385 results on '"Clifton O. Bingham"'
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2. The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study
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Paul Emery, Yoshiya Tanaka, Vivian P. Bykerk, Clifton O. Bingham, Thomas W. J. Huizinga, Gustavo Citera, Kuan-Hsiang Gary Huang, Chun Wu, Sean E. Connolly, Yedid Elbez, Robert Wong, Karissa Lozenski, and Roy Fleischmann
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Rheumatoid arthritis ,Anti-citrullinated protein antibody ,Sustained remission ,Abatacept ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background AVERT-2 (a phase IIIb, two-stage study) evaluated abatacept + methotrexate versus methotrexate alone, in methotrexate-naive, anti-citrullinated protein antibody-positive patients with early (≤ 6 months), active RA. This subanalysis investigated whether individual patients who achieved the week 24 Simplified Disease Activity Index (SDAI) remission primary endpoint could sustain remission to 1 year and then maintain it following changes in therapy. Methods During the 56-week induction period (IP), patients were randomized to weekly subcutaneous abatacept 125 mg + methotrexate or abatacept placebo + methotrexate. Patients completing the IP who achieved SDAI remission (≤ 3.3) at weeks 40 and 52 entered a 48-week de-escalation (DE) period. Patients treated with abatacept + methotrexate were re-randomized to continue weekly abatacept + methotrexate, or de-escalate and then withdraw abatacept (after 24 weeks), or receive abatacept monotherapy. Proportions of patients achieving sustained SDAI and Boolean remission, and Disease Activity Score in 28 joints using C-reactive protein (DAS28 [CRP])
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- 2023
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3. Three doses of COVID-19 mRNA vaccine induce class-switched antibody responses in inflammatory arthritis patients on immunomodulatory therapies
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Jenny M. Lee, Alexis Figueroa, Jaiprasath Sachithanandham, Maggie Li, Caoilfhionn M. Connolly, Janna R. Shapiro, Yiqun Chen, Michelle Jones, Venkata Gayatri Dhara, Marilyn Towns, John S. Lee, Stephanie R. Peralta, Aaron M. Milstone, Michael Betenbaugh, Amanda K. Debes, Joel Blankson, Ioannis Sitaras, Steve Yoon, Elizabeth A. Thompson, Clifton O. Bingham, Sabra L. Klein, Andrew Pekosz, and Justin R. Bailey
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SARS-CoV-2 ,mRNA vaccines ,immunosuppression ,inflammatory arthritis ,variants of concern ,serological response ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Patients with inflammatory arthritis (IA) are at increased risk of severe COVID-19 due to medication-induced immunosuppression that impairs host defenses. The aim of this study was to assess antibody and B cell responses to COVID-19 mRNA vaccination in IA patients receiving immunomodulatory therapies. Adults with IA were enrolled through the Johns Hopkins Arthritis Center and compared with healthy controls (HC). Paired plasma and peripheral blood mononuclear cell (PBMC) samples were collected prior to and 30 days or 6 months following the first two doses of mRNA vaccines (D2; HC=77 and IA=31 patients), or 30 days following a third dose of mRNA vaccines (D3; HC=11 and IA=96 patients). Neutralizing antibody titers, total binding antibody titers, and B cell responses to vaccine and Omicron variants were analyzed. Anti-Spike (S) IgG and S-specific B cells developed appropriately in most IA patients following D3, with reduced responses to Omicron variants, and negligible effects of medication type or drug withholding. Neutralizing antibody responses were lower compared to healthy controls after both D2 and D3, with a small number of individuals demonstrating persistently undetectable neutralizing antibody levels. Most IA patients respond as well to mRNA COVID-19 vaccines as immunocompetent individuals by the third dose, with no evidence of improved responses following medication withholding. These data suggest that IA-associated immune impairment may not hinder immunity to COVID-19 mRNA vaccines in most individuals.
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- 2023
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4. Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis
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Paul Emery, Yoshiya Tanaka, Vivian P. Bykerk, Thomas W. J. Huizinga, Gustavo Citera, Clifton O. Bingham, Subhashis Banerjee, Benjamin P. Soule, Marleen Nys, Sean E. Connolly, Karissa L. Lozenski, Joe Zhuo, Robert Wong, Kuan-Hsiang Gary Huang, and Roy Fleischmann
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Abatacept ,Anti-citrullinated protein autoantibodies (ACPAs) ,Clinical trial ,Disease-modifying antirheumatic drugs (DMARDs) ,Rheumatoid arthritis ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Introduction One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA. Methods The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate. Primary endpoint: SDAI remission (≤ 3.3) at week 24. Pre-planned exploratory endpoint: maintenance of remission in patients with sustained remission (weeks 40 and 52) who, from week 56 for 48 weeks (DE period), (1) continued combination abatacept + methotrexate, (2) tapered abatacept to every other week (EOW) + methotrexate for 24 weeks with subsequent abatacept withdrawal (abatacept placebo + methotrexate), or (3) withdrew methotrexate (abatacept monotherapy). Results Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm achieved SDAI remission at week 24 (p = 0.2359). There were numerical differences favoring combination therapy in clinical assessments, patient-reported outcomes (PROs) and week 52 radiographic non-progression. After week 56, 147 patients in sustained remission with abatacept + methotrexate were randomized (combination, n = 50; DE/withdrawal, n = 50; abatacept monotherapy, n = 47) and entered DE. At DE week 48, SDAI remission (74%) and PRO improvements were mostly maintained with continued combination therapy; lower remission rates were observed with abatacept placebo + methotrexate (48.0%) and with abatacept monotherapy (57.4%). Before withdrawal, de-escalating to abatacept EOW + methotrexate preserved remission. Conclusions The stringent primary endpoint was not met. However, in patients achieving sustained SDAI remission, numerically more maintained remission with continued abatacept + methotrexate versus abatacept monotherapy or withdrawal. Trial Registration ClinicalTrials.gov identifier, NCT02504268. Video abstract (MP4 62241 KB)
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- 2023
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5. Response to Treatment with Intravenous Golimumab or Infliximab in Rheumatoid Arthritis Patients: PROMIS Results from the Real-World Observational Phase 4 AWARE Study
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Clifton O. Bingham, Shawn Black, Natalie J. Shiff, Stephen Xu, Wayne Langholff, and Jeffrey R. Curtis
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Rheumatoid arthritis ,PROMIS ,Patient-reported outcomes ,Intravenous golimumab ,Infliximab ,Depression ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Introduction To assess changes in the Patient-Reported Outcomes Measurement Information System (PROMIS®) outcomes related to social, mental, and physical well-being after approximately 1 year of intravenous (IV) golimumab or infliximab treatment in patients with rheumatoid arthritis (RA) using real-world evidence from AWARE. Methods AWARE was a prospective, noninterventional, multicenter, observational, U.S.-based phase 4 study of 1270 RA patients who initiated treatment with IV golimumab or infliximab. PROMIS-29 and PROMIS short form (SF) Fatigue 7a and Pain Interference 6b questionnaires were administered at baseline and infusions 2, 5, and 8 (approximately weeks 4, 28, and 52 for IV golimumab and weeks 2, 22, and 46 for infliximab). Mean changes from baseline in all PROMIS-29 domains and respective SFs and response rates for achieving ≥ 3, ≥ 5, or ≥ 10-point improvements were determined. Results Among all patients, baseline mean ± SD PROMIS T-scores were consistent between treatment groups and indicated worse physical function (38.2 ± 6.8 IV golimumab, 38.0 ± 6.9 infliximab), more pain interference (63.0 ± 7.6 IV golimumab, 63.9 ± 7.8 infliximab), and greater fatigue (58.4 ± 9.9 IV golimumab, 59.4 ± 10.0 infliximab) in these patients vs the general U.S. population (T-score = 50). Through the 8th infusion of either treatment, IV golimumab- and infliximab-treated patients achieved meaningful improvements (≥ 3-point improvement in T-scores) in all PROMIS-29 domains and respective SFs, and the proportions of patients with ≥ 3, ≥ 5, or ≥ 10-point improvements in T-scores increased from infusion 2 through infusion 8. Conclusions RA patients treated with IV golimumab or infliximab achieved comparable improvements across social, mental, and physical well-being PROMIS measures. Additionally, PROMIS detected meaningful clinical changes in patient-reported outcomes in both treatment groups. ClinicalTrials.gov registration number NCT02728934.
