixation (SPF) and its implications on clinical care., Methods: A thorough review of peer-reviewed literature was performed on the historical evolution of sacropelvic fixation techniques and their respective advantages and disadvantages., Results: The sacropelvic junction has been a long-standing challenge due to a combination of anatomic idiosyncrasies and very high biomechanical forces. While first approaches of fusion were determinated by many material and surgical technique-related limitations, the modern idea of stabilization of the lumbosacral junction was largely initiated by the inclusion of the ilium into lumbosacral fusion. While there is a wide spectrum of indications for SPF the chosen technique remains is defined by the individual pathology and surgeons' preference., Conclusion: By a constant evolution of both instrumentation hardware and surgical technique better fusion rates paired with improved clinical results could be achieved., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2025
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8. Improved Pain, Morning Stiffness, and Fatigue With Bimekizumab in Axial Spondyloarthritis: Results From the Phase III BE MOBILE Studies.

Author: Navarro-Compán V, Rudwaleit M, Dubreuil M, Magrey M, Marzo-Ortega H, Mease PJ, Walsh JA, Dougados M, de la Loge C, Fleurinck C, Massow U, Vaux T, Taieb V, and Deodhar A
Subjects: Adult, Female, Humans, Male, Middle Aged, Double-Blind Method, Pain Measurement, Severity of Illness Index, Treatment Outcome, Antirheumatic Agents therapeutic use, Axial Spondyloarthritis complications, Axial Spondyloarthritis drug therapy, Fatigue complications, Fatigue drug therapy, Fatigue etiology, Fatigue physiopathology, Pain complications, Pain drug therapy, Pain etiology, Pain physiopathology
Abstract: Objective: To assess the effect of bimekizumab on pain, morning stiffness, and fatigue in patients with nonradiographic and radiographic axial spondyloarthritis (axSpA) in the phase III BE MOBILE studies (ClinicalTrials.gov: NCT03928704 and NCT03928743)., Methods: Patients were randomized to bimekizumab 160 mg or placebo every 4 weeks; and all patients received bimekizumab from week 16. Patients reported spinal pain, peripheral pain, morning stiffness, and fatigue to week 52. Total and nocturnal spinal pain were each assessed on a 0-10 numerical rating scale (NRS). Individual Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) items (0-10-point NRS) assessed peripheral arthritis pain (question [Q] 3), enthesitis pain/discomfort (Q4), morning stiffness (mean of Q5 and Q6), and fatigue (Q1). Functional Assessment of Chronic Illness Therapy Fatigue subscale score (FACIT-Fatigue) is also reported., Results: At week 16, bimekizumab-treated patients reported lower mean nocturnal spinal pain, total spinal pain, and BASDAI scores (nominal except for nocturnal spinal pain; all P ≤ 0.001), as well as higher FACIT-Fatigue scores (nominal P < 0.05) vs placebo, indicating improved symptom levels. Improvements continued to week 52 in continuous bimekizumab-treated patients and in placebo-bimekizumab switchers. A higher proportion of bimekizumab- vs placebo-randomized patients achieved increasingly stringent thresholds for low spinal and peripheral pain at week 16; this was sustained or improved at week 52. Results were similar for morning stiffness and fatigue. At week 52, over half of patients were considered FACIT-Fatigue responders (≥ 8-point increase in score)., Conclusion: Bimekizumab treatment led to rapid improvements in levels of pain and morning stiffness. Substantial improvements were seen in all domains across the full disease spectrum of axSpA and continued to week 52., (Copyright © 2024 by the Journal of Rheumatology.)
Published: 2025
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9. The 1st GRAPPA International Meeting on Psoriasis and Psoriatic Arthritis - 1º Encontro Internacional do GRAPPA Sobre Psoríase e Artrite Psoriásica.

Author: Goldenstein-Schainberg C, da Silva DLF, Soriano ER, Savage LJ, and Mease PJ
Published: 2025
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10. Janus-kinase inhibitor use in immune-mediated inflammatory diseases beyond licensed indications: A scoping review.

Author: Challoumas D, Simpson C, Arnold M, Mease P, Moots R, Ndosi M, and Locher ZR
Abstract: Introduction: The use of Janus kinase inhibitors (JAKis) in immune-mediated inflammatory diseases (IMIDs) beyond licence is expanding rapidly. The aim of this scoping review was to identify and present the available evidence on the efficacy of JAKis in all conditions without marketing authorisation., Methods: Through a systematic literature search we identified studies including 5 or more patients that assessed the use of any JAKi for any efficacy outcome. Quantitative analyses in the form of pairwise meta-analyses were performed for eligible data from randomised controlled trials (RCTs) only., Results: Eighty-three (n = 83) studies in total were included in our review, assessing efficacy of JAKis in 34 IMIDs. In most conditions, JAKis exhibited generally positive effects, though the majority of evidence came from observational, non-comparative studies. Pairwise meta-analyses were possible for hidradenitis suppurativa and systemic lupus erythematosus (SLE). For hidradenitis suppurativa, we found a clear benefit of treatment with JAKis compared with placebo in achieving clinical response [OR 2.35, 95 % CI (1.24 to 4.46)]. For treatment-resistant SLE, the results were equivocal; JAKi showed some benefit over placebo but statistical significance was only reached for one of the two meta-analysed outcome measures [SLE Responder Index 4, OR 1.41, 95 % CI (1.01 to 1.98); SLE Disease Activity Index 2000; OR 1.36, 95 % CI (0.99 to 1.88)]., Conclusions: There is a rapidly increasing use of JAKis beyond current licencing in most IMIDs. Large comparative trials are necessary to confirm efficacy and guide future licencing decisions., Competing Interests: Declaration of competing interest, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Published: 2024
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11. Kaposi sarcoma herpesvirus Inflammatory Cytokine Syndrome (KICS) - A Severe Complication of an Overlooked Donor-Derived Infection.

Author: Goldman JD and La Hoz RM
Abstract: Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jason D. Goldman reports a relationship with Karius Inc that includes: consulting or advisory. Ricardo La Hoz reports a relationship with Southwest Transplant Alliance that includes: board membership. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Published: 2024
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12. Efficacy and safety of tofacitinib in an open-label, long-term extension study in patients with psoriatic arthritis who received adalimumab or tofacitinib in a Phase 3 randomized controlled study: a post hoc analysis.

Author: Gladman DD, Nash P, Mease PJ, FitzGerald O, Duench S, Cadatal MJ, and Masri KR
Subjects: Humans, Male, Female, Middle Aged, Double-Blind Method, Adult, Treatment Outcome, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors adverse effects, Protein Kinase Inhibitors administration & dosage, Aged, Pyrimidines therapeutic use, Pyrimidines adverse effects, Pyrimidines administration & dosage, Piperidines therapeutic use, Piperidines adverse effects, Piperidines administration & dosage, Arthritis, Psoriatic drug therapy, Adalimumab therapeutic use, Adalimumab adverse effects, Adalimumab administration & dosage, Antirheumatic Agents therapeutic use, Antirheumatic Agents adverse effects, Antirheumatic Agents administration & dosage, Pyrroles therapeutic use, Pyrroles adverse effects, Pyrroles administration & dosage
Abstract: Background: Data on treatment switching directly from tumor necrosis factor inhibitors to tofacitinib in psoriatic arthritis (PsA) are limited. This post hoc analysis assessed efficacy and safety outcomes in patients with PsA who directly switched to tofacitinib in a long-term extension (LTE) study after receiving adalimumab (ADA) in a Phase 3 study, compared with those who continued to receive tofacitinib., Methods: Patients with active PsA received tofacitinib 5 mg twice daily (BID) or ADA 40 mg once every 2 weeks in a 12-month, randomized, double-blind study (OPAL Broaden) and then continued or switched to tofacitinib 5 mg BID and maintained this dose in an open-label LTE study (OPAL Balance). Efficacy was assessed 3 months before the last visit and at the last visit in the Phase 3 study, and at month 3 (or month 6 for select outcomes) in the LTE study and included rates of ≥ 20/50/70% improvement in American College of Rheumatology response criteria, Psoriasis Area and Severity Index ≥ 75% improvement, Health Assessment Questionnaire-Disability Index (HAQ-DI) response (decrease from baseline ≥ 0.35 for patients with baseline HAQ-DI ≥ 0.35), Psoriatic Arthritis Disease Activity Score ≤ 3.2, and minimal disease activity; and change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue score. Safety was assessed at months 3 and 12 in both studies via incidence rates (patients with first events/100 patient-years)., Results: Overall, 180 patients were included (ADA→tofacitinib 5 mg BID: n = 91; continuing tofacitinib 5 mg BID: n = 89). At Phase 3 baseline, patients in the ADA→tofacitinib 5 mg BID group tended to be younger and have less active disease compared with those continuing tofacitinib. Efficacy was similar between groups in the Phase 3 study, and was maintained to month 3 or 6 in the LTE study. Treatment-emergent adverse events (AEs), serious AEs, and serious infections were generally similar in the Phase 3 and LTE studies, and between groups within each study., Conclusion: Tofacitinib efficacy and safety were similar in patients with PsA who directly switched from ADA to tofacitinib and those who continued tofacitinib, suggesting that patients can be directly switched from ADA to tofacitinib without any washout period., Trial Registration: NCT01877668; NCT01976364., Competing Interests: Declarations. Ethics approval and consent to participate: Both studies were conducted in accordance with the Good Clinical Practice guidelines of the International Council for Harmonisation and with the principles of the Declaration of Helsinki. All patients provided written informed consent and the protocols were approved by the institutional review board or independent ethics committee at each investigational site. Consent for publication: Not applicable. Competing interests: DDG has received grants and/or research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB, and has acted as a consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc, and UCB. PN has received grants and/or research support from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer Inc, and UCB, and has received speaker fees/honoraria from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, and Pfizer Inc. PJM has received grants and/or research support from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead Sciences, Janssen, Novartis, Pfizer Inc, Sun, and UCB, has acted as a consultant for AbbVie, Acelyrin, Aclaris, Alumis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead Sciences, Inmagene, Janssen, MoonLake, Novartis, Pfizer Inc, Sun, UCB, and Ventyx, and has received speaker fees/honoraria from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB. OF has received grants and/or research support from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, and UCB, has acted as a consultant for Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and Pfizer Inc, and has received speaker fees/honoraria from AbbVie, Janssen, Novartis, and Pfizer Inc. SD and MJC are employees and stockholders of Pfizer Inc. KRM is a stockholder of Pfizer Inc and was an employee of Pfizer Inc at the time of the analysis., (© 2024. The Author(s).)
Published: 2024
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13. Comparison of On-Label Treatment Persistence in Real-World Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Interleukin-17A Inhibitors.

Author: Mease PJ, Ferrante SA, Shiff NJ, Fitzgerald TP, Chakravarty SD, and Walsh JA
Abstract: Introduction: Psoriatic arthritis (PsA) is a chronic, multidomain, inflammatory disease requiring long-term treatment. Guselkumab, a fully human interleukin [IL]-23p19-subunit inhibitor, and the IL-17A inhibitors (IL-17Ai) ixekizumab and secukinumab are approved by the US Food and Drug Administration (FDA) for adults with active PsA. Real-world data evaluating on-label treatment persistence is an important consideration for patients., Methods: This retrospective claim-based analysis (IQVIA PharMetrics® Plus) included adults with PsA receiving guselkumab or their first subcutaneous (SC) IL-17Ai (ixekizumab/secukinumab) per FDA label ("on-label") between July 14, 2020, and June 30, 2022. Baseline demographic and disease characteristics were collected in the 12 months preceding the index date (date of first guselkumab or SC IL-17Ai claim); follow-up extended through the earlier of the end of continuous insurance eligibility or end of data availability. Baseline characteristics were balanced between the cohorts by propensity score weighting (standardized mortality ratio [SMR]). Discontinuation was defined as a gap 2 × the FDA-approved maintenance dosing interval (guselkumab:112 days; SC IL-17Ai: 56 days); on-label persistence in the weighted cohorts was assessed using Kaplan-Meier curves and compared with a Cox proportional hazards model., Results: Weighted demographic and disease characteristics were well balanced between the cohorts (guselkumab: N = 910, mean age = 50.4 years, 60.4% female; SC IL-17Ai: N = 2740, mean age = 50.2, 59.4% female). At 12 months, the guselkumab cohort was 1.85 × more likely to remain persistent with on-label therapy vs the SC IL-17Ai cohort (p < 0.001); median time to discontinuation was not reached for guselkumab and was 12.3 months for SC IL-17Ai. At 3, 6, 9, and 12 months, persistence rates in the weighted cohorts were higher with guselkumab than with SC IL-17Ai (p < 0.001)., Conclusion: In this real-world claims data analysis in adults with PsA, on-label persistence rates were statistically significantly higher with guselkumab, as early as 3 months, with ~ 2 × greater likelihood of persistence at 12 months relative to SC IL-17Ai., Competing Interests: Declarations. Conflict of interest: Philip J Mease has received consulting fees from AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Immagene, Janssen, Novartis, Pfizer, UCB, and Ventyx; speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB; and research grants from AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, and UCB. Shannon A Ferrante, Natalie J Shiff, Timothy P Fitzgerald, and Soumya D Chakravarty are or were employees of Janssen Scientific Affairs, LLC, a Johnson & Johnson company at the time this work was performed and own stock in Johnson & Johnson. Natalie J Shiff also owns stock in or has owned stock in AbbVie, Gilead, Iovance, Novo-Nordisk, and Pfizer within the past 3 years and is currently an employee of Alpine Immune Sciences, A Vertex Company. Jessica A Walsh has received consulting fees for AbbVie, Eli Lilly, Janssen, Novartis, and UCB; and research funding from AbbVie, Merck, and Pfizer. Ethical approval: The IQVIA PharMetrics® Plus database, used under license for this study, complies with Health Insurance Portability and Accountability Act (HIPAA) regulations. The data obtained from these analyses were de-identified; thus, no Institutional Review Board approval was required., (© 2024. The Author(s).)
Published: 2024
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14. Guselkumab in Biologic-Naïve Patients with Active Psoriatic Arthritis in Russia: A Post Hoc Analysis of the DISCOVER-1 and -2 Randomized Clinical Trials.