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- 2023
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6. Citrullination modulates antigen processing and presentation by revealing cryptic epitopes in rheumatoid arthritis
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Ashley M. Curran, Alexander A. Girgis, Yura Jang, Jonathan D. Crawford, Mekha A. Thomas, Ryan Kawalerski, Jeff Coller, Clifton O. Bingham, Chan Hyun Na, and Erika Darrah
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Science - Abstract
Antibodies directed against citrullinated proteins are commonly found in patients with rheumatoid arthritis. Here, the authors show that citrullination alters the peptide repertoire presented to T cells by altering protease cleavage and inducing protein destabilization, thereby exposing cryptic epitopes.
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- 2023
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7. Machine Learning Applied to Patient‐Reported Outcomes to Classify Physician‐Derived Measures of Rheumatoid Arthritis Disease Activity
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Jeffrey R. Curtis, Yujie Su, Shawn Black, Stephen Xu, Wayne Langholff, Clifton O. Bingham, Shelly Kafka, and Fenglong Xie
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Objective Patient‐reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician‐derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated. Methods Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross‐validated error, comparing different ML approaches using both training and test data. Results A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient‐Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%. Conclusion ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real‐world evidence generation in the common circumstance when physician‐derived disease activity data are not available yet PRO measures are.
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- 2022
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8. Association between low hemoglobin, clinical measures, and patient-reported outcomes in patients with rheumatoid arthritis: results from post hoc analyses of three phase III trials of sarilumab
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Andrea Rubbert-Roth, Daniel E. Furst, Stefano Fiore, Amy Praestgaard, Vivian Bykerk, Clifton O. Bingham, Christina Charles-Schoeman, and Gerd Burmester
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Rheumatoid arthritis ,Sarilumab ,Patient-reported outcomes ,Anemia ,Hemoglobin ,Radiographic outcomes ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Anemia is common in patients with rheumatoid arthritis (RA). Higher hemoglobin (Hb) levels may be associated with better clinical outcomes and patient-reported outcomes (PROs). To assess this hypothesis, we conducted two post hoc analyses in three sarilumab phase III studies: TARGET, MOBILITY, and MONARCH. Methods Pooled data from combination therapy from placebo-controlled MOBILITY (sarilumab + methotrexate) and TARGET (sarilumab + conventional synthetic disease-modifying antirheumatic drugs [csDMARDs]) and monotherapy data from active-controlled MONARCH (sarilumab vs. adalimumab) studies were included. Associations between Hb levels and clinical measures and PROs were assessed over 24 weeks. The mean changes from baseline in clinical outcomes and PROs (to week 24) and radiographic outcomes (to week 52) were evaluated between low and normal Hb levels (based on the World Health Organization [WHO] criteria). Results From TARGET, MOBILITY, and MONARCH, 546, 1197, and 369 patients, respectively, were stratified according to Hb levels (low vs. normal). Over 24 weeks, higher Hb levels were found to be consistently associated with better clinical outcomes and PROs in combination therapy and monotherapy groups and were more pronounced among the patients treated with sarilumab than those treated with placebo and adalimumab. The mean change from baseline to week 24 in clinical efficacy measures and PROs was similar in patients with low vs. normal Hb at baseline. Differences between sarilumab and/or adalimumab, for all outcomes, were larger for low Hb subgroups. In MOBILITY, by week 52, the inhibition of progression of structural damage (assessed via Modified Total Sharp Score [mTSS]) was 84% (sarilumab 200 mg) and 68% (sarilumab 150 mg) vs. placebo in patients with low Hb and 97% (sarilumab 200 mg) and 68% (sarilumab 150 mg) vs. placebo in patients with normal Hb. Similar results were observed for other radiographic outcomes. Conclusions In these post hoc analyses, a consistent relationship was observed between higher Hb levels and better clinical outcomes and PROs in patients with RA. Irrespective of the baseline Hb levels, sarilumab treatment was associated with improvements in clinical measures and PROs over 24 weeks (improvements were more pronounced than those with adalimumab treatment) and mitigation of joint damage progression over 52 weeks. Trial registration ClinTrials.gov NCT01061736, NCT01709578, and NCT02332590
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- 2022
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9. The impact of tofacitinib on fatigue, sleep, and health-related quality of life in patients with rheumatoid arthritis: a post hoc analysis of data from Phase 3 trials
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Susan J. Bartlett, Clifton O. Bingham, Ronald van Vollenhoven, Christopher Murray, David Gruben, David A. Gold, and David Cella
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Fatigue ,Health-related quality of life ,Patient-reported outcomes ,Rheumatoid arthritis ,Sleep ,Tofacitinib ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Fatigue, a common symptom of rheumatoid arthritis (RA), is detrimental to health-related quality of life (HRQoL). We evaluated the impact of tofacitinib on fatigue, sleep, and HRQoL and explored associations between fatigue, related patient-reported outcomes (PROs), and disease activity in RA patients. Methods This post hoc analysis pooled data from three Phase 3 studies of tofacitinib (ORAL Scan; ORAL Standard; ORAL Sync) in RA patients. Patients received tofacitinib 5 or 10 mg twice daily, placebo, or adalimumab (active control; ORAL Standard only, not powered for superiority) with conventional synthetic disease-modifying antirheumatic drugs. Assessed through Month (M)12 were changes from baseline in disease activity, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Medical Outcomes Study Sleep scale (MOS-SS), and Short Form-36 Health Survey (SF-36) composite/domain scores, and proportions of patients reporting improvements from baseline in FACIT-F total and SF-36 domain scores ≥ minimum clinically important differences (MCIDs) or ≥ population normative values. Pearson correlations examined associations among PROs at M6. Treatment comparisons were exploratory, with p < 0.05 considered nominally significant. Results Generally, active treatment led to significant improvements from baseline in FACIT-F total, and MOS-SS and SF-36 composite/domain scores vs placebo, observed by M1 and maintained through M6 (last placebo-controlled time point). Through M6, more patients achieved improvements from baseline ≥ MCID and achieved scores ≥ population normative values in FACIT-F total and SF-36 domain scores with tofacitinib vs placebo. Through M12, some nominally significant improvements with tofacitinib vs adalimumab were observed. With active treatment at M6, FACIT-F scores were moderately (0.40–0.59) to highly (≥ 0.60) correlated with SF-36 composite/domain scores (particularly vitality), moderately correlated with most MOS-SS domain scores, and highly correlated with MOS-SS Sleep Problems Index I scores. Disease activity correlations were moderate with FACIT-F scores and low (0.20–0.39) to moderate with SF-36 general health domain/composite scores. Conclusion Tofacitinib and adalimumab generally conferred significant, clinically meaningful improvements in fatigue, sleep, and HRQoL (including vitality) vs placebo through M6, with improvements maintained to M12. M6 correlations between FACIT-F, PROs of sleep, HRQoL, and disease activity underscore the interrelatedness of multiple PROs and disease activity in RA. Trial registration ClinicalTrials.gov NCT00847613 (registered: February 19, 2009); NCT00853385 (registered: March 2, 2009); NCT00856544 (registered: March 5, 2009).
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- 2022
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10. The impact of filgotinib on patient-reported outcomes and health-related quality of life for patients with active rheumatoid arthritis: a post hoc analysis of Phase 3 studies
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Clifton O. Bingham, David Walker, Peter Nash, Susan J. Lee, Lei Ye, Hao Hu, Javaria Mona Khalid, and Bernard Combe
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Filgotinib ,Patient-reported outcomes ,HAQ-DI ,SF-36 ,FACIT-Fatigue ,WPAI ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background The effects of filgotinib on patient-reported outcomes (PROs) from 3 trials in patients with active rheumatoid arthritis were investigated. Methods Methotrexate (MTX)-naïve patients received filgotinib 200 or 100 mg plus MTX (FIL200+MTX, FIL100+MTX), filgotinib 200 mg monotherapy (FIL200), or MTX monotherapy through 52 weeks (NCT02886728). Patients with inadequate response (IR) to MTX (MTX-IR) received FIL200+MTX, FIL100+MTX, adalimumab 40 mg +MTX (ADA+MTX), or placebo (PBO)+MTX (rerandomized to FIL200+MTX or FIL100+MTX at week 24) through 52 weeks (NCT02889796). Patients with IR to biologic disease-modifying antirheumatic drugs (bDMARD-IR) received FIL200 or FIL100 or PBO with background stable conventional synthetic (cs) DMARDs for up to 24 weeks (NCT02873936). PROs included Health Assessment Questionnaire-Disability Index (HAQ-DI), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) physical/mental component summary (PCS/MCS), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), Work Productivity and Activity Impairment Questionnaire-Rheumatoid Arthritis (WPAI-RA), and Patient Global Assessment of Disease Activity (PtGA). Data are reported as least-squares mean changes from baseline with standard error to the timepoint representing each study’s primary endpoint. All statistical comparisons are of filgotinib groups vs their respective control groups. Results At week 24, among MTX-naïve patients, change from baseline (standard deviation) in HAQ-DI was − 1.00 (0.03; P < 0.001) with FIL200+MTX, − 0.94 (0.04; P < 0.01) with FIL100+MTX, and − 0.91 (0.04; P < 0.05) with FIL200 alone compared with − 0.81 (0.03) with MTX alone. At week 12, among MTX-IR patients, change from baseline in HAQ-DI was − 0.69 (0.04; P < 0.001 vs PBO+MTX, P < 0.05 vs ADA) with FIL200+MTX, − 0.57 (0.04; P < 0.001 vs placebo) with FIL100+MTX, and − 0.60 (0.04) with ADA vs − 0.40 (0.04) with PBO+MTX. At week 12, among bDMARD-IR patients, change from baseline in HAQ-DI was − 0.50 (0.06; P < 0.001) with FIL200+csDMARD and − 0.46 (0.05; P < 0.001) with FIL100+csDMARD vs − 0.19 (0.06) with placebo+csDMARD. Changes in SF-36 PCS and MCS, FACIT-Fatigue, WPAI, and PtGA tended to favor filgotinib over PBO, MTX, and ADA. Greater proportions of patients experienced clinically meaningful differences with either dosage of FIL in combination with csDMARDs (including MTX) and with FIL200 monotherapy vs comparators. Conclusions Filgotinib provided improvements in PROs across patient populations. These findings suggest filgotinib can be an effective treatment option for patients with insufficient response to MTX or bDMARDs and patients who are MTX-naïve. Trial registration ClinicalTrials.gov , FINCH 1, NCT02889796 , first posted September 7, 2016; FINCH 2, NCT02873936 , first posted August 22, 2016, retrospectively registered; FINCH 3, NCT02886728 , first posted September 1, 2016, retrospectively registered.
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- 2022
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11. Learning Needs of Patients with Cancer and a Pre-Existing Autoimmune Disease Who Are Candidates to Receive Immune Checkpoint Inhibitors
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Maria A. Lopez-Olivo, Johncy J. Kachira, Maryam Buni, Sang Taek Kim, Huifang Lu, Jean H. Tayar, Gabrielle F. Duhon, Juan I. Ruiz, Clifton O. Bingham, Cassandra Calabrese, Robert J. Volk, and Maria E. Suarez-Almazor
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qualitative interviews ,patient education ,immunotherapy ,autoimmune diseases ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Patients with pre-existing autoimmune disorders and cancer considering immune checkpoint inhibitors (ICIs) need to receive balanced information about the benefits and risk of developing immune-related adverse events (irAEs) and flare-ups of their autoimmune disease. To assess the learning needs of patients with cancer and pre-existing autoimmune disease regarding ICI treatment, we interviewed 29 patients with autoimmune disease and cancer from a comprehensive cancer center, of whom 20 had received ICI and 9 were candidates to receive ICI at a US Cancer Center. In-depth semi-structured interviews were conducted from August 2021 and January 2022. Interviewee’s opinions and preferences about content and information delivery methods were collected. We recorded and transcribed interviews and analyzed them using thematic analysis. Half of the participants were female, and their median (SD) age was 62.9 (±10.9) years. The identified health information needs included the following: (1) information on irAEs and autoimmune disease flare-ups; (2) benefits of ICI; (3) ICI mechanism in the context of autoimmune disease; (4) management of flare-ups; (5) reasons for stopping or modifying cancer or autoimmune disease treatment; (6) likelihood of autoimmune disease progression or organ damage; and (7) lifestyle changes that could help avoid irAEs. Patients who had received ICI and those who had not yet received treatment reported similar needs, although patients who had received ICI had more questions about cancer treatment modifications. Patients also expressed the need to better understand when to contact their provider and how to share information with multiple providers. Most patients wanted to receive information in visual formats for review at home and at their own pace. Patients expressed interest in having educational tools to facilitate shared decision-making with their physicians, and they identified several areas of health information concerning therapy with ICI. They also highlighted the importance of communication among their various providers.
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- 2023
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12. Physician Views on the Provision of Information on Immune Checkpoint Inhibitor Therapy to Patients with Cancer and Pre-Existing Autoimmune Disease: A Qualitative Study
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Maria A. Lopez-Olivo, Gabrielle F. Duhon, Juan I. Ruiz, Mehmet Altan, Hussein Tawbi, Adi Diab, Clifton O. Bingham, Cassandra Calabrese, Natalia I. Heredia, Robert J. Volk, and Maria E. Suarez-Almazor
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qualitative interviews ,patient education ,immunotherapy ,autoimmune diseases ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Immune checkpoint inhibitors (ICIs) have improved cancer outcomes but can cause severe immune-related adverse events (irAEs) and flares of autoimmune conditions in cancer patients with pre-existing autoimmune disease. The objective of this study was to identify the information physicians perceived as most useful for these patients when discussing treatment initiation with ICIs. Twenty physicians at a cancer institution with experience in the treatment of irAEs were interviewed. Qualitative thematic analysis was performed to organize and interpret data. The physicians were 11 medical oncologists and 9 non-oncology specialists. The following themes were identified: (1) current methods used by physicians to provide information to patients and delivery options; (2) factors to make decisions about whether or not to start ICIs in patients who have cancer and pre-existing autoimmune conditions; (3) learning points for patients to understand; (4) preferences for the delivery of ICI information; and (5) barriers to the implementation of ICI information in clinics. Regarding points to discuss with patients, physicians agreed that the benefits of ICIs, the probability of irAEs, and risks of underlying autoimmune condition flares with the use of ICIs were most important. Non-oncologists were additionally concerned about how ICIs affect the autoimmune disease (e.g., impact on disease activity, need for changes in medications for the autoimmune disease, and monitoring of autoimmune conditions).