Author: Mease P, Korotaeva T, Shesternya P, Kokhan M, Rukavitsyn A, Vasilchenkov D, Sharaf M, Lavie F, and Deodhar A
Abstract: Introduction: There are limited data on the use of advanced therapies to treat psoriatic arthritis (PsA) in Russia. Guselkumab, an interleukin (IL)-23p19-subunit inhibitor, demonstrated efficacy in patients with PsA in the phase 3 DISCOVER-1 and -2, and COSMOS trials. This analysis evaluated the efficacy and safety of guselkumab in patients with PsA in Russia., Methods: This post hoc analysis of DISCOVER-1 and -2 included 1002 biologic-naïve patients with active PsA from Russia (n = 317) and the rest of the world (RoW; n = 685). Patients received guselkumab 100 mg every 4 weeks (Q4W), or at week 0 and 4 then Q8W, or placebo then guselkumab Q4W at week 24 (Russian: n = 119, 88, and 110, respectively; RoW: n = 216, 246, and 223, respectively). Outcomes through week 52 were pooled (DISCOVER-1 and -2); outcomes from week 52 to 100 represent DISCOVER-2 only., Results: In patients from Russia, ≥ 20% improvement in the American College of Rheumatology (ACR20) criteria response rates were higher with guselkumab vs. placebo at week 24, increased through week 52, and were consistent across all guselkumab-treated groups at week 100. Similar trends were generally observed for ACR50, ≥ 90% improvement in Psoriasis Area and Severity Index (PASI90), achievement of Disease Activity in Psoriatic Arthritis (DAPSA) low disease activity/remission and minimal disease activity, enthesitis and dactylitis resolution, ≥ 0.35 improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI) score, improvement in patient-reported pain, and measures in patients with axial PsA (including Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS], and patient-reported spinal pain). Efficacy responses were similar between patients from Russia and the RoW across all endpoints and timepoints. The safety profile of guselkumab in patients from Russia was consistent with previous findings., Conclusion: This analysis demonstrated that the safety and efficacy profiles of guselkumab across all PsA domains and patient-reported outcomes in patients from Russia were similar to those in patients from the RoW., Trial Registration Numbers: NCT03162796 and NCT03158285., Competing Interests: Declarations Conflict of Interest Philip Mease: Research grants from AbbVie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, SUN, and UCB; consulting fees from AbbVie, Acelyrin, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Immagene, Janssen, Novartis, Pfizer, SUN, UCB, and Ventyx; and speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Tatiana Korotaeva: Consulting fees from Biocad, Janssen, Novartis, and Swixx; research grant funding from Pfizer; and speaker fees from AbbVie, Biocad, Janssen, and Novartis. Pavel Shesternya: Consulting and speaker fees from AbbVie, Biocad, Janssen, Novartis, Pfizer, and R-Pharm. Muza Kokhan: Consulting fees from Celgene, Johnson & Johnson, and Novartis; grant/research support from AbbVie, Celgene, Eli Lilly, Galderma, Johnson & Johnson, LEO Pharma, MSD, Novartis, Pfizer, and UCB; and speaker fees from AbbVie, Celgene, Eli Lilly, Galderma, Johnson & Johnson, Novartis, and UCB. Anton Rukavitsyn: Employee of Johnson & Johnson LLC, Russian Federation. Dmitry Vasilchenkov: Employee of Johnson & Johnson LLC, Russian Federation. Mohamed Sharaf: Employee of Johnson & Johnson EMEA, United Arab Emirates. Frédéric Lavie: Employee of Pharmaceutical Companies of Johnson & Johnson, France. Atul Deodhar: Consulting fees for participation in advisory boards from AbbVie, Bristol Myers Squibb, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB; research grant funding from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, MoonLake, Novartis, Pfizer, and UCB; and speaker fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Ethical Approval DISCOVER-1 and -2 were conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. The study protocols were approved by ethics committees at each site. All participants provided written informed consent., (© 2024. The Author(s).)
Published: 2024
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15. Persistent Patient-Level Effect of Guselkumab at Consecutive 8-Week Dosing Visits and Over Time in Patients With Active Psoriatic Arthritis: Post Hoc Analysis of a 2-Year, Phase 3, Randomized, Controlled Study.

Author: Mease PJ, Baraliakos X, Chandran V, Soriano ER, Nash P, Deodhar A, Rampakakis E, Shiff NJ, Chakravarty SD, Shawi M, Merola JF, and McInnes IB
Abstract: Objective: Group-level analyses from the phase 3 DISCOVER-2 trial of guselkumab demonstrated robust and durable improvements across psoriatic arthritis (PsA) domains. To specifically evaluate continuous disease control in individual patients, persistence of clinically relevant improvements was assessed, both at consecutive guselkumab dosing visits and over time., Methods: Post hoc analyses included biologic-naïve patients randomized to 100 mg of guselkumab at week 0, week 4, and then every 8 weeks (Q8W). Improvements in joint (minimal clinically important improvement [MCII] in Disease Activity Index for PsA [DAPSA; ≥7.25], clinical DAPSA [cDAPSA; ≥5.7]), skin (Investigator's Global Assessment [IGA] 0/1), and overall disease activity (patient global assessment of arthritis and psoriasis [PtGA Arthritis+Psoriasis; MCII ≥ 15 mm], PsA Disease Activity Score [PASDAS; MCII ≥ 0.8]) were assessed. Proportions of patients with maintenance of DAPSA and cDAPSA MCII at consecutive Q8W guselkumab dosing visits (ie, at weeks 4 and 12, weeks 12 and 20, etc through week 52) and patient-level durability of response through week 100 (Kaplan-Meier) were determined., Results: Among 248 patients randomized to guselkumab Q8W, 93% to 99% maintained clinical improvement in joint disease at consecutive Q8W dosing visits through week 52 across time periods. Among guselkumab patients achieving MCII by week 24, estimated probabilities of maintenance of clinical improvement 100 weeks post achievement ranged from 68% (IGA 0/1) to 89% (PASDAS MCII). Median times to loss of improvement were not reached; estimated mean weeks of maintenance of improvement were 58.6, 52.4, 75.7, 83.6, and 76.7, respectively, for DAPSA, cDAPSA, IGA, PtGA Arthritis+Psoriasis, and PASDAS., Conclusion: Guselkumab provided highly durable patient-level improvements, both at consecutive Q8W dosing visits for joint disease activity and over time across PsA domains according to physician- and patient-driven assessments., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Published: 2024
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16. Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial.

Author: Sise ME, Santos JR, Goldman JD, Tuttle KR, Teixeira JP, Seibert AF, Koullias Y, Llewellyn J, Regan S, Zhao Y, Huang H, Hyland RH, Osinusi A, Winter H, Humeniuk R, Hulter HN, Gottlieb RL, Fusco DN, Birne R, Stancampiano FF, Libertin CR, Small CB, Plate M, and McPhail MJ
Subjects: Humans, Male, Female, Middle Aged, Double-Blind Method, Aged, Acute Kidney Injury chemically induced, Adult, Treatment Outcome, Respiration, Artificial, Aged, 80 and over, Alanine analogs & derivatives, Alanine therapeutic use, Alanine pharmacokinetics, Alanine adverse effects, Adenosine Monophosphate analogs & derivatives, Adenosine Monophosphate therapeutic use, Adenosine Monophosphate adverse effects, Adenosine Monophosphate pharmacokinetics, Adenosine Monophosphate administration & dosage, COVID-19 Drug Treatment, Antiviral Agents therapeutic use, Antiviral Agents adverse effects, Antiviral Agents pharmacokinetics, SARS-CoV-2, COVID-19 complications, COVID-19 mortality, Hospitalization
Abstract: Background: Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment., Methods: In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60., Results: Although enrollment concluded early, 243 participants were enrolled and treated (remdesivir, n = 163; placebo, n = 80). At baseline, 90 participants (37.0%) had acute kidney injury (remdesivir, n = 60; placebo, n = 30), 64 (26.3%) had chronic kidney disease (remdesivir, n = 44; placebo, n = 20), and 89 (36.6%) had kidney failure (remdesivir, n = 59; placebo, n = 30); and 31 (12.8%) were vaccinated against COVID-19. Composite all-cause mortality or invasive mechanical ventilation rates through day 29 were 29.4% and 32.5% in the remdesivir and placebo group, respectively (P = .61). Treatment-emergent adverse events were reported in 80.4% for remdesivir versus 77.5% for placebo, and serious adverse events in 50.3% versus 50.0%, respectively. Pharmacokinetic plasma exposure to remdesivir was not affected by kidney function., Conclusions: Although the study was underpowered, no significant difference in efficacy was observed between treatment groups. REDPINE demonstrated that remdesivir is safe in patients with COVID-19 and severe kidney impairment., Clinical Trials Registration: EudraCT 2020-005416-22; Clinical Trials.gov NCT04745351., Competing Interests: Potential conflicts of interest . M. E. S. received research funding from Gilead Sciences, EMD Serono, AbbVie, Angion, Novartis, Merck, Cabaletta Bio, and Otsuka; served as a scientific advisory board member for Travere, Novartis, Vera Therapeutics, Calliditas, and Mallinckrodt; and served as a data and safety monitoring board member for Alpine Immunoscience. J. R. S. received research funding, consulting fees, and lecture sponsorships from and served on advisory boards for Gilead Sciences, GSK, Janssen-Cilag, Bristol Myers Squibb, ViiV Healthcare, and Merck Sharp & Dohme (MSD). J. D. G. consulted for Gilead Sciences, Eli Lilly, GSK, and Karius; received research support or grants from Gilead Sciences, Eli Lilly, Regeneron, and MSD (Biomedical Advanced Research and Development Authority); and received nonfinancial support from Adaptive Biotechnologies, Monogram Biosciences, and Labcorp (outside the current study). J. P. T. is a consultant for Outset Medical and owns stock and/or stock options in Novo Nordisk A/S. Y. K., J. L., S. R., Y. Z., H. H., R. H. H., A. O., and H. W. are stockholders and employees of Gilead Sciences. R. H. is a former employee and stockholder of Gilead Sciences. H. N. H. received consulting fees from Gilead Sciences. R. L. G. served as a consultant for AbbVie, AstraZeneca, Eli Lilly, GSK, Gilead Sciences, Johnson & Johnson, Roivant Sciences, and Roche Pharmaceuticals; served as a national coordinating primary investigator for Johnson & Johnson; served on an academic steering committee for Roivant Sciences; received from Gilead Sciences a gift in kind to Baylor Scott & White Research Institute to facilitate NCT03383419; owns de minimis stock in AbCellera Biologics; and served as a speaker for Pfizer, outside the scope of coronavirus disease 2019 (COVID-19). D. N. F. served on a Gilead Sciences advisory board, outside the scope of COVID-19, and served as a site primary investigator for clinical trials with Gilead Sciences, Regeneron, and MetroBiotech. R. B. served on a scientific advisory board for AstraZeneca, Bayer, Boehringer Ingelheim, MSD, and Mundipharma; and served as a speaker for AstraZeneca, Bayer, MSD, Mundipharma, and Gilead Sciences, outside the scope of COVID-19. C. B. S. has received research support from Gilead Sciences, MSD, GSK, Takeda, Shire, Janssen, AbbVie, and ViiV Healthcare. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Published: 2024
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17. Reduced Likelihood of Hospitalization With the JN.1 or HV.1 Severe Acute Respiratory Syndrome Coronavirus 2 Variants Compared With the EG.5 Variant.