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- 2023
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13. Postapproval Comparative Safety Study of Tofacitinib and Biological Disease‐Modifying Antirheumatic Drugs: 5‐Year Results from a United States–Based Rheumatoid Arthritis Registry
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Joel M. Kremer, Clifton O. Bingham III, Laura C. Cappelli, Jeffrey D. Greenberg, Ann M. Madsen, Jamie Geier, Jose L. Rivas, Alina M. Onofrei, Christine J. Barr, Dimitrios A. Pappas, Heather J. Litman, Kimberly J. Dandreo, Andrea B. Shapiro, Carol A. Connell, and Arthur Kavanaugh
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5‐year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease‐modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry. Methods IRs (number of first events/100 patient‐years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow‐up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable‐adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long‐term (malignancy and death) events. VTEs were assessed descriptively. Results For MACE, SIEs, and HZ, 1999 (3152.1 patient‐years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient‐years) and 6354 (16 670.8 patient‐years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS‐trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43‐3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13‐0.54) and 0.33 (0.24‐0.45) for tofacitinib and bDMARDs, respectively. Conclusion In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators.
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- 2021
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14. Immune checkpoint inhibitor-induced inflammatory arthritis: a qualitative study identifying unmet patient needs and care gaps
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Laura C. Cappelli, Suzanne M. Grieb, Ami A. Shah, Clifton O. Bingham, and Ana-Maria Orbai
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Immunotherapy ,Cancer ,Inflammatory arthritis ,Quality of life ,Social support ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Patients treated for cancer with immune checkpoint inhibitors (ICI) may develop autoimmune adverse events, including ICI-induced inflammatory arthritis (IA). ICI-induced IA treatment requires balancing immune activation to fight cancer and immune modulation to control autoimmunity. Our objective was to learn how patients experience ICI-induced IA and potentially conflicting treatment decisions. Methods Semi-structured interviews were conducted with participants with rheumatologist-diagnosed ICI-induced IA recruited from a longitudinal cohort. The interview guide probed the experience of diagnosis and treatment, symptoms and impact of ICI-induced IA, coping mechanisms, and treatment decision-making. Two researchers used an iterative coding process to identify themes through inductive thematic analysis and consensus. An overarching conceptual framework was derived from the qualitative analysis to identify care gaps perceived by patients, and inform future research. Results Fourteen patients with ICI-induced IA participated in semi-structured interviews. Five overarching themes were identified: an awareness gap leading to delay in diagnosis of IA, descriptors of ICI-induced IA and relationship to other adverse events, emotional and quality-of-life impact of IA, fear and decision-making, and contextual factors including social support. Conclusions As reported by patients, ICI-induced IA had a significant functional and emotional impact, even as compared to cancer and other ICI-induced side effects. Increasing awareness and integrated care of ICI-induced IA, and increasing social support are key targets for improving patient care. Additionally, more data on cancer outcomes in patients requiring immunomodulation for ICI-induced IA would help address fear and uncertainty for patients, and better support them through therapeutic decisions.
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- 2020
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15. Patients with checkpoint inhibitor‐induced inflammatory arthritis do not become seropositive for anti‐cyclic citrullinated peptide when followed over time
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Laura C. Cappelli, Erika Darrah, Ami A. Shah, and Clifton O. Bingham
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Diseases of the musculoskeletal system ,RC925-935 - Published
- 2022
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16. Sonographic Findings in Inflammatory Arthritis Secondary to Immune Checkpoint Inhibition: A Case Series
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Jemima Albayda, Eric Dein, Ami A. Shah, Clifton O. Bingham III, and Laura Cappelli
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Diseases of the musculoskeletal system ,RC925-935 - Abstract
Objective Immune checkpoint inhibitors (ICI) are transforming the field of oncology, leading to tumor regression in multiple advanced cancers. With this case series, we review the ultrasound imaging findings in a series of patients with ICI‐induced inflammatory arthritis (IA), a novel rheumatic disease that is caused by cancer immunotherapy. Methods We identified patients with rheumatologist‐diagnosed, ICI‐induced IA who had musculoskeletal ultrasound performed for clinical care. A retrospective chart review was done to obtain demographics, oncologic history, clinical presentation, imaging, and synovial fluid results. Ultrasound images were reviewed and scored for synovial and tendon pathology, presence of Doppler, and bony erosion. Results Nine patients were included in this study with a total of 18 joint regions assessed. The knees were the most commonly imaged joint followed by the hands, wrists, feet, and ankles. Synovitis was seen in 12 of the 18 joints with active Doppler in 50% of the cases. Tendon involvement was also frequently seen (13 of 18 joints) with tenosynovitis, tendinitis, and enthesophytes. Erosions were less frequent and seen in only three cases but were also an early finding. Conclusion Patients with ICI‐induced IA had a wide range of pathology affecting the synovium, tendons, and bones on musculoskeletal ultrasound. Further systematic study with imaging is needed for this group of diseases.
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- 2019
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17. Evaluation of pneumococcal and tetanus vaccine responses in patients with rheumatoid arthritis receiving baricitinib: results from a long-term extension trial substudy
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Kevin L. Winthrop, Clifton O. Bingham, Wendy J. Komocsar, John Bradley, Maher Issa, Rena Klar, and Cynthia E. Kartman
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Rheumatoid arthritis ,Vaccination ,DMARDs (biologics) ,Janus kinase inhibitors ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Clinical guidelines recommend pneumococcal and tetanus vaccinations in patients with rheumatoid arthritis (RA). Baricitinib is an oral, selective Janus kinase (JAK) 1/JAK 2 inhibitor and is approved for the treatment of moderately to severely active RA in adults in over 50 countries including European countries, the USA, and Japan. This substudy evaluated pneumococcal conjugate and tetanus toxoid vaccine (TTV) responses in patients with RA receiving baricitinib. These vaccines elucidate predominantly T cell-dependent humoral antibody response. Methods Eligible RA patients receiving baricitinib 2 mg or 4 mg with or without concomitant methotrexate (MTX) were enrolled in a phase 3 long-term extension trial (RA-BEYOND; ClinicalTrials.gov, NCT01885078) in USA/Puerto Rico. Patients were vaccinated with 13-serotype pneumococcal conjugate vaccine (PCV-13) and TTV. Primary endpoints were the proportion of patients achieving a satisfactory humoral response for PCV-13 (≥ 2-fold increase in anti-pneumococcal antibody concentrations in ≥ 6 serotypes) and TTV (≥ 4-fold increase in anti-tetanus concentrations) at 5 weeks post-vaccination. Secondary endpoints included humoral responses at 12 weeks and functional responses of serotypes 4, 6B, 14, and 23F (twofold and fourfold increases in opsonic indexes at 5 and 12 weeks). Results Of 106 patients with a mean duration of RA of approximately 12 years, 80% were female, 30% were taking corticosteroids, and 89% (N = 94) were taking baricitinib plus MTX; most patients (97% PCV-13/96% TTV) completed the evaluations. Overall, 68% (95% CI 58.4, 76.2) of patients achieved a satisfactory response to PCV-13, 43% (34.0, 52.8) achieved a ≥ 4-fold increase in anti-tetanus concentrations, and 74% (64.2, 81.1) achieved a ≥ 2-fold increase. PCV-13 response was similar for patients taking corticosteroids (71%; 53.4, 83.9) vs those not (67%; 55.2, 76.5). The percentage of sera with a ≥ 2-fold increase in post-vaccination opsonic indexes at week 5 ranged from 47% (serotype 14) to 76% (serotype 6B). Through 12 weeks post-vaccination, seven patients (6.6%) reported injection-site events. There were no deaths during the substudy, and three patients experienced a serious adverse event. Conclusions Approximately two thirds of patients on long-term baricitinib achieved satisfactory humoral and functional responses to PCV-13 vaccination, while TTV responses were less robust. PCV-13 response was not diminished in those taking concomitant corticosteroids. Trial registration ClinicalTrials.gov, NCT01885078. Registered on 24 June 2013.
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- 2019
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18. Use of daily electronic patient-reported outcome (PRO) diaries in randomized controlled trials for rheumatoid arthritis: rationale and implementation
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Clifton O. Bingham, Carol L. Gaich, Amy M. DeLozier, Kathryn D. Engstrom, April N. Naegeli, Stephanie de Bono, Pixy Banerjee, and Peter C. Taylor
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Daily electronic diary ,ePRO ,Patient-reported outcome ,Rheumatoid arthritis ,Medicine (General) ,R5-920 - Abstract
Abstract Background Rheumatoid arthritis (RA) is associated with significantly diminished health-related quality of life. Patient-reported outcomes (PROs) are considered important in RA; however, some symptoms such as morning joint stiffness (MJS) and fatigue that are considered important by patients are not captured by the American College of Rheumatology “core set” measures for RA trials. The US Food and Drug Administration has endorsed electronic capture of clinical trial data including PROs, and electronic PRO (ePRO) systems may lead to more accurate and complete data capture, improved compliance, and patient acceptance compared with paper-based methods. Our objective was to assess the implementation of ePRO measures of Duration and Severity of MJS, Severity of Worst Tiredness, and Severity of Worst Joint Pain in baricitinib RA-BEAM and RA-BUILD phase 3 randomized clinical trials (RCTs). Methods A daily electronic diary (handheld device; Invivodata®, Inc.) was utilized to capture PRO data in the RCTs. Three “reporting window” options were incorporated to accommodate differences in patients’ routine daily schedules, and alarms were programmed for each reporting window. Duration of MJS was recorded in “hours and minutes,” and Severity of MJS, Worst Tiredness, and Worst Joint Pain were captured on a 0 to 10 rating scale, with a higher score indicating more severe symptoms. The patients and site staff were trained to use the daily electronic diary. Results Patients with moderately to severely active RA used the daily electronic diary in the RA-BEAM study (N = 1305) and RA-BUILD study (N = 684). The average compliance, calculated as total days completed by patients compared with total days expected to complete the diary, through Week 12 was high (RA-BEAM 94% patients; RA-BUILD 93% patients), potentially attributable to appropriate training, clarity of instructions, simple user interface, and electronic device design. Identified process challenges included non-timely issuance of the device, low battery, inadequate training of patients before data collection, inappropriate diary set-up, and first response entry 1 day after the baseline visit. Conclusions High compliance rates support the use of the daily electronic PRO diary in large RCTs. Despite the anticipated issues, the daily electronic diary is expected to reduce recall bias and improve the quality of PRO data collection. Trial registration RA-BEAM (NCT01710358) and RA-BUILD (NCT01721057).
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- 2019
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19. PROMIS Fatigue short forms are reliable and valid in adults with rheumatoid arthritis
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Clifton O. Bingham III, Anna Kristina Gutierrez, Alessandra Butanis, Vivian P. Bykerk, Jeffrey R. Curtis, Amye Leong, Anne Lyddiatt, W. Benjamin Nowell, Ana Maria Orbai, and Susan J. Bartlett
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Patient reported outcomes ,Fatigue ,Rheumatoid arthritis ,Validation ,PROMIS ,Public aspects of medicine ,RA1-1270 - Abstract
Abstract Background Fatigue is prevalent and impactful in rheumatoid arthritis (RA). There is no standardized measure for its assessment nor data concerning the performance of PROMIS-Fatigue short forms (SFs) in people with RA. We evaluated the construct validity of 4-, 7-, and 8-item PROMIS-Fatigue SFs in RA patients across the range of disease activity. Methods Adult RA patients were recruited from an online patient community and an observational cohort from three academic medical centers. Measures included PROMIS-Fatigue SFs, other PROMIS measures, and other patient reported outcomes including RAND-36 Vitality, Fatigue NRS, and patient global assessment of disease activity. Other measures from the observational cohort included 28-joint swollen and tender joints, physician global assessment, and the composite RA clinical disease activity index (CDAI). Results Two-hundred online participants and 348 participants from the observational cohort were included. PROMIS Fatigue SF scores spanned the measurement continuum and correlated highly with each other (r’s ≥ 0.91) and other fatigue measures (r’s ≥ 0.85). PROMIS-Fatigue SF scores were highly and inversely associated with Physical Function and Participation (r’s − 0.77 to − 0.78), and moderately-highly and positively correlated with pain, sleep disturbance, anxiety, and depression (r’s 0.60 to 0.75). PROMIS-Fatigue SF scores showed dose-response relationships across fatigue severity descriptors and CDAI categories. Conclusions These results provide robust evidence supporting the construct validity of the 4, 7, and 8-item PROMIS-Fatigue SFs. They capture fatigue across the spectrum of RA disease activity in diverse groups of individuals and should be considered for use as patient-centered assessments of disease control and treatment efficacy.
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- 2019
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20. 292 Fibromyalgianess and Glucocorticoid Persistence Among Patients with Rheumatoid Arthritis
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Beth Wallace, Meriah N. Moore, Andrew C. Heisler, Lutfiyya N. Muhammad, Jing Song, Daniel J. Clauw, Clifton O. Bingham, Marcy B. Bolster, Wendy Marder, Tuhina Neogi, Alyssa Wohlfahrt, Dorothy D. Dunlop, and Yvonne C. Lee
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Medicine - Abstract
OBJECTIVES/GOALS: Over 30% of patients with rheumatoid arthritis (RA) exhibit fibromyalgianess, a symptom cluster associated with increased pain sensitivity. Up to half of RA patients use oral glucocorticoids (GCs) long-term despite their known, dose-dependent toxicity. We examined the association between fibromyalgianess and oral GC persistence in RA patients. METHODS/STUDY POPULATION: We used data from the Central Pain in Rheumatoid Arthritis (CPIRA) cohort to follow participants with active RA on oral prednisone who initiated a new disease-modifying anti-rheumatic drug. We measured fibromyalgianess using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key fibromyalgia features often superimposed upon RA. We stratified fibromyalgianess severity as follows: FSQ10 high/very high. We defined GC persistence as GC use at 3 month followup visit. We assessed the association between baseline fibromyalgianess (exposure) and GC persistence at followup (outcome) using multiple logistic regression, adjusted for demographics, RA duration, serostatus, and inflammatory activity measured by swollen joint count and C reactive protein. RESULTS/ANTICIPATED RESULTS: Of 97 participants on prednisone at baseline, 65% were taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent GC use, compared to 84% with high or very high fibromyalgianess. After adjustment as outlined above, participants with high/very high baseline fibromyalgianess remained more likely to be on prednisone at follow-up, relative to those with low fibromyalgianess (OR 4.99 [95% CI 1.20 – 20.73]). DISCUSSION/SIGNIFICANCE: In this cohort of patients with active RA, high fibromyalgianess is associated with persistent GC use, independent of inflammatory activity. This finding suggests non-inflammatory pain related to fibromyalgianess may be misclassified as inflammatory pain related to RA disease activity.