Author: Levy ME, Chilunda V, Davis RE, Heaton PR, Pawloski PA, Goldman JD, Schandl CA, McEwen LM, Cirulli ET, Wyman D, Rossi AD, Dai H, Isaksson M, Washington NL, Basler T, Tsan K, Nguyen J, Ramirez J, Sandoval E, Lee W, Lu J, and Luo S
Subjects: Humans, Male, Middle Aged, Female, Adult, Aged, COVID-19 virology, COVID-19 epidemiology, SARS-CoV-2 genetics, Hospitalization statistics & numerical data
Abstract: Within a multistate viral genomic surveillance program, we evaluated whether proportions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections attributed to the JN.1 variant and to XBB-lineage variants (including HV.1 and EG.5) differed between inpatient and outpatient care settings during periods of cocirculation. Both JN.1 and HV.1 were less likely than EG.5 to account for infections among inpatients versus outpatients (adjusted odds ratio [aOR], 0.60 [95% confidence interval (CI), .43-.84; P = .003] and 0.35 [.21-.58; P < .001], respectively). JN.1 and HV.1 variants may be associated with a lower risk of severe illness. The severity of coronavirus disease 2019 may have attenuated as predominant circulating SARS-CoV-2 lineages shifted from EG.5 to HV.1 to JN.1., Competing Interests: Potential conflicts of interest . M. E. L., V. C., L. M. M., E. T. C., D. W., A. D. R., H. D., M. I., N. L. W., T. B., K. T., J. N., J. R., E. S., W. L., J. L., and S. L. are employees of Helix. M. E. L., E. T. C., D. W., M. I., J. L., and S. L. report support for attending meetings and/or travel from Helix. M. E. L., E. T. C., D. W., A. D. R., M. I., N. L. W., W. L., J. L., and S. L. report stock or stock options from Helix. M. E. L., M. I., W. L., and S. L. report contracted research from Pfizer. M. E. L., M. I., W. L., and S. L. report contracted research from the Centers for Disease Control and Prevention. M. E. L. reports contracted research and travel support from Novavax. R. E. D. reports consulting fees from Health Advances. P. R. H. reports contracted research from Seegene USA and Helix. J. D. G. reports contracted research from Helix, Gilead, Eli Lilly, and Regeneron; grants from Merck (BARDA) and Gilead; speaking honoraria and personal fees from Gilead Sciences and Eli Lilly; and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences, and LabCorp; and service as a speaker or advisory board member for Gilead and Eli Lilly. C. A. S. reports giving educational lectures sponsored by Eli Lilly. M. I., N. L. W., and S. L. report patents pending or issued to Helix (M. I. and S. L.: US-11776694-B2 and US-20230178236-A1). P. A. P. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2024
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18. Association of achieving clinical disease control criteria and patient-reported outcomes in bimekizumab-treated patients with active psoriatic arthritis: results from two phase III studies.

Author: Kristensen LE, Tillett W, Nash P, Coates LC, Mease PJ, Ogdie A, Gisondi P, Ink B, Prickett AR, Bajracharya R, Taieb V, Lyris N, Lambert J, and Walsh JA
Abstract: Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease that causes pain and fatigue, reduces physical function, and negatively impacts health-related quality of life (HRQoL). In the phase III BE OPTIMAL and BE COMPLETE studies, bimekizumab demonstrated clinical efficacy and meaningful improvements in patient-reported outcome (PRO) measures in biologic disease-modifying antirheumatic drug (bDMARD)-naïve patients, and those who had prior inadequate response/intolerance to tumor necrosis factor inhibitors (TNFi-IR)., Objectives: To examine the association between achieving increasingly stringent clinical disease control criteria and improvements in PRO measures in patients with active PsA receiving bimekizumab., Design: Post hoc analysis of two phase III studies., Methods: BE OPTIMAL and BE COMPLETE assessed subcutaneous bimekizumab 160 mg every 4 weeks in bDMARD-naïve and TNFi-IR patients with active PsA. Disease control was assessed using American College of Rheumatology (ACR) response criteria, Minimal Disease Activity, Disease Activity Index for Psoriatic Arthritis, and the composite outcome of ACR50 and 100% improvement in Psoriasis Area and Severity Index. Associations between clinical disease control criteria and PRO measures of pain, fatigue, physical function, and HRQoL were assessed at week 16 and week 52/40 (BE OPTIMAL/BE COMPLETE)., Results: Achievement of increasingly stringent clinical disease control criteria was generally associated with sequentially greater improvements in all PRO measures, including pain. At week 52/40, 94.7% of bDMARD-naïve and 97.6% of TNFi-IR patients achieving ACR70 reported ⩾50% improvements in pain from baseline, and the greatest numerical improvements (-48.5 bDMARD-naïve; -54.7 TNFi-IR). This pattern was evident as early as week 16 and sustained when assessed at week 52/40 across the majority of clinical disease control criteria and PRO measures reported., Conclusion: The achievement of increasingly stringent thresholds of disease control was associated with corresponding greater improvements in PROs, for patients receiving bimekizumab treatment, irrespective of prior TNFi use., Trial Registration Clinicaltrialsgov: NCT03895203, NCT03896581, and NCT04009499., Competing Interests: L.E.K.: At the time of manuscript preparation. L.E.K. was at The Parker Institute, Copenhagen University Hospital, L.E.K. is now an employee of LEO Pharma; Consulting and speaking fees from AbbVie, Amgen, BMS, Biogen, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer and UCB; IIT research grants from AbbVie, Eli Lilly Novartis, Novo, and UCB. W.T.: Research grants, consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, BMS, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ono Pharma, Pfizer, and UCB. P.N.: Grants for research and clinical trials and honoraria for advice and lectures from AbbVie, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Novartis, Pfizer, Samsung, Sanofi, and UCB. L.C.C.: Grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB; consultant for AbbVie, Amgen, BMS, Boehringer Ingelheim, Celgene, Domain, Eli Lilly, Galapagos, Gilead, Janssen, Moonlake Pharma, Novartis, Pfizer, and UCB; speaking fees from AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, medac, Novartis, Pfizer, and UCB. P.J.M.: Research grants from AbbVie, Acelyrin, Amgen, BMS, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma, Takeda, UCB, and Ventyx; speakers’ bureau for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and, UCB. A.O.: Grant/research support from AbbVie, Amgen, Janssen, Novartis, and Pfizer; consultancy fees from AbbVie, Amgen, BMS, Celgene, CorEvitas, Eli Lilly, GSK, Gilead, Janssen, Novartis, Pfizer, Takeda, and UCB. P.G.: Consultancy fees from AbbVie, Abiogen, Almirall, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, MSD, Novartis, Otsuka, Pfizer, Pierre Fabre, Sanofi, and UCB. B.I.: Employee of UCB; shareholder of AbbVie, GSK, and UCB. A.R.P., R.B., V.T., N.L., and J.L.: Employees and shareholders of UCB. J.A.W.: Consultant for/grant support from AbbVie, Amgen, Eli Lilly, Janssen, Merck, Novartis, Pfizer, and UCB., (© The Author(s), 2024.)
Published: 2024
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19. Efficacy and Safety of Bimekizumab in Patients With Psoriatic Arthritis With or Without Methotrexate: 52-Week Results From Two Phase 3 Studies.

Author: McInnes IB, Mease PJ, Tanaka Y, Gossec L, Husni ME, Kristensen LE, Warren RB, Ink B, Bajracharya R, Coarse J, and Gottlieb AB
Abstract: Objective: The objective of this study was to assess 52-week efficacy and safety of bimekizumab in patients with active psoriatic arthritis (PsA) with or without concomitant methotrexate (+/-MTX) treatment at baseline., Methods: We conducted a post hoc analysis of patients in BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug [bDMARD]-naïve), BE COMPLETE (NCT03896581; prior inadequate response or intolerance to tumor necrosis factor inhibitors [TNFi-IR]), and the BE VITAL open-label extension (NCT04009499) study. Patients were randomized to one of the following treatment groups: bimekizumab 160 mg every four weeks, placebo, or a reference drug (adalimumab 40 mg every two weeks; BE OPTIMAL only). From Week 16, placebo-randomized patients received bimekizumab. Missing data were imputed using non-responder imputation, multiple imputation, or worst-category imputation., Results: Through Week 52, similar proportions of bimekizumab-treated patients achieved American College of Rheumatology 50% (ACR50) response criteria for both +MTX and -MTX (BE OPTIMAL: 54.4% +MTX, 54.7% -MTX; BE COMPLETE: 56.3% +MTX, 48.0% -MTX). Similar proportions of bimekizumab-treated patients achieved complete skin clearance (Psoriasis Area and Severity Index 100% [PASI100] response) and minimal disease activity in both +MTX and -MTX groups. Similar trends were seen in placebo/bimekizumab-treated patients. Through Week 52, the proportion of bimekizumab-treated patients with ≥1 treatment-emergent adverse event were similar between the +MTX and -MTX groups (BE OPTIMAL 325 of 410 [79.3%] vs 230 of 292 [78.8%], BE COMPLETE 105 of 168 [62.5%] vs 138 of 220 [62.7%]). The safety profile was comparable between subgroups and consistent with the prior safety profile of bimekizumab., Conclusion: Treatment with bimekizumab demonstrated consistent, sustained efficacy to 52 weeks in bDMARD-naïve and TNFi-IR patients with PsA and was well tolerated, irrespective of concomitant MTX., (© 2024 UCB Pharma and The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Published: 2024
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20. Association Between Achievement of Clinical Disease Control and Improvement in Patient-Reported Outcomes and Quality of Life in Patients With Psoriatic Arthritis in the Phase 3 SELECT-PsA 1 and 2 Randomized Controlled Trials.

Author: Kavanaugh A, Mease P, Gossec L, Ranza R, Tsuji S, Douglas K, Lane M, Lippe R, Mittal M, Gao T, Setty A, Ciecinski S, Aletaha D, and Nash P
Abstract: Objective: We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient-reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA)., Methods: This was a post hoc analysis of 104-week data from the SELECT-PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT-PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs., Results: A total of 1,069 and 317 patients were analyzed for SELECT-PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled., Conclusion: Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target., (© 2024 AbbVie and The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Published: 2024
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21. Effect of apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study.

Author: Østergaard M, Boesen M, Maksymowych WP, Lambert RG, Bubb MR, Kubassova O, Valenzuela G, Reddy J, Colgan S, Klyachkin Y, Deignan C, Zhou Z, Amouzadeh H, and Mease PJ
Abstract: Background: The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE., Methods: MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026)., Findings: Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -2·32 (95% CI -4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast., Interpretation: Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whole-body MRI, as an objective outcome measure in trials in patients with psoriatic arthritis., Funding: Amgen., Competing Interests: Declaration of interests MØ has received research grants from AbbVie, Amgen, BMS, Celgene, Merck, and Novartis; and has received speaker and consultancy fees from AbbVie, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galapagos, Gilead, Hospira, Janssen, Medac, Merck, Novartis, Novo Nordisk, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB. MB has received research grants from AbbVie, Celgene, and Novartis; has received speaker and consultancy fees from AbbVie, Celgene, Eli Lilly, Image Analysis Group, Novartis, Pfizer, and UCB; and owns stock in Image Analysis Group. WPM has received consulting fees from AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB; has received grant and research support from AbbVie, Novartis, Pfizer, and UCB; and is chief medical officer of CARE Arthritis. RGL has received consulting fees from Calyx, CARE Arthritis, and Image Analysis Group. MRB has received research grants from Amgen, BMS, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, and UCB. OK is employed by and owns stock in Image Analysis Group. GV has received grant and research support from Mallinckrodt and Novartis; has received consultancy fees from AbbVie, Alexion, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Esaote, Exagen, Genentech, Gilead, Global Health Living, Horizon, Image Analysis Group, Janssen, Merck, Novartis, Pfizer, Regeneron, Sandoz, Sanofi, and UCB; and is on the speakers' bureau for AbbVie, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Genentech, Horizon, Janssen, Mallinckrodt, Novartis, Pfizer, Pharmacia, Radius, Regeneron, Sanofi, Takeda, and UCB. JR, SC, YK, CD, ZZ, and HA are employed by and own stock in Amgen. PJM has received grant and research support and consultancy fees from AbbVie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, and UCB; has received consultancy fees from Boehringer Ingelheim, and GSK; and is on the speakers' bureau for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Published: 2024
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22. Treatment of early oligoarticular psoriatic arthritis with apremilast: primary outcomes at week 16 from the FOREMOST randomised controlled trial.