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- 2022
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21. Immune-related adverse events with immune checkpoint inhibitors affecting the skeleton: a seminal case series
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Kendall F. Moseley, Jarushka Naidoo, Clifton O. Bingham, Michael A. Carducci, Patrick M. Forde, Geoffrey T. Gibney, Evan J. Lipson, Ami A. Shah, William H. Sharfman, and Laura C. Cappelli
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Immunotherapy ,Immune-related adverse events ,Bone resorption ,Fracture ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The use of immune checkpoint inhibitors is increasing in cancer therapy today. It is critical that treatment teams become familiar with the organ systems potentially impacted by immune-related adverse events associated with these drugs. Here, we report adverse skeletal effects of immunotherapy, a phenomenon not previously described. Case presentations In this retrospective case series, clinical, laboratory and imaging data were obtained in patients referred to endocrinology or rheumatology with new fractures (n = 3) or resorptive bone lesions (n = 3) that developed while on agents targeting PD-1, CTLA-4 or both. The average age of patients was 59.3 (SD 8.6), and five were male. Cancer types included melanoma, renal cell carcinoma and non-small cell lung cancer. All fracture patients had vertebral compression, and two of the three had multiple fracture sites involved. Sites of resorptive lesions included the shoulder, hand and clavicle. Biochemically, elevated or high-normal markers of bone resorption were seen in five of the six patients. Erythrocyte sedimentation rate was elevated in three of the four patients where checked. Conclusions This case series represents the first description of potential skeletal adverse effects related to immune checkpoint inhibitors. These findings are important for providers caring for patients who experience musculoskeletal symptoms and may merit additional evaluation.
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- 2018
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22. Evaluation of Musculoskeletal and Pulmonary Bacterial Infections With [I]FIAU PET/CT
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Steve Y. Cho MD, Steven P. Rowe MD, PhD, Sanjay K. Jain MD, Lew C. Schon MD, Rex C. Yung MD, Tariq A. Nayfeh MD, PhD, Clifton O. Bingham MD, Catherine A. Foss PhD, Sridhar Nimmagadda PhD, and Martin G. Pomper MD, PhD
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Biology (General) ,QH301-705.5 ,Medical technology ,R855-855.5 - Abstract
Purpose: Imaging is limited in the evaluation of bacterial infection. Direct imaging of in situ bacteria holds promise for noninvasive diagnosis. We investigated the ability of a bacterial thymidine kinase inhibitor ([ 124 I]FIAU) to image pulmonary and musculoskeletal infections. Methods: Thirty-three patients were prospectively accrued: 16 with suspected musculoskeletal infection, 14 with suspected pulmonary infection, and 3 with known rheumatoid arthritis without infection. Thirty-one patients were imaged with [ 124 I]FIAU PET/CT and 28 with [ 18 F]FDG PET/CT. Patient histories were reviewed by an experienced clinician with subspecialty training in infectious diseases and were determined to be positive, equivocal, or negative for infection. Results: Sensitivity, specificity, positive-predictive value, negative-predictive value, and accuracy of [ 124 I]FIAU PET/CT for diagnosing infection were estimated as 7.7% to 25.0%, 0.0%, 50%, 0.0%, and 20.0% to 71.4% for musculoskeletal infections and incalculable-100.0%, 51.7% to 72.7%, 0.0% to 50.0%, 100.0%, and 57.1% to 78.6% for pulmonary infections, respectively. The parameters for [ 18 F]FDG PET/CT were 75.0% to 92.3%, 0.0%, 23.1% to 92.3%, 0.0%, and 21.4% to 85.7%, respectively, for musculoskeletal infections and incalculable to 100.0%, 0.0%, 0.0% to 18.2%, incalculable, and 0.0% to 18.2% for pulmonary infections, respectively. Conclusions: The high number of patients with equivocal clinical findings prevented definitive conclusions from being made regarding the diagnostic efficacy of [ 124 I]FIAU. Future studies using microbiology to rigorously define infection in patients and PET radiotracers optimized for image quality are needed.
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- 2020
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23. Smoking is not linked to the development of anti-peptidylarginine deiminase 4 autoantibodies in rheumatoid arthritis
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Laura C. Cappelli, Maximilian F. Konig, Allan C. Gelber, Clifton O. Bingham, and Erika Darrah
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Rheumatoid arthritis ,Smoking ,PAD enzymes ,Shared epitope ,CCP ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background Defining environmental factors responsible for development of autoimmunity in rheumatoid arthritis (RA) is critical for understanding mechanisms of disease initiation and propagation. Notably, a history of cigarette smoking has been implicated in the genesis of RA and is associated with worse disease outcomes. Antibodies to peptidylarginine deiminase 4 (PAD4) are also associated with more severe RA. A subset of patients who have PAD4 autoantibodies that cross-react with PAD3 (anti-PAD3/4) are at the highest risk for interstitial lung disease, and this risk is augmented by a history of cigarette smoking. It is unclear, however, if smoking is etiologically linked to the development of anti-PAD4 antibodies. Methods Patients were included in this study if they had physician-diagnosed RA as well as DNA, serum, and a date-matched clinical assessment (n = 274). Anti-PAD4 and anti-CCP antibodies were measured by immunoprecipitation and ELISA, respectively; shared epitope (SE) status was determined by HLA-DRβ1 genotyping. Logistic regression analysis was used to evaluate associations of smoking with PAD4 antibodies, with adjustment for relevant demographic and clinical features. Stratified analyses by disease duration and shared epitope status were also performed. Results Anti-PAD4 antibodies were present in 25% of RA patients, with 50% of these individuals having anti-PAD3/4 cross-reactive antibodies. Anti-PAD4 antibodies were significantly associated with a longer disease duration, SE alleles, and anti-CCP antibodies. Importantly, there were no significant differences in smoking history between anti-PAD4 positive and negative groups in univariate analyses, stratified analyses, or multivariable models. However, an inverse relationship between smoking and anti-PAD4 antibodies was suggested by a lower prevalence of current smokers among patients with anti-PAD3/4 antibodies compared to antibody negative individuals (p = 0.04). Further, the lowest levels of anti-PAD4 antibodies were observed in current smokers (p = 0.14), and a significant association of SE and anti-PAD4 antibodies was only present among never smokers (p = 0.01). Conclusions Smoking history was not associated with anti-PAD4 antibodies in patients with RA. The finding that anti-PAD4 antibodies were not associated with smoking suggests that other environmental factors may contribute to the development of autoimmunity to PAD4 in these patients.
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- 2018
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24. Soluble Markers of Antibody Secreting Cell Function as Predictors of Infection Risk in Rheumatoid Arthritis
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Maria J. Gutierrez, Stephen V. Desiderio, Nae-Yuh Wang, Erika Darrah, Laura Cappelli, Gustavo Nino, Michelle Jones, and Clifton O. Bingham
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Background. Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with immune dysregulation and increased risk of infections. The presence of autoantibodies and immunoglobulin abnormalities indicates B-cell and antibody-secreting cell (ASC) dysfunction. We hypothesize that soluble factors associated with B-cell and ASC activity are decreased in RA patients and that this is linked to higher susceptibility to infections. Methods. Using the Johns Hopkins Arthritis Cohort and Biorepository, we contrasted serum protein levels of soluble factors involved in B-cell activation (CD40, CD40L) and B-cell/ASC homing (CXCL10, CXCL11, and CXCL13) or survival (BAFF, APRIL, TACI, and BCMA) in 10 healthy subjects and 23 adult RA patients (aged 24-65 years). We subdivided RA patients into those with (n=17) and those without infections (n=6) within a 2-year period. In order to reduce the effect of RA treatment, we only included patients receiving methotrexate monotherapy or no RA treatments at baseline. Soluble serum protein levels of B-cell/ASC factors were quantified by multiplex immunoassays. Results. We identified that (1) serum levels of soluble BCMA, APRIL, CD40, and CD40L were significantly decreased in RA patients relative to healthy individuals; (2) serum soluble BCMA, predominantly released by ASC, correlated with serum concentrations of class-switched immunoglobulins, IgG and IgA; and (3) RA patients with a history of infections had significantly lower soluble BCMA levels compared with healthy donors and with RA patients without infections. Conclusions. Our study using soluble factors linked to B-cell/ASC activation and survival suggests that there is a paucity of ASC in a subset of RA patients and that this may be linked to altered antibody production and increased risk of infections. Further delineating the link between ASC and infection susceptibility in RA may optimize disease management and provide novel insights into disease pathogenesis that are susceptible to intervention.
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- 2019
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25. Autoantibodies to Peptidylarginine Deiminase 2 Are Associated With Less Severe Disease in Rheumatoid Arthritis
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Erika Darrah, Jon T. Giles, Ryan L. Davis, Pooja Naik, Hong Wang, Maximilian F. Konig, Laura C. Cappelli, Clifton O. Bingham, Sonye K. Danoff, and Felipe Andrade
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rheumatoid arthritis ,peptidylarginine deiminase ,autoantibodies ,autoimmunity ,disease activity ,interstitial lung disease ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Objective: Peptidylarginine deiminases (PAD) 2 and 4 are key enzymes in rheumatoid arthritis (RA) pathogenesis due to their ability to generate the protein targets of anti-citrullinated protein antibodies (ACPA). Anti-PAD4 antibodies that cross-react with PAD3 (anti-PAD3/4) have been identified and are associated with severe joint and lung disease. Here, we examined whether anti-PAD2 antibodies were present in patients with RA and defined their clinical significance.Patients and Methods: A PAD2 ELISA was established to screen for anti-PAD2 IgG in sera from RA patients from a prospective observational cohort study (n = 184) and healthy controls (n = 100). RA patient characteristics were compared according to anti-PAD2 antibody status. Multivariable models were constructed to explore the independent associations of anti-PAD2 antibodies with clinical variables.Results: Anti-PAD2 antibodies were found in 18.5% of RA patients and 3% of healthy controls (p < 0.001). Among RA patients, anti-PAD2 antibodies were not associated with traditional genetic or serologic RA risk factors, including HLA-DRβ1 shared epitope alleles, ACPA, rheumatoid factor (RF), or anti-PAD3/4 antibodies. In addition, antibodies to PAD2 were associated with fewer swollen joints, a lower prevalence of interstitial lung disease, and less progression of joint damage. In subset analyses in which patients were stratified by the baseline presence of ACPA/RF or anti-PAD3/4 antibodies, anti-PAD2 antibodies provided additional value in identifying patients with the least progressive joint disease.Conclusions: Anti-PAD2 antibodies represent a novel serologic marker in RA that identifies a genetically and clinically unique subset of patients with less severe joint and lung disease.
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- 2018
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26. Spontaneous Secretion of the Citrullination Enzyme PAD2 and Cell Surface Exposure of PAD4 by Neutrophils
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Yebin Zhou, Bo Chen, Nanette Mittereder, Raghothama Chaerkady, Martin Strain, Ling-Ling An, Saifur Rahman, Wenting Ma, Choon Pei Low, Denice Chan, Frances Neal, Clifton O. Bingham, Kevon Sampson, Erika Darrah, Richard M. Siegel, Sarfaraz Hasni, Felipe Andrade, Katherine A. Vousden, Tomas Mustelin, and Gary P. Sims
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neutrophil ,citrullination ,PAD2 ,PAD4 ,rheumatoid arthritis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Autoantibodies directed against citrullinated epitopes of proteins are highly diagnostic of rheumatoid arthritis (RA), and elevated levels of protein citrullination can be found in the joints of patients with RA. Calcium-dependent peptidyl-arginine deiminases (PAD) are the enzymes responsible for citrullination. PAD2 and PAD4 are enriched in neutrophils and likely drive citrullination under inflammatory conditions. PADs may be released during NETosis or cell death, but the mechanisms responsible for PAD activity under physiological conditions have not been fully elucidated. To understand how PADs citrullinate extracellular proteins, we investigated the cellular localization and activity of PAD2 and PAD4, and we report that viable neutrophils from healthy donors have active PAD4 exposed on their surface and spontaneously secrete PAD2. Neutrophil activation by some stimulatory agents increased the levels of immunoreactive PAD4 on the cell surface, and some stimuli reduced PAD2 secretion. Our data indicate that live neutrophils have the inherent capacity to express active extracellular PADs. These novel pathways are distinguished from intracellular PAD activation during NETosis and calcium influx-mediated hypercitrullination. Our study implies that extracellular PADs may have a physiological role under non-pathogenic conditions as well as a pathological role in RA.
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- 2017
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27. Correction to: Use of daily electronic patient-reported outcome (PRO) diaries in randomized controlled trials for rheumatoid arthritis: rationale and implementation
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Clifton O. Bingham, Carol L. Gaich, Amy M. DeLozier, Kathryn D. Engstrom, April N. Naegeli, Stephanie de Bono, Pixy Banerjee, and Peter C. Taylor
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Medicine (General) ,R5-920 - Abstract
After publication of the original article [1], the authors have notified us of an error in language used in the text:
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- 2019
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28. Pain Sensitization as a Potential Mediator of the Relationship Between Sleep Disturbance and Subsequent Pain in Rheumatoid Arthritis
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Jing Song, Lutfiyya N. Muhammad, Tuhina Neogi, Dorothy D. Dunlop, Alyssa Wohlfahrt, Marcy B. Bolster, Clifton O. Bingham, Daniel J. Clauw, Wendy Marder, and Yvonne C. Lee
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Rheumatology - Abstract
Many patients with rheumatoid arthritis (RA) experience sleep disturbances, commonly attributed to joint pain. Sleep disturbances could also influence pain. One mechanism may be through dysregulated pain processing, manifested by enhanced pain sensitivity. The present study was undertaken to examine the role of pain sensitization, measured by quantitative sensory testing (QST), as a mediator in the pathway of sleep disturbance leading to subsequent pain.We used longitudinal data from 221 patients with active RA who were followed for 12 weeks after initiating a disease-modifying antirheumatic drug. Baseline QST included pressure pain thresholds at articular (wrists, knees) and nonarticular (trapezius, thumbnails) sites, temporal summation (TS) at the wrist and forearm, and conditioned pain modulation (CPM). Baseline sleep disturbance and subsequent pain intensity were assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS). We evaluated correlations between sleep disturbance, QSTs, and subsequent pain intensity. Mediation analyses separately assessed each QST as a mediator, adjusting for baseline confounding factors.Sleep disturbance was correlated with all QST measures except wrist TS and CPM. Sleep disturbance significantly predicted subsequent pain (coefficient for a meaningful increase of 5 units in sleep disturbance = 0.32 (95% confidence interval 0.11, 0.50) in multiple regression. QST mediated 10-19% of this effect.Pain sensitization may be one mechanism through which sleep disturbance contributes to pain. The small magnitude of association indicates that unmeasured pathways may contribute to this relationship. Intervention studies are needed to establish causality and determine whether improving sleep can improve pain in patients with RA.