Author: Gossec L, Coates LC, Gladman DD, Aelion JA, Vasandani J, Pinter A, Merola JF, Kavanaugh A, Reddy J, Wang R, Brunori M, Klyachkin Y, Deignan C, and Mease PJ
Subjects: Humans, Male, Double-Blind Method, Female, Middle Aged, Treatment Outcome, Adult, Severity of Illness Index, Arthritis, Psoriatic drug therapy, Thalidomide analogs & derivatives, Thalidomide therapeutic use, Anti-Inflammatory Agents, Non-Steroidal therapeutic use
Abstract: Objectives: Oligoarticular psoriatic arthritis (PsA) is frequent but rarely studied. The objective was to assess the efficacy of apremilast in early oligoarticular PsA., Methods: FOREMOST (NCT03747939) was a phase 4 multicentre, randomised, double-blind, placebo-controlled trial. Patients had early (symptom duration ≤5 years) oligoarticular PsA (>1 but ≤4 swollen and >1 but ≤4 tender joints; 2-8 total active joints). Patients were randomised 2:1 to apremilast 30 mg two times per day or placebo for 24 weeks, with an early escape at week 16. The primary endpoint was the proportion of patients at week 16 who achieved minimal disease activity (MDA)-Joints (modification of MDA mandating ≤1 swollen joint and ≤1 tender joint) based on sentinel joints (those affected at baseline) with a combination of non-responder imputation and multiple imputations. Exploratory analysis assessed all joints., Results: Of 308 patients randomised (apremilast: n=203; placebo: n=105), mean (SD) PsA duration was 9.9 (10.2) months, mean (SD) age was 50.9 (12.5) years and 39.9% of patients were using a conventional synthetic disease-modifying antirheumatic drug. MDA-Joints (sentinel joints (primary endpoint) and all joints) were achieved by significantly more patients with apremilast (33.9% and 21.3%) vs placebo (16.0% and 7.9%) at week 16 (p=0.0008 and nominal p=0.0028, respectively). Greater improvements in patient-reported outcomes, clinical disease activity and skin involvement were also seen with apremilast versus placebo., Conclusions: FOREMOST is the first randomised controlled trial designed for early oligoarticular PsA and showed apremilast improves clinical and patient-reported outcomes. This trial may inform the optimal management of PsA in these patients., Trial Registration Number: NCT03747939., Competing Interests: Competing interests: LG has received medical writing support and honoraria as part of advisory boards for this study. Outside this work: grants or contracts from AbbVie, Biogen, Lilly, Novartis and UCB; consulting fees from AbbVie, BMS, Celltrion, Janssen, Novartis, Pfizer and UCB; honoraria for lectures from AbbVie, Amgen, BMS, Celltrion, Janssen, Lilly, MSD, Novartis, Pfizer and UCB; support for attending meetings and/or travel from MSD, Novartis and Pfizer; and medical writing support from AbbVie, Janssen, Galapagos, and UCB. LCC: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene Corporation, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, MoonLake, Novartis, Pfizer, UCB–grant/research support, consulting fees, and/or speaker honoraria. LCC was supported by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre (BRC). DDG: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB–grant/research support or consulting fees. JAA: AbbVie, Amgen–speakers bureau; AbbVie, Ardea Biosciences, AstraZeneca, Bristol Myers Squibb, Celgene, Centocor, Eli Lilly, Galapagos, Genentech, GlaxoSmithKline, Human Genome Sciences, Janssen, Merck, Mesoblast, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi-Aventis, Takeda, UCB, Vertex–grant/research support. JV: Nothing to disclose. AP: AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO-Pharma, Medac, Merck Serono, Mitsubishi, MSD, Novartis, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Schering-Plough, UCB Pharma–investigator/speaker/advisor. JFM: AbbVie, Arena, Avotres, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, EMD, Janssen, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Serono, Sun, UCB–consultant and/or investigator. AK: Amgen, AbbVie, BMS, Janssen, Novartis, Pfizer, Eli Lilly–grant/research support and consultant. JR, RW, MB, YK and CD: Employment by and stock ownership in Amgen. PJM: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun, UCB–grant/research support and consultant; Boehringer Ingelheim, GlaxoSmithKline–consultant; AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB–speakers bureau., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)
Published: 2024
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23. A retrospective multicenter study of operating room extubation and extubation timing after cardiac surgery.

Author: Etchill EW, Wu X, Alejo D, Fonner CE, Ling C, Worrall N, Lehr E, Pagani F, Haber T, Theurer P, Collins-Brandon J, Hira R, Brevig J, Mallory E, Maynard C, Likosky DS, and Whitman GJR
Abstract: Background: In an effort to enhance recovery after cardiac surgery, intraoperative extubation has been targeted as possibly beneficial. This multicenter cohort study aimed to assess this by evaluating the outcomes of operating room (OR) extubation versus extubation within 6 hours of intensive care unit (ICU) arrival (early ICU extubation). Furthermore, we assessed time to ICU extubation and mortality and morbidity., Methods: Patients undergoing on-pump cardiac surgery across 79 hospitals between 2011 and 2020 were included to (1) compare outcomes among OR extubation and early ICU extubation patients and (2) assess time to overall ICU extubation and outcomes., Results: The overall study cohort comprised 163,982 patients, including 95,982 patients (OR extubation: n = 2529 [2.6%] and early ICU extubation: n = 93,453 [97.4%]) who underwent comparison of OR with early ICU extubation. After overlap weighting, patients with OR extubation had longer OR times (5.6 vs 5.1 hours, P < . 0001) and greater rates of reintubation (5.2% vs 2.9%, P = .003), prolonged ventilation (3% vs 2%, P = .021), reoperation for bleeding (1.5% vs 0.7%, P < .01), pneumonia (1.9% vs 1.1%, P < .006), and greater in-hospital mortality on multivariable regression (odds ratio, 1.34, P < .001). Patients with OR extubation at centers with low OR extubation rates (<10%, n = 60) had greater mortality (odds ratio, 1.6, P = .001). Beyond 22 hours of postoperative ICU ventilation, the risk of morbidity and mortality increased significantly., Conclusions: Few patients who undergo cardiac surgery are extubated in the OR, which is associated with no clinical benefit and with increased morbidity. Cardiac surgery programs should reconsider OR extubation after cardiopulmonary bypass. In addition, increased intubation time, in particular >22 hours, is associated with an increase in adverse outcomes., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. Outside of this work, Dr Likosky receives research funding from the Agency for Healthcare Research and Quality and the National Institutes of Health and serves as a consultant for the American Society of Extracorporeal Technology. Dr Likosky and Dr Pagani receive partial salary support from Blue Cross Blue Shield of Michigan to advance quality in Michigan in conjunction with the Michigan Society of Thoracic and Cardiovascular Surgeons Quality Collaborative. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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24. Deucravacitinib, a selective, TYK2 inhibitor, in psoriatic arthritis: Achievement of minimal disease activity components in a phase 2 trial.

Author: Kavanaugh A, Coates LC, Mease PJ, Nowak M, Hippeli L, Lehman T, Banerjee S, and Merola JF
Abstract: Objectives: Deucravacitinib is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor belonging to a distinct class of enzyme inhibitors. In a phase 2 trial in psoriatic arthritis (NCT03881059), deucravacitinib was significantly more efficacious than placebo across multiple endpoints, including achieving minimal disease activity (MDA). This post hoc analysis further evaluated the achievement of individual components of the MDA criteria with deucravacitinib treatment and the time course of responses in the phase 2 trial., Methods: Patients (N = 203) were randomized 1:1:1 to once daily treatment with placebo, deucravacitinib 6 mg, or deucravacitinib 12 mg. The proportions of patients achieving MDA and each of the 7 individual MDA components through week 16 were assessed., Results: At baseline, although some patients met criteria for individual MDA components, none of the patients met the composite MDA criterion, and all components were balanced overall across treatment arms. Treatment with deucravacitinib was associated with a numerically greater mean reduction from baseline in all MDA components vs placebo over 16 weeks of treatment. At week 16, a greater percentage of patients treated with either dose of deucravacitinib vs placebo achieved the threshold criteria for meeting MDA in each of the components., Conclusions: More patients treated with deucravacitinib met each of the MDA components vs placebo, along with a higher rate of MDA response, after 16 weeks of treatment., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Published: 2024
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25. GRAPPA 2023 Collaborative Research Network Meeting.

Author: Chandran V, Gladman DD, Mease PJ, Eder L, Pennington SR, FitzGerald O, Ritchlin C, Webster DE, de Vlam K, and Liao W
Subjects: Humans, Rheumatology methods, Biomedical Research, Arthritis, Psoriatic, Psoriasis
Abstract: The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Collaborative Research Network (CRN)/research committee met during the GRAPPA 2023 annual meeting. Updates were provided on GRAPPA research projects, including the Axial Involvement in Psoriatic Arthritis (AXIS), Axial Psoriatic Arthritis Molecular and Clinical Characterisation Study, Diagnostic Ultrasound Enthesitis Tool (DUET), and Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies (SAGE) studies, as well as the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES) and Elucidating the Landscape of Immunoendotypes in Psoriatic Skin and Synovium (ELLIPSS) studies. The highlight of the meeting was a presentation and discussion on the use of digital tools to study psoriatic disease., (Copyright © 2024 by The Journal of Rheumatology.)
Published: 2024
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26. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) Celebrates Its 20th Anniversary.

Author: Gladman DD, Helliwell PS, and Mease PJ
Subjects: Humans, Anniversaries and Special Events, Biomedical Research history, Dermatology history, Arthritis, Psoriatic diagnosis, Arthritis, Psoriatic history, Psoriasis history, Psoriasis diagnosis, Rheumatology history
Abstract: The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) started in August 2003 with 40 initial participants and celebrated its 20th anniversary with 1036 members, many of whom attended the annual meeting in Dublin, Ireland, on July 15 to 17, 2023. GRAPPA arose from a need experienced by psoriatic arthritis (PsA) and psoriasis (PsO) investigators to meet to address questions related to psoriatic disease (PsD). Though other groups were meeting at the time to classify and discuss PsA, GRAPPA arose from a desire to include international clinical and investigational researchers of both dermatology and rheumatology. The organization has built awareness of PsO and PsA, developed and validated research assessment tools to measure clinical status and disease outcomes, published multiple treatment recommendations, supported basic and clinical research on PsD pathophysiology, fostered interactions across research fields, and educated the future generation of PsO and PsA researchers. The group continues to focus on major priorities affecting patients with PsD and will continue evolving in the next decades., (Copyright © 2024 by The Journal of Rheumatology.)
Published: 2024
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27. Adherence, Persistence, Healthcare Resource Use, and Costs in Tofacitinib-Treated Patients with Psoriatic Arthritis: Data from Two United States Claims Databases.

Author: Mease PJ, Papademetriou E, Potluri R, Agarwal E, Cappelleri JC, and Ling YL
Subjects: Humans, Female, Male, Middle Aged, United States, Adult, Databases, Factual, Antirheumatic Agents therapeutic use, Antirheumatic Agents economics, Health Care Costs statistics & numerical data, Drug Therapy, Combination, Aged, Retrospective Studies, Pyrimidines therapeutic use, Pyrimidines economics, Arthritis, Psoriatic drug therapy, Arthritis, Psoriatic economics, Piperidines therapeutic use, Piperidines economics, Assessment of Medication Adherence
Abstract: Introduction: Associations between increased functional disability and higher healthcare resource utilization (HCRU) and costs were reported in patients with psoriatic arthritis (PsA). We assessed characteristics/outcomes of patients with PsA receiving tofacitinib monotherapy vs combination therapy with conventional synthetic disease-modifying antirheumatic drugs., Methods: Claims data from Optum ® Clinformatics ® Data Mart (OC) and Merative™ MarketScan ® (MS) databases between December 2017 and February 2020 were analyzed. Outcomes assessed were adherence/persistence by therapy type (monotherapy/combination therapy); HCRU/costs (per patient per month) by periods on-treatment (sum time on tofacitinib) and off-treatment (sum time off tofacitinib [gap of > 60 days]) plus therapy type., Results: This analysis included 274 and 395 tofacitinib-treated patients in OC (70.4% female, mean age 54.4 years) and MS (68.9% female, mean age 51.4 years), respectively. Percentages of patients with a proportion of days covered ≥ 0.8 at 12 months for monotherapy vs combination therapy were OC, 44.5% vs 53.8%; MS, 36.4% vs 45.7%. Generally similar trends were seen over 24 months and for medication possession ratio ≥ 0.8. Median (95% confidence interval) times to treatment discontinuation for monotherapy vs combination therapy were OC, 10.1 (7.4-11.8) vs 16.7 (8.3-26.6) months; MS, 6.9 (5.6-9.4) vs 11.0 (6.1-13.9) months. During off-treatment vs on-treatment periods, numerical decreases were observed for all-cause (OC, $5383 vs $6149; MS, $4145 vs $5180) and PsA-related costs (OC, $3237 vs $4515; MS, $2703 vs $3907) regardless of therapy type. During off-treatment vs on-treatment periods, numerical increases in outpatient visits for all-cause (OC, 2.37 vs 2.05; MS, 2.15 vs 1.99) and PsA-related visits (OC, 0.60 vs 0.46; MS, 0.47 vs 0.44) were observed, and PsA-related medications numerically decreased (OC, 1.21 vs 1.53; MS, 1.05 vs 1.48)., Conclusion: In this USA-based claims analysis, tofacitinib adherence was numerically lower for patients with PsA receiving monotherapy vs combination therapy. Costs numerically decreased off-treatment vs on-treatment, irrespective of therapy type, driven by lower medication costs., (© 2024. The Author(s).)
Published: 2024
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28. Impact of Disease Factors of Patients with Psoriasis and Psoriatic Arthritis on Biologic Therapy Switching: Real-World Evidence from the CorEvitas Psoriasis Registry.

Author: Mease PJ, Blauvelt A, Sima AP, Beaty SW, Low R, Gomez B, Gurrola M, and Lebwohl MG
Abstract: Introduction: Patients with psoriasis (PSO) and psoriatic arthritis (PsA) may frequently switch biologic therapies over the course of treatment because of symptom variability and individual responses. Real-world studies analyzing patient characteristics and clinical factors associated with biologic switching are limited., Methods: This longitudinal cohort study used real-world data from the CorEvitas Psoriasis Registry to evaluate the relationship between associated disease factors and biologic switching among patients with PSO and PsA in the United States (US) and Canada following initiation of a biologic. Patients were evaluated between April 2015-August 2022. Combinations of disease severity (as measured by Psoriasis Area Severity Index [PASI]) and Dermatology Life Quality Index (DLQI) as a measure of health-related quality of life (HRQoL) were assessed, and the association with time to switching was calculated using Cox proportional hazards regression modeling., Results: Among 2580 patient-initiations (instances of patients initiating a biologic), 504 (19.5%) switched biologics within 30 months of initiation. Switching was more frequent when either PASI > 10 or DLQI > 5 compared with PASI ≤ 10 or DLQI ≤ 5 at follow-up. Patients with higher skin involvement (PASI > 10) and impact on HRQoL (DLQI > 5) were 14 times more likely to switch (hazard ratio = 14.2, 95% confidence interval: 10.7, 18.9) than those with lower skin involvement (PASI ≤ 10) and HRQoL (DLQI ≤ 5)., Conclusions: Patients with PSO and PsA treated in a real-world dermatology setting with substantial disease factors following biologic initiation were more likely to switch therapies. Those with PASI > 10 and DLQI > 5 switched more frequently than those with PASI ≤ 10 and DLQI ≤ 5., (© 2024. The Author(s).)
Published: 2024
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29. Comparative Effectiveness of Bimekizumab and Ustekinumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

Author: Mease PJ, Warren RB, Nash P, Grouin JM, Lyris N, Taieb V, Eells J, and McInnes IB
Abstract: Introduction: A matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy at 52 weeks (Wk52) of bimekizumab 160 mg every 4 weeks (Q4W) and ustekinumab 45 or 90 mg every 12 weeks (Q12W) in patients with psoriatic arthritis (PsA) who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or who had a previous inadequate response or an intolerance to tumor necrosis factor inhibitors (TNFi-IR)., Methods: Relevant trials were systematically identified. Individual patient data from the bimekizumab trials BE OPTIMAL (NCT03895203; N = 431) and BE COMPLETE (NCT03896581; N = 267) were matched with summary data on patients receiving ustekinumab in the PSUMMIT 1 trial (NCT01009086; 45 mg, N = 205; 90 mg; N = 204) and a subgroup of TNFi-IR patients receiving ustekinumab in the PSUMMIT 2 trial (NCT01077362; 45 mg, N = 60; 90 mg, N = 58), respectively. Patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of the ustekinumab trial patients. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Non-placebo-adjusted comparisons of recalculated bimekizumab and ustekinumab outcomes for the American College of Rheumatology (ACR) 20/50/70 response criteria (non-responder imputation) were analyzed., Results: In patients who were bDMARD naïve, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (odds ratio [95% confidence interval] 45 mg: 2.14 [1.35, 3.40]; 90 mg: 1.98 [1.24, 3.16]), ACR50 (45 mg: 2.74 [1.75, 4.29]; 90 mg: 2.29 [1.48, 3.55]), and ACR70 (45 mg: 3.33 [2.04, 5.46]; 90 mg: 3.05 [1.89, 4.91]). In patients who were TNFi-IR, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (45 mg: 4.17 [2.13, 8.16]; 90 mg: 4.19 [2.07, 8.49]), ACR50 (45 mg: 5.00 [2.26, 11.05]; 90 mg: 3.86 [1.70, 8.79]), and ACR70 (45 mg: 9.85 [2.79, 34.79]; 90 mg: 6.29 [1.98, 20.04])., Conclusions: Using MAIC, bimekizumab showed greater efficacy than ustekinumab in achieving all ACR responses in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52., Trial Registration: NCT03895203, NCT03896581, NCT01009086, NCT01077362., (© 2024. The Author(s).)
Published: 2024
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30. GRAPPA 2023: Major Projects, Key Advances, and Milestones.

Author: Ayan G, Aydin SZ, Coates LC, Eder L, Gladman DD, Helliwell PS, Kaeley GS, Kavanaugh A, Mease PJ, Pennington SR, Proft F, Soriano ER, and FitzGerald O
Subjects: Humans, Rheumatology, Arthritis, Psoriatic drug therapy, Psoriasis therapy
Abstract: At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2023 annual meeting, members were updated on a number of ongoing activities during the key project update session. These activities included the Axial Involvement in Psoriatic Arthritis (AXIS) cohort, the Axial Psoriatic Arthritis Molecular and Clinical Characterization study, the Diagnostic Ultrasound Enthesitis Tool (DUET) study, the Sex- and Gender-Based Analysis of the Effectiveness of Advanced Therapies in Psoriatic Arthritis (SAGE-PsA) study, the Health Initiatives in Psoriasis and Psoriatic Arthritis Consortium European States (HIPPOCRATES), the GRAPPA slide library, and the GRAPPA treatment recommendations., (Copyright © 2024 by The Journal of Rheumatology.)
Published: 2024
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31. Safety and Efficacy of Bimekizumab in Patients with Psoriatic Arthritis: 2-Year Results from Two Phase 3 Studies.

Author: Mease PJ, Merola JF, Tanaka Y, Gossec L, McInnes IB, Ritchlin CT, Landewé RBM, Asahina A, Ink B, Heinrichs A, Bajracharya R, Shende V, Coarse J, and Coates LC
Abstract: Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1 year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2 years., Methods: BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160 mg every 4 weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40 mg every 2 weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE)., Results: A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104 weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100., Conclusions: Bimekizumab was well tolerated for up to 2 years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2 years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms., Trial Registration: BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499)., (© 2024. The Author(s).)
Published: 2024
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32. Comparative Effectiveness of Bimekizumab and Risankizumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

Author: Mease PJ, Warren RB, Nash P, Grouin JM, Lyris N, Willems D, Taieb V, Eells J, and McInnes IB
Abstract: Introduction: The relative efficacy of bimekizumab and risankizumab in patients with PsA who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR) was assessed at 52 weeks (Wk52) using matching-adjusted indirect comparisons (MAIC)., Methods: Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons., Results: In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95% confidence interval]: 1.52 [1.11, 2.09]) and ACR70 (1.80 [1.29, 2.51]). In patients who were TNFi-IR, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR20 (1.78 [1.08, 2.96]), ACR50 (3.05 [1.74, 5.32]), ACR70 (3.69 [1.82, 7.46]), and MDA (2.43 [1.37, 4.32])., Conclusions: Using MAIC, bimekizumab demonstrated a greater likelihood of efficacy in most ACR and MDA outcomes than risankizumab in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52., Trial Registration: NCT03895203, NCT03896581, NCT03675308, NCT03671148., (© 2024. The Author(s).)
Published: 2024
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33. Bimekizumab provided rapid improvements in patient-reported symptoms and health-related quality of life in patients with active psoriatic arthritis: pooled 16-week results from two phase 3 studies.

Author: Husni ME, Mease PJ, Merola JF, Tillett W, Goldammer N, Ink B, Coarse J, Lambert J, Taieb V, and Gladman DD
Subjects: Humans, Male, Female, Middle Aged, Treatment Outcome, Double-Blind Method, Adult, Antirheumatic Agents therapeutic use, Antirheumatic Agents administration & dosage, Severity of Illness Index, Adalimumab therapeutic use, Adalimumab administration & dosage, Fatigue etiology, Quality of Life, Patient Reported Outcome Measures, Arthritis, Psoriatic drug therapy, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized administration & dosage
Abstract: Objectives: To assess impact of bimekizumab treatment on patient-reported outcomes and health-related quality of life (HRQoL) in patients with active psoriatic arthritis (PsA), using 16-week data from two phase 3 studies., Methods: BE OPTIMAL (NCT03895203; biologic disease-modifying antirheumatic drug (bDMARD)-naïve) and BE COMPLETE (NCT03896581; tumour necrosis factor inhibitor inadequate response/intolerance (TNFi-IR)) are phase 3 studies of subcutaneous bimekizumab 160 mg Q4W; both were double-blind and placebo-controlled to 16 weeks. Patients were randomised 3:2:1 to bimekizumab, placebo or reference (subcutaneous adalimumab 40 mg Q2W) in BE OPTIMAL; 2:1 to bimekizumab or placebo in BE COMPLETE. Patient-reported outcomes for pain, fatigue, physical function and HRQoL are reported to week 16 using pooled and individual study data for bimekizumab and placebo patients., Results: 1073/1112 (96.5%) patients completed week 16 (bimekizumab:‍ 677/698 [97.0%]; placebo: 396/414 [95.7%]). Bimekizumab-treated patients achieved rapid improvements vs placebo in pain, fatigue, physical function and HRQoL by week 4, after a single dose. Improvements continued to week 16 for all patient-reported outcomes, including Pain Visual Analogue Scale (VAS; mean (95% CI) change from baseline: bimekizumab: -‍25.2 [-27.2, -23.1]; placebo:‍ -‍5.7 [-8.2, -3.3]) and FACIT-Fatigue (bimekizumab: 4.5 [3.9, 5.1]; placebo: 1.1 [0.3, 2.0]); both nominal p<0.001. Greater proportions of bimekizumab-treated patients achieved minimal clinically important differences for patient-reported symptoms vs placebo, including FACIT-Fatigue (bimekizumab: 53.1%; placebo: 36.3%) and HAQ-DI (bimekizumab:‍ 53.0%; placebo: 28.7%); both nominal p<0.001., Conclusion: Bimekizumab treatment demonstrated rapid and greater improvements in patient-reported pain, fatigue, physical function and HRQoL to week 16 vs placebo in bDMARD-naïve and TNFi-IR patients., Trial Registration Number: ClinicalTrials.gov: NCT03895203; NCT03896581., Competing Interests: Competing interests: MEH: Advisory board member and consultant for AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer and UCB. PJM: Research grants from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Sun Pharma and UCB; consultancy fees from AbbVie, Acelyrin, Aclaris, Amgen, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Moonlake Pharma, Novartis, Pfizer, Sun Pharma and UCB; speakers’ bureau for AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB. JFM: Affiliated with Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA at time of analysis; currently affiliated with UT Southwestern Medical Center, Dallas, TX, USA; consultant and/or investigator for AbbVie, Amgen, Biogen, BMS, Dermavant, Eli Lilly, Janssen, LEO Pharma, Pfizer, Novartis, Regeneron, Sanofi, Sun Pharma and UCB. WT: Research grants, consulting fees, speaking fees, and/or honoraria from AbbVie, Amgen, Celgene, Eli Lilly, GSK, Janssen, MSD, Novartis, Ovo Pharma, Pfizer and UCB. NG, JC, JL: Employees and shareholders of UCB. BI: Employee of UCB; shareholder of AbbVie, GSK and UCB. VT: Employee of UCB. DDG: Consultant and/or received grant support from Abbvie, Amgen, BMS, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2024
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34. Understanding Washington State's Low Uptake of Lung Cancer Screening in Two Steps: A Geospatial Analysis of Patient Travel Time and Health Care Availability of Imaging Sites.

Author: Welch AC, Gorden JA, Mooney SJ, Wilshire CL, and Zeliadt SB
Subjects: Humans, Washington epidemiology, Travel statistics & numerical data, Male, Female, Healthcare Disparities statistics & numerical data, Middle Aged, Mass Screening methods, Spatial Analysis, Lung Neoplasms diagnosis, Lung Neoplasms diagnostic imaging, Lung Neoplasms epidemiology, Early Detection of Cancer statistics & numerical data, Early Detection of Cancer methods, Health Services Accessibility statistics & numerical data
Abstract: Background: Early detection of lung cancer reduces cancer mortality; yet uptake for lung cancer screening (LCS) has been limited in Washington State. Geographic disparities contribute to low uptake, but do not wholly explain gaps in access for underserved populations. Other factors, such as an adequate workforce to meet population demand and the capacity of accredited screening facility sites, must also be considered., Research Question: What proportion of the eligible population for LCS has access to LCS facilities in Washington State?, Study Design and Methods: We used the enhanced two-step floating catchment area (E2SFCA) model to evaluate how geographic accessibility in addition to availability of LCS imaging centers contribute to disparities. We used available data on radiologic technologist volume at each American College of Radiology (ACR)-accredited screening facility site to estimate the capacity of each site to meet potential population demand. Spearman rank correlation coefficients of the spatial access ratios were compared with the 2010 Rural-Urban Commuting Area codes and area deprivation index quintiles to identify characteristics of populations at risk for lung cancer with greater and lesser levels of access., Results: A total of 549 radiologic technologists were identified across the 95 ACR-accredited screening facilities. We observed that 95% of the eligible population had proximate geographic access to any ACR facility. However, when we incorporated the E2SFCA method, we found significant variation of access for eligible populations. The inclusion of the availability measure attenuated access for most of the eligible population. Furthermore, we observed that rural areas were substantially correlated, and areas with greater socioeconomic disadvantage were modestly correlated, with lower access., Interpretation: Rural and socioeconomically disadvantaged areas face significant disparities. The E2SFCA models demonstrated that capacity is an important component and how geographic access and availability jointly contribute to disparities in access to LCS., Competing Interests: Financial/Nonfinancial Disclosures None declared, (Copyright © 2024 American College of Chest Physicians. All rights reserved.)
Published: 2024
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35. Comparison of Real-World On-Label Treatment Persistence in Patients with Psoriatic Arthritis Receiving Guselkumab Versus Subcutaneous Tumor Necrosis Factor Inhibitors.

Author: Walsh JA, Lin I, Zhao R, Shiff NJ, Morrison L, Emond B, Yu LH, Schwartzbein S, Lefebvre P, Pilon D, Chakravarty SD, and Mease P
Abstract: Background: Treatment persistence among patients with psoriatic arthritis (PsA) is essential for achieving optimal treatment outcomes. Guselkumab, a fully human interleukin-23p19-subunit inhibitor, was approved by the United States (US) Food and Drug Administration for the treatment of active PsA in July 2020, with a dosing regimen of 100 mg at week 0, week 4, then every 8 weeks. In the Phase 3 DISCOVER-1 and DISCOVER-2 studies of patients with active PsA, 94% of guselkumab-randomized patients completed treatment through 1 year and 90% did so through 2 years (DISCOVER-2). Real-world evidence is needed to compare treatment persistence while following US prescribing guidelines (i.e., on-label persistence) for guselkumab versus subcutaneous (SC) tumor necrosis factor inhibitors (TNFis)., Methods: Adults with PsA receiving guselkumab or their first SC TNFi (i.e., adalimumab, certolizumab pegol, etanercept, or golimumab) between 14 July 2020 and 31 March 2022 were identified in the IQVIA PharMetrics ® Plus database (first claim defined the treatment start date [index date]). Baseline characteristics and biologic use (biologic-naïve/biologic-experienced) were assessed during the 12-month period preceding the index date. Baseline characteristics were balanced between cohorts using propensity-score weighting based on the standardized mortality ratio approach. The follow-up period spanned from the index date until the earlier of the end of continuous insurance eligibility or end of data availability. On-label persistence, defined as the absence of treatment discontinuation (based on a gap of 112 days for guselkumab or 56 days for SC TNFi) or any dose escalation/reduction during follow-up, was assessed in the weighted treatment cohorts using Kaplan-Meier (KM) curves. A Cox proportional hazards model, further adjusted for baseline biologic use, was used to compare on-label persistence between the weighted cohorts., Results: The guselkumab cohort included 526 patients (mean age 49.8 years; 61.2% female) and the SC TNFi cohort included 1953 patients (mean age: 48.5 years; 60.2% female). After weighting, baseline characteristics were well balanced with a mean follow-up of 12.3-12.4 months across cohorts; 51.5% of patients in the guselkumab cohort and 16.7% in the SC TNFi cohort received biologics in the 12-month baseline period. Respective rates of treatment persistence at 3, 6, 9, and 12 months were 91.2%, 84.1%, 75.9%, and 71.5% for the guselkumab cohort versus 77.3%, 61.6%, 50.0%, and 43.7% for the SC TNFi cohort (all log-rank p < 0.001). At 12 months, patients in the guselkumab cohort were 3.0 times more likely than patients in the SC TNFi cohort to remain persistent on treatment (p < 0.001). Median time to discontinuation was not reached for the guselkumab cohort and was 8.9 months for the SC TNFi cohort., Conclusion: This real-world study employing US commercial health-plan claims data to assess on-label treatment persistence in PsA demonstrated that, at 12 months, guselkumab was associated with a 3 times greater likelihood of persistence compared with SC TNFi., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Published: 2024
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36. Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

Author: Erlandson KM, Geng LN, Selvaggi CA, Thaweethai T, Chen P, Erdmann NB, Goldman JD, Henrich TJ, Hornig M, Karlson EW, Katz SD, Kim C, Cribbs SK, Laiyemo AO, Letts R, Lin JY, Marathe J, Parthasarathy S, Patterson TF, Taylor BD, Duffy ER, Haack M, Julg B, Maranga G, Hernandez C, Singer NG, Han J, Pemu P, Brim H, Ashktorab H, Charney AW, Wisnivesky J, Lin JJ, Chu HY, Go M, Singh U, Levitan EB, Goepfert PA, Nikolich JŽ, Hsu H, Peluso MJ, Kelly JD, Okumura MJ, Flaherman VJ, Quigley JG, Krishnan JA, Scholand MB, Hess R, Metz TD, Costantine MM, Rouse DJ, Taylor BS, Goldberg MP, Marshall GD, Wood J, Warren D, Horwitz L, Foulkes AS, and McComsey GA
Subjects: Adult, Aged, Female, Humans, Male, Middle Aged, Cohort Studies, Glycated Hemoglobin analysis, Propensity Score, Biomarkers blood, COVID-19 complications, COVID-19 diagnosis, COVID-19 blood, Post-Acute COVID-19 Syndrome, SARS-CoV-2
Abstract: Background: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC)., Objective: To investigate clinical laboratory markers of SARS-CoV-2 and PASC., Design: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024)., Setting: 83 enrolling sites., Participants: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection., Measurements: Participants completed questionnaires and standard clinical laboratory tests., Results: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 10 9 cells/L [95% CI, 264.5 to 267.4 × 10 9 cells/L]) than participants without known prior infection (275.2 × 10 9 cells/L [CI, 268.5 to 282.0 × 10 9 cells/L]), as well as higher mean hemoglobin A 1c (HbA 1c ) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA 1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero., Limitation: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined., Conclusion: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0737.
Published: 2024
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37. Sex Differences in the Risk of Stroke Associated With Traditional and Non-Traditional Factors in a US Cohort of People With HIV Infection.

Author: Chow FC, Nance RM, Becker K, Ho EL, Huffer A, Kalani R, Marra CM, Zunt JR, Bamford L, Burkholder GA, Cachay E, Eron JJ, Keruly J, Kitahata MM, Napravnik S, Saag MS, Willig AL, Moore RD, Tirschwell DL, Delaney JA, and Crane HM
Subjects: Humans, Female, Male, Adult, Middle Aged, Cohort Studies, United States epidemiology, Risk Factors, Sex Factors, Sex Characteristics, HIV Infections epidemiology, HIV Infections complications, Stroke epidemiology
Abstract: Background and Objectives: Although stroke risk associated with HIV may be greater for women than men, little is known about whether the impact of different factors on cerebrovascular risk varies by sex in people with HIV (PWH) and contributes to stroke risk disparities in this population. The primary objective of this study was to examine whether sex modifies the effect of demographics, cardiometabolic factors, health-related behaviors, and HIV-specific variables on stroke risk in PWH from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort., Methods: In this observational cohort study, we analyzed data from clinical encounters for PWH followed at 5 CNICS sites from approximately 2005 to 2020. All potential stroke events were adjudicated by neurologists. Patient-reported outcomes collected at clinic visits, including substance use and depression, were also available. We used Cox proportional hazards models to determine whether sex modified the association of predictors of interest with incident stroke., Results: Among 13,573 PWH (19% female sex at birth, mean age 44 years, mean follow-up 5.6 years), female sex was associated with a higher risk of stroke only among individuals aged 50 years or younger (hazard ratio [HR] 2.01 at age 40 [1.25-3.21] vs HR 0.60 at age 60 [0.34-1.06]; p = 0.001 for the interaction). Younger female participants who developed a stroke were more likely to have treated hypertension, a higher cardiovascular risk score, and detectable HIV than younger male participants whereas these factors were comparable by sex among older participants who developed a stroke. Sex modified the effect of detectable HIV (HR 4.66 for female participants [2.48-8.74] vs HR 1.30 for male participants [0.83-2.03]; p = 0.001 for the interaction), methamphetamine use (HR 4.78 for female participants [1.47-15.56] vs HR 1.19 for male participants [0.62-2.29]; p = 0.04 for the interaction), and treated hypertension (HR 3.44 for female participants [1.74-6.81] vs HR 1.66 for male participants [1.14-2.41]; p = 0.06 for the interaction) on stroke risk., Discussion: Younger female participants with HIV were at elevated cerebrovascular risk compared with younger male participants. Several risk factors had a greater adverse effect on stroke risk in female participants than in male participants, including HIV viremia, methamphetamine use, and treated hypertension. These findings underscore the importance of a personalized approach to predict and prevent cerebrovascular risk among PWH.
Published: 2024
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38. A secukinumab dose-escalation study in patients with ankylosing spondylitis not achieving inactive disease after 16 weeks of treatment.

Author: Deodhar A, Kivitz AJ, Magrey M, Walsh JA, Mease PJ, Greenwald M, Kianifard F, Elam C, Bommidi GM, Winseck A, and Gensler LS
Abstract: Objective: To investigate the clinical response at week 52 in patients with ankylosing spondylitis (AS) who received secukinumab 300 vs 150 mg after inadequate response to 150 mg at week 16., Methods: ASLeap (NCT03350815) was a randomized, double-blind, parallel-group, multicentre, phase 4 trial. After 16 weeks of open-label secukinumab 150 mg (Treatment Period 1), patients who did not achieve inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] <1.3) at both Weeks 12 and 16 were considered to have an inadequate response and were randomized 1:1 to receive secukinumab 300 or 150 mg every 4 weeks until week 52 (Treatment Period 2). The primary efficacy variable was achievement of ASDAS <1.3 at week 52 using week 16 as baseline. Safety was evaluated by the incidence of treatment-emergent adverse events through week 52., Results: Of 322 patients treated with secukinumab in Treatment Period 1, 207 (64.3%) had inadequate response. Similar proportions of patients with inadequate response randomized to secukinumab 300 mg (n = 101) and 150 mg (n = 105) in Treatment Period 2 completed the study (83.8% and 84.3%, respectively). At week 52, 8.8% and 6.7% of patients receiving secukinumab 300 and 150 mg, respectively, achieved ASDAS <1.3. The incidence of treatment-emergent adverse events was similar in both groups through week 52. No new safety signals were observed., Conclusion: Patients with AS who did not achieve ASDAS <1.3 after receiving secukinumab 150 mg for 16 weeks experienced similar clinical response and safety through week 52 regardless of dose escalation., Trial Registration: ClinicalTrials.gov, NCT03350815., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Published: 2024
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39. The Burden of Work Productivity and Activity Impairment in Patients with Psoriasis, Psoriatic Arthritis, Ulcerative Colitis, and Crohn's Disease.

Author: Janak JC, Loughlin AM, Moore PC, Lemay CA, Mease PJ, Lebwohl M, Korzenik JR, Cross RK, and Hudesman D
Subjects: Humans, Male, Female, Adult, Middle Aged, Cross-Sectional Studies, Arthritis, Psoriatic epidemiology, Young Adult, Absenteeism, Registries, Presenteeism statistics & numerical data, Efficiency, Crohn Disease epidemiology, Crohn Disease complications, Colitis, Ulcerative epidemiology, Cost of Illness, Psoriasis epidemiology, Psoriasis complications
Abstract: Background: Comparisons among autoimmune diseases enable understanding of the burden and factors associated with work productivity loss and impairment., Aims: The objective was to compare work productivity and activity and associated factors among patients with inflammatory bowel diseases and other autoimmune conditions., Methods: This cross-sectional study included employed, adult patients (age 20-64 years) in the CorEvitas Inflammatory Bowel Disease, Psoriasis, and Psoriatic Arthritis/Spondyloarthritis Registries between 5/2017 and 6/2020. Any patient-reported impairment on four domains of the Work Productivity and Activity Index (WPAI) was collected across registries. Prevalence for each autoimmune disease was reported and stratified by disease activity using direct age-sex-standardization. Factors associated with the presence of any WPAI were identified in logistic regression models., Results: A total of 7,169 patients with psoriasis (n = 4,768, 67%), psoriatic arthritis (n = 1,208, 17%), Crohn's disease (CD, n = 621, 9%), and ulcerative colitis (UC, n = 572, 8%) met inclusion criteria. Among patients not in remission across all disease cohorts, the age-sex-standardized prevalence of any presenteeism, work productivity loss, and activity impairment ranged from 54 to 97%. Patients with CD in remission had higher standardized prevalence of presenteeism (53% [48-57%]) and work productivity loss (54% [49-59%]), compared to those from other cohorts (presenteeism [range: 33-39%] and work productivity loss [range: 37-41%]). For all WPAI domains, the strongest adjusted associations were for moderate to severe disease activity and psychosocial symptoms., Conclusions: Patients with moderate to severe disease activity reported the highest WPAI burden. However, patients in remission or mild disease activity also report some WPAI burden, emphasizing a multidisciplinary treatment approach to improve work productivity loss and impairment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Published: 2024
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40. Improvements in Patient-Reported Outcomes After Treatment With Deucravacitinib in Patients With Psoriatic Arthritis: Results From a Randomized Phase 2 Trial.

Author: Strand V, Gossec L, Coates LC, Ogdie A, Choi J, Becker B, Zhuo J, Lehman T, Nowak M, Elegbe A, Mease PJ, and Deodhar A
Subjects: Humans, Male, Female, Middle Aged, Double-Blind Method, Adult, Treatment Outcome, Protein Kinase Inhibitors therapeutic use, Protein Kinase Inhibitors adverse effects, Arthritis, Psoriatic drug therapy, Arthritis, Psoriatic diagnosis, Patient Reported Outcome Measures
Abstract: Objective: Deucravacitinib, a tyrosine kinase 2 inhibitor, was assessed in a phase 2 trial in patients with active psoriatic arthritis (PsA). Here, we report effects of deucravacitinib from the patient perspective., Methods: This phase 2, double-blind trial (NCT03881059) randomized patients with active PsA 1:1:1 to deucravacitinib 6 mg once daily (QD), 12 mg QD, or placebo, for 16 weeks. Key secondary end points were changes from baseline (CFBs) at week 16 in Health Assessment Questionnaire-Disability Index (HAQ-DI) and 36-item Short-Form Health Survey (SF-36) physical component summary (PCS) scores. Additional patient-reported outcomes (PROs) assessed disease impact, including fatigue, pain, and mental health. The mean CFBs in PROs and percentages of patients reporting improvements with minimum clinically important differences (MCIDs) or scores of greater than normal values were also assessed., Results: This study comprised 203 patients (51.2% female; mean ± SD age, 49.8 ± 13.5 years). At week 16, the adjusted mean difference (95% confidence interval) versus placebo in HAQ-DI and SF-36 PCS CFB was significant for each deucravacitinib group (HAQ-DI 6 mg, -0.26 [-0.42 to -0.10], P = 0.0020; HAQ-DI 12 mg, -0.28 [-0.45 to -0.12], P = 0.0008; SF-36 PCS 6 mg, 3.3 [0.9 to 5.7], P = 0.0062; SF-36 PCS 12 mg, 3.5 [1.1 to 5.9], P = 0.0042). MCID at week 16 were reported for all PROs with either dose of deucravacitinib. Improvements of MCID or to normative values were reported by more patients receiving deucravacitinib than placebo., Conclusion: Deucravacitinib groups demonstrate significant and clinically meaningful improvements in PROs versus placebo in patients with active PsA, which warrants further study., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)
Published: 2024
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41. Durable control of psoriatic arthritis with guselkumab across domains and patient characteristics: post hoc analysis of a phase 3 study.

Author: Ritchlin CT, Mease PJ, Boehncke WH, Tesser J, Chakravarty SD, Rampakakis E, Shawi M, Schiopu E, Merola JF, McInnes IB, and Deodhar A
Subjects: Humans, Male, Female, Middle Aged, Adult, Treatment Outcome, Double-Blind Method, Antirheumatic Agents therapeutic use, Cross-Over Studies, Arthritis, Psoriatic drug therapy, Antibodies, Monoclonal, Humanized therapeutic use, Patient Reported Outcome Measures, Severity of Illness Index
Abstract: Objectives: Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics., Method: This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W); guselkumab at Weeks 0 and 4, then Q8W; or placebo with crossover to guselkumab Q4W at Week 24. Achievement of American College of Rheumatology 50/70% improvement (ACR50/70), Investigator's Global Assessment (IGA) 0, dactylitis/enthesitis resolution, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response (≥ 4-point improvement), HAQ-Disability Index (HAQ-DI) response (≥ 0.35-point improvement), PsA Disease Activity Score (PASDAS) low disease activity (LDA), and minimal disease activity (MDA) was assessed at Weeks 24, 52, and 100 in subgroups defined by sex and baseline medication use, body mass index, PsA duration, swollen/tender joints, CRP, and psoriasis severity/extent. Patients with missing categorical response data were considered nonresponders., Results: 442/493 (90%) guselkumab-randomized patients completed treatment through Week 100. Significant multi-domain efficacy of guselkumab versus placebo was shown across adequately sized patient subgroups. A pattern of continuous improvement was observed across key PsA domains and PROs within patient subgroups: 65%-85% of guselkumab-randomized patients had enthesitis/dactylitis resolution, 50%-70% achieved complete skin clearance, 60%-80% reported meaningful improvements in function/fatigue, 40%-65% achieved PASDAS LDA, and 35%-50% achieved MDA at Week 100., Conclusion: Patients with active PsA receiving guselkumab demonstrated durable achievement of stringent endpoints associated with disease control across key PsA domains and PROs, regardless of baseline characteristics. Key Points • Among biologic-naïve patients with highly active psoriatic arthritis (PsA), efficacy of guselkumab across stringent disease endpoints and patient-reported outcomes (PROs) at Week 24 was consistent regardless of baseline demographics and disease characteristics. • Within guselkumab-randomized PsA patient subgroups, major improvements in joint disease activity, complete skin clearance, dactylitis/enthesitis resolution, clinically meaningful improvements in PROs, and achievement of low overall disease activity were maintained through Week 100. • Durable stringent endpoint achievement indicating disease control was observed with guselkumab, regardless of baseline patient or disease characteristics., (© 2024. The Author(s).)
Published: 2024
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42. Correction: Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial.

Author: de Vlam K, Maksymowych WP, Gallo G, Rahman P, Mease P, Krishnan V, McVeigh CJ, Lisse J, Zhu D, Bolce RJ, and Conaghan PG
Published: 2024
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43. Clinicopathologic Characterization of 2 Individuals With TBK1 Variants-1 Novel Splice Variant, 2 Proteinopathies: A Case Series.

Author: Domoto-Reilly K, Distad BJ, Miller DE, Lin YH, Ivanick D, Warren AS, Jayadev S, and Latimer CS
Abstract: Objectives: Here, we report detailed clinicopathologic evaluation of 2 individuals with pathogenic variants in TBK1 , including one novel likely pathogenic splice variant. We describe the striking diversity of clinical phenotypes among family members and also the brain and spinal cord neuropathology associated with these 2 distinct TBK1 variants., Methods: Two individuals with pathogenic variants in TBK1 and their families were clinically characterized, and the probands subsequently underwent extensive postmortem neuropathologic examination of their brains and spinal cords., Results: Multiple affected individuals within a single family were found to carry a previously unreported c.358+3A>G variant, predicted to alter splicing. Detailed histopathologic evaluation of our 2 TBK1 variant carriers demonstrated distinct TDP-43 pathologic subtypes, but shared argyrophilic grain disease (AGD) tau pathology., Discussion: Although all pathogenic TBK1 variants are associated with TDP-43 pathology, the clinical and histologic features can be highly variable. Within one family, we describe distinct neurologic presentations which we propose are all caused by a novel c.358+3A>G variant. AGD is typically associated with older age, but it has been described as a copathologic finding in other TBK1 variant carriers and may be a common feature in FTLD-TDP due to TBK1 ., Competing Interests: K. Domoto-Reilly reports research funding from NIH U19AG063911; B.J. Distad reports no disclosures relevant to the manuscript; D.E. Miller reports participation on a scientific advisory board at Oxford Nanopore Technologies (ONT), engagement in a research agreement with ONT, and has received travel compensation from ONT; Y.-H. Lin reports no disclosures relevant to the manuscript; D. Ivanick reports no disclosures relevant to the manuscript; A.S. Warren reports no disclosures relevant to the manuscript; S. Jayadev reports no disclosures relevant to the manuscript; C. Latimer reports no disclosures relevant to the manuscript. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Published: 2024
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44. Comparative efficacy and safety of bimekizumab in psoriatic arthritis: a systematic literature review and network meta-analysis.

Author: Mease PJ, Gladman DD, Merola JF, Nash P, Grieve S, Laliman-Khara V, Willems D, Taieb V, Prickett AR, and Coates LC
Subjects: Humans, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized adverse effects, Network Meta-Analysis, Randomized Controlled Trials as Topic, Treatment Outcome, Antirheumatic Agents therapeutic use, Antirheumatic Agents adverse effects, Arthritis, Psoriatic drug therapy
Abstract: Objectives: To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of IL-17F in addition to IL-17A, vs other biologic and targeted synthetic DMARDs (b/tsDMARDs) for PsA using network meta-analysis (NMA)., Methods: A systematic literature review (most recent update conducted on 1 January 2023) identified randomized controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12-24 for b/tsDMARD-naïve and TNF inhibitor (TNFi)-experienced patients. Safety at Weeks 12-24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank., Results: The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-experienced patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th and 3rd for ACR response ACR20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index 90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-experienced patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events., Conclusion: Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Published: 2024
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45. Navigating the complexity of pain in psoriatic arthritis and axial spondyloarthritis.

Author: Mease PJ
Subjects: Humans, Pain Management methods, Neuralgia etiology, Neuralgia physiopathology, Arthritis, Psoriatic complications, Arthritis, Psoriatic physiopathology, Arthritis, Psoriatic psychology, Axial Spondyloarthritis diagnosis, Axial Spondyloarthritis complications, Axial Spondyloarthritis etiology, Axial Spondyloarthritis physiopathology
Abstract: Purpose of Review: Pain is the most common and often most troublesome feature of chronic autoimmune diseases such as psoriatic arthritis (PsA) and axial spondyloarthritis (AxSpA). A predominant concept is that the main source of pain is from disease-induced tissue inflammation and structural damage, activating peripheral nerve fibers which relay to the central nervous system. This mechanism is nociceptive pain and the presumption has been that controlling inflammation will be sufficient to reduce this form of pain. However, despite control of inflammation, patients may still have significant residual pain., Recent Findings: We are learning that there are additional pain mechanisms, neuropathic and nociplastic, that are often operative in patients with rheumatologic conditions, that can significantly influence pain experience, quantitation of disease activity, and may benefit from therapeutic approaches distinct from immunotherapy. Neuropathic pain arises from diseased or damaged nerve tissue and nociplastic pain reflects sensitization of the central nervous system due to multiple genetic, neurobiologic, neural network dysregulation, and psychosocial factors. Pain arising from these mechanisms influence assessment of disease activity and thus needs to be factored into decision-making about immunotherapy efficacy., Summary: This review addresses the importance of accurately assessing the complex mechanisms of pain experience in patients with PsA and AxSpA to more appropriately manage immunomodulatory, neuromodulatory, and nonpharmacologic therapies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
Published: 2024
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46. The Postoperative Airway Compromise Score-First Steps to Developing a Postoperative Tool for the Assessment of Upper Airway-Related Complications Following Anterior Cervical Spine Surgery.

Author: von Glinski A, Pierre CA, Elia C, Ishak B, Godolias P, Blecher R, Detorri JR, Norvell DC, Jouppi L, Gerstmeyer J, Deem SA, Golden JB, Schildhauer TA, Oskouian RJ, and Chapman JR
Subjects: Humans, Male, Female, Middle Aged, Aged, Risk Factors, Adult, Delphi Technique, Airway Obstruction etiology, Cervical Vertebrae surgery, Postoperative Complications etiology, Postoperative Complications epidemiology, Spinal Fusion adverse effects, Diskectomy adverse effects
Abstract: Background: Acute upper airway compromise is a rare but catastrophic complication after anterior cervical discectomy and fusion. This study aims to develop a score to identify patients at risk of acute postoperative airway compromise (PAC)., Methods: Potential risk factors for acute PAC were selected by a modified Delphi process. Ten patients with acute PAC were identified of 1466 patients who underwent elective anterior cervical discectomy and fusion between July 2014 and May 2019. A comparison group was created by a randomized selection process (non-PAC group). Factors associated with PAC and a P value of < 0.10 were entered into a logistic regression model and coefficients contributed to each risk factor's overall score. Calibration of the model was evaluated using the Hosmer-Lemeshow goodness-of-fit test. Quantitative discrimination was calculated, and the final model was internally validated with bootstrap sampling., Results: We identified 18 potential risk factors from our Delphi process, of which 6 factors demonstrated a significant association with airway compromise: age >65 years, current smoking status, American Society of Anesthesiologists class >2, history of a bleeding disorder, surgery of upper subaxial cervical spine (above C4), and duration of surgery >179 minutes. The final prediction model included 5 predictors with very strong performance characteristics. These 5 factors formed the PAC score, with a range from 0 to 100. A score of 20 yielded the greatest balance of sensitivity (80%) and specificity (88%)., Conclusions: The acute PAC score demonstrates strong performance characteristics. The PAC score might help identify patients at risk of upper airway compromise caused by surgical site abnormalities., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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47. Deciphering difficult-to-treat psoriatic arthritis (D2T-PsA): a GRAPPA perspective from an international survey of healthcare professionals.

Author: Ribeiro AL, Singla S, Chandran V, Chronis N, Liao W, Lindsay C, Soriano ER, Mease PJ, and Proft F
Abstract: Objectives: This study contributes to the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)'s effort to define 'difficult-to-treat' PsA (D2T-PsA), leveraging insights of healthcare professionals who are GRAPPA members. The primary objective is to inform GRAPPA's D2T PsA project, ensuring the consensus definition reflects clinical experience and expertise., Methods: An online survey was conducted among GRAPPA's healthcare professionals managing PsA patients. The survey covered demographic details, structured questions, and open-ended queries to gather comprehensive insights into the experts' viewpoints., Results: About 223 physicians completed the survey, comprising 179 (80.2%) rheumatologists and 40 (17.9%) dermatologists. The majority, 184 (82.5%), favoured establishing distinct definitions for D2T-PsA and complex-to-manage PsA (C2M-PsA). Furthermore, 202 (90.5%) supported a definition that includes objective inflammation signs (clinical, laboratory, imaging, among others). However, opinions varied on the criteria for prior treatment failures, with most (93, 41.7%) favouring a definition that includes at least one conventional synthetic disease-modifying anti-rheumatic drug and two or more biological- or targeted-synthetic-DMARDs with different mechanisms of action., Conclusion: The survey reveals a majority opinion among GRAPPA experts favouring the differentiation between D2T-PsA and C2M-PsA, and the inclusion of objective inflammatory markers in these definitions. However, there is less than 50% agreement on the specific treatment failure criteria, particularly regarding the number of therapies needed to classify PsA as D2T. These findings suggest a need for continued discussion to reach a more unified approach in defining D2T-PsA, reflecting the complexity of the condition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)
Published: 2024
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48. SARS-CoV-2 Antiviral Prescribing Gaps Among Nonhospitalized High-Risk Adults.

Author: Levy ME, Burrows E, Chilunda V, Pawloski PA, Heaton PR, Grzymski J, Goldman JD, McEwen LM, Wyman D, Dei Rossi A, Dai H, Isaksson M, Washington NL, Basler T, Tsan K, Nguyen J, Ramirez J, Sandoval E, Lee W, Lu J, and Luo S
Subjects: Humans, Male, Middle Aged, Female, Adult, Aged, Risk Factors, Ritonavir therapeutic use, COVID-19 epidemiology, Adenosine Monophosphate analogs & derivatives, Adenosine Monophosphate therapeutic use, Alanine therapeutic use, Alanine analogs & derivatives, Practice Patterns, Physicians' statistics & numerical data, Cytidine analogs & derivatives, Hydroxylamines, Antiviral Agents therapeutic use, SARS-CoV-2, COVID-19 Drug Treatment
Abstract: Within a multistate clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among nonhospitalized patients with SARS-CoV-2 with risk factors for severe COVID-19. Among 3247 adults, only 31.9% were prescribed an antiviral agent (87.6% nirmatrelvir/ritonavir, 11.9% molnupiravir, 0.5% remdesivir), highlighting the need to identify and address treatment barriers., Competing Interests: Potential conflicts of interest. M. E. L., V. C., L. M. M., D. W., A. D. R., H. D., M. I., N. L. W., T. B., K. T., J. N., J. R., E. S., W. L., J. L., and S. L. are employees of Helix, Inc. M. E. L., M. I., and S. L. report contracted research from Pfizer. M. E. L., M. I., W. L., and S. L. report contracted research from the Centers for Disease Control and Prevention (CDC). M. I., M. E. L., J. L., D. W., and S. L. report support for attending meetings and/or travel from Helix. M. I., M. E. L., W. L., A. D. R., J. L., D. W., and N. L. W. report stock or stock options from Helix. M. E. L. reports contracted research and travel support from Novavax. E. B. is an employee of Janssen Pharmaceuticals and a prior employee of Helix, Inc. P. R. H. reports contracted research from Seegene USA and Helix, Inc. J. G. is employed by the University of Nevada, Reno, and Renown Health, and reports a professional relationship with the Desert Research Institute and research funding from Gilead Sciences and the National Institute of Environmental Health Sciences (NIEHS); reports consulting fees from Renown Health; and US Patent Application 63/467,250 “Dynamic risk management for breast cancer based on multi-factor genetic testing” with Dr. Alexandre Bolze. J. D. G. reports contracted research from Helix, Gilead, Eli Lilly, and Regeneron; grants from Merck (BARDA) and Gilead; speaking honoraria and personal fees from Gilead Sciences, Inc, and Eli Lilly & Co; and collaborative services agreements with Adaptive Biotechnologies, Monogram Biosciences, and LabCorp; and serving as a speaker or advisory board member for Gilead and Eli Lilly. J. G., M. I., N. L. W., and S. L. report patents pending or issued to Helix, Inc (M. I. and S. L.: US-11776694-B2 and US-20230178236-A1). P. A. P. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Published: 2024
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49. Exploring the Effects of Ixekizumab on Pain in Patients with Ankylosing Spondylitis Based on Objective Measures of Inflammation: Post Hoc Analysis from a Large Randomized Clinical Trial.

Author: de Vlam K, Maksymowych WP, Gallo G, Rahman P, Mease P, Krishnan V, McVeigh CJ, Lisse J, Zhu D, Bolce RJ, and Conaghan PG
Abstract: Introduction: The objective of this analysis is to evaluate the improvement in spinal pain with ixekizumab, placebo, and adalimumab based on objective measures of inflammation response in patients with ankylosing spondylitis (AS)., Methods: The COAST-V 52-week, double-blind, placebo-controlled, randomized phase III trial examined the efficacy of ixekizumab in patients with active AS; adalimumab was used as an active reference arm. Treatment effects on reduction in pain were assessed by objective measures of controlled and persisting inflammation (defined by magnetic resonance imaging [MRI], C-reactive protein [CRP], or MRI + CRP status). Pathway analysis was used to analyze treatment effect that was not attributable to reduction in inflammation biomarkers., Results: In patients with AS, when inflammation was controlled as assessed by MRI, patients treated with ixekizumab experienced a reduction in spinal pain at night (SP-N, numeric rating scale, ixekizumab mean = - 3.9, p < 0.001, adalimumab mean = - 2.6, p < 0.05) compared to placebo (mean = - 1.6) at week 16. When inflammation was controlled as assessed by MRI + CRP, ixekizumab and adalimumab had numerically greater reductions at week 16 in SP-N versus placebo. All ixekizumab groups had further improvements at week 52. When inflammation was persisting as assessed by MRI + CRP, ixekizumab-treated patients had significant reduction in SP-N (mean = - 3.7, p < 0.001) versus placebo (mean = - 1.7), improvement with adalimumab did not reach significance (mean = - 2.6, p = 0.06). In the pathway analysis at week 16, ixekizumab had a greater effect on pain outcomes compared to adalimumab., Conclusion: This post hoc analysis is supportive of the hypothesis that ixekizumab reduces pain in AS by additional mechanisms other than the reduction of measurable inflammation., Trial Registration Number: NCT02696785., (© 2024. The Author(s).)
Published: 2024
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50. Comparative Effectiveness of Bimekizumab and Secukinumab in Patients with Psoriatic Arthritis at 52 Weeks Using a Matching-Adjusted Indirect Comparison.

Author: Mease PJ, Warren RB, Nash P, Grouin JM, Lyris N, Willems D, Taieb V, Eells J, and McInnes IB
Abstract: Introduction: Matching-adjusted indirect comparisons (MAICs) were used to compare the efficacy of bimekizumab and secukinumab 150 mg and 300 mg at 52 weeks for the treatment of psoriatic arthritis (PsA) in patients who were biologic disease-modifying anti-rheumatic drug-naïve (bDMARD-naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR)., Methods: Relevant trials were systematically identified. Individual patient data from bimekizumab randomized controlled trials, BE OPTIMAL (N = 431) and BE COMPLETE (N = 267), were matched to aggregate data from bDMARD-naïve and TNFi-IR patient subgroups from FUTURE 2 using secukinumab 150 mg and 300 mg doses (bDMARD-naïve: N = 63/37; TNFi-IR: N = 67/33). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of patients in the secukinumab trials. Unanchored comparisons of recalculated bimekizumab and secukinumab 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed., Results: In patients who were bDMARD-naïve, bimekizumab had a greater likelihood of ACR70 response than secukinumab 150 mg (odds ratio [95% confidence interval] 2.39 [1.26, 4.53]; p = 0.008) and secukinumab 300 mg (2.03 [1.11, 3.72]; p = 0.021) at 52 weeks. In patients who were TNFi-IR, bimekizumab had a greater likelihood of response compared to secukinumab 150 mg for ACR20 (3.50 [1.64-7.49]; p = 0.001), ACR50 (3.32 [1.41, 7.80]; p = 0.006), ACR70 (2.95 [1.08, 8.07]; p = 0.035) and MDA (3.52 [1.38, 8.99]; p = 0.009), and a greater likelihood of response compared to secukinumab 300 mg for ACR50 (2.44 [1.06, 5.65]; p = 0.037) and MDA (2.92 [1.20, 7.09]; p = 0.018) at 52 weeks., Conclusion: In this MAIC analysis, the efficacy of bimekizumab, as demonstrated by the likelihood of ACR20/50/70 and MDA response at 52 weeks, was greater or comparable to secukinumab 150 mg and 300 mg for patients with PsA who were bDMARD-naïve and TNFi-IR., Trial Registration Numbers: NCT03895203, NCT03896581, NCT04009499, NCT01752634, NCT01989468, NCT02294227, NCT02404350., (© 2024. The Author(s).)
Published: 2024
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