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- 2022
29. Machine Learning Applied to <scp>Patient‐Reported</scp> Outcomes to Classify <scp>Physician‐Derived</scp> Measures of Rheumatoid Arthritis Disease Activity
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Jeffrey R. Curtis, Yujie Su, Shawn Black, Stephen Xu, Wayne Langholff, Clifton O. Bingham, Shelly Kafka, and Fenglong Xie
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Rheumatology - Abstract
Patient-reported outcome (PRO) data have assumed increasing importance in the care of patients with rheumatoid arthritis (RA), yet physician-derived disease activity measures, such as Clinical Disease Activity Index (CDAI), remain the most accepted metrics to assess disease activity. The possibility that newer longitudinal PRO data might be used as a proxy for the CDAI has not been evaluated.Using data from a large pragmatic trial, we evaluated patients with RA initiating golimumab intravenous or infliximab. The classification target was low disease activity (LDA) (CDAI ≤10) at the first visit between months 3 and 12. Data were randomly partitioned into training (80%) and test (20%) data sets. Multiple machine learning (ML) methods (eg, random forests, gradient boosting, support vector machines) were used to classify CDAI disease activity category, conduct feature selection, and assess feature importance. Model performance evaluated cross-validated error, comparing different ML approaches using both training and test data.A total of 494 patients were analyzed, and 36.4% achieved LDA. The most important classification features included several Patient-Reported Outcomes Measurement Information System measures (social participation, pain interference, pain intensity, and physical function), patient global, and baseline CDAI. Among all ML methods, random forests performed best. Overall model accuracy and positive predictive values for all ML methods were approximately 80%.ML methods coupled with longitudinal PRO data appear useful and can achieve reasonable accuracy in classifying LDA among patients starting a new biologic. This approach has promise for real-world evidence generation in the common circumstance when physician-derived disease activity data are not available yet PRO measures are.
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- 2022
30. Treatment goals for rheumatoid arthritis: patient engagement and goal collection
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Zachary Predmore, Emily K Chen, Thomas W Concannon, Suzanne Schrandt, Susan J Bartlett, Clifton O Bingham, Richard Z Xie, Richard H Chapman, and Lori Frank
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Health Policy - Abstract
Aim: We developed the Patient-Engaged Health Technology Assessment strategy for survey-based goal collection from patients to yield patient-important outcomes suitable for use in multi-criteria decision analysis. Methods: Rheumatoid arthritis patients were recruited from online patient networks for proof-of-concept testing of goal collection and prioritization using a survey. A Project Steering Committee and Expert Panel rated the feasibility of scaling to larger samples. Results: Survey respondents (n = 47) completed the goal collection exercise. Finding effective treatments was rated by respondents as the most important goal, and reducing stiffness was rated as the least important. Feedback from our steering committee and expert panel support the approach's feasibility for goal identification and ranking. Conclusion: Goals relevant for treatment evaluation can be identified and rated for importance by patients to permit wide input from patients with lived experience of disease.
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- 2023
31. Comparative effectiveness of TNF inhibitor vs IL-6 receptor inhibitor as monotherapy or combination therapy with methotrexate in biologic-experienced patients with rheumatoid arthritis: An analysis from the CorEvitas RA Registry
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Anthony Sebba, Clifton O. Bingham, Vivian P. Bykerk, Stefano Fiore, Kerri Ford, Jud C. Janak, Dimitrios A. Pappas, Taylor Blachley, Swapna S. Dave, Joel M. Kremer, Miao Yu, and Ernest Choy
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Rheumatology ,General Medicine - Abstract
Objective Randomized controlled trials (RCTs) in biologic-naïve rheumatoid arthritis (RA) patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 (IL-6) receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy. This observational study aimed to compare the effectiveness of TNFi vs IL-6Ri as mono- or combination therapy in biologic/targeted synthetic (b/ts) -experienced RA patients with moderate/high disease activity. Methods Eligible b/ts-experienced patients from the CorEvitas RA registry were categorized as TNFi and IL-6Ri initiators, with subgroups initiating as mono- or combination therapy. Mixed-effects regression models evaluated the impact of treatment on Clinical Disease Activity Index (CDAI), patient-reported outcomes, and disproportionate pain (DP). Unadjusted and covariate-adjusted effects were reported. Results Patients initiating IL-6Ri (n = 286) vs TNFi monotherapy (n = 737) were older, had a longer RA history and higher baseline CDAI, and were more likely to initiate as third-line therapy; IL-6Ri (n = 401) vs TNFi (n = 1315) combination therapy initiators had higher baseline CDAI and were more likely to initiate as third-line therapy. No significant differences were noted in the outcomes between TNFi and IL-6Ri initiators (as mono- or combination therapy). Conclusion This observational study showed no significant differences in outcomes among b/ts-experienced TNFi vs IL-6Ri initiators, as either mono- or combination therapy. These findings were in contrast with the previous RCTs in biologic-naïve patients and could be explained by the differences in the patient characteristics included in this study. Further studies are needed to help understand the reasons for this discrepancy in the real-world b/ts-experienced population. Key Points• Patients with rheumatoid arthritis (RA) often require switching between biologics or targeted synthetic (b/ts) disease-modifying anti-rheumatic drugs (DMARDs) to achieve their treatment target.• Head-to-head randomized controlled trials (RCTs) in biologic-naïve RA patients with high disease activity and inadequate response/intolerance to methotrexate have shown interleukin-6 receptor inhibitors (IL-6Ri) to be superior to tumor necrosis factor inhibitors (TNFi) as monotherapy; however, there are no RCTs comparing these therapies in a population previously treated with b/tsDMARDs (i.e., b/ts-experienced patients).• This observational study compared the effectiveness of TNFi vs IL-6Ri (as mono- or combination therapy) in b/ts-experienced RA patients with moderate or high disease activity and found no significant differences in clinical outcomes for the two treatments.• A discrepancy is noted between our study and RCTs, which have shown superiority of IL-6Ri therapy (albeit in biologic-naïve patients). Further analyses may help elucidate the reason for this discrepancy in the real-world b/ts-experienced population.
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- 2023
32. Stricter treat-to-target in RA does not result in less radiographic progression
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Sofia Ramiro, Robert Landewé, Désirée van der Heijde, Alexandre Sepriano, Oliver FitzGerald, Mikkel Østergaard, Joanne Homik, Ori Elkayam, J Carter Thorne, Maggie J Larché, Gianfranco Ferraccioli, Marina Backhaus, Gilles Boire, Bernard Combe, Thierry Schaeverbeke, Alain Saraux, Maxime Dougados, Maurizio Rossini, Marcello Govoni, Luigi Sinigaglia, Alain G Cantagrel, Cornelia F Allaart, Cheryl Barnabe, Clifton O Bingham, Dirkjan van Schaardenburg, Hilde B Hammer, Rana Dadashova, Edna Hutchings, Joel Paschke, and Walter P Maksymowych
- Subjects
rheumatoid arthritis ,treat-to-target ,Rheumatology ,radiographic progression ,Pharmacology (medical) ,outcomes ,RA - Abstract
Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy. Methods Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations. Results In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: −0.04, 0.33) for 2 vs 0 visits; and +0.08 units (−0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval. Conclusions In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.
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- 2023
33. Pathogenesis of chronic chikungunya arthritis: resemblances and links with rheumatoid arthritis
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J. Kennedy Amaral, Clifton O. Bingham, Peter C. Taylor, Luis M. Vilá, Michael E. Weinblatt, and Robert T. Schoen
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Infectious Diseases ,Public Health, Environmental and Occupational Health - Abstract
Chikungunya virus (CHIKV) infection results from transmission by the mosquito vector. Following an incubation period of 5-7 days, patients develop an acute febrile illness, chikungunya fever (CHIKF), characterized by high fevers, maculopapular rash, headaches, polyarthritis/arthralgias, myalgias, nausea, vomiting, and diarrhea. Joint pain is often severe, and most often involves the hands, the wrists, the ankles, and the metatarsal-phalangeal joints of the feet. Many patients recover within several weeks, but up to 50% develop chronic joint pain and swelling for more than 12 weeks, then we refer to these symptoms as chronic chikungunya arthritis (CCA). The pathogenesis of CCA is not well understood. In this article, we suggest that mesenchymal stem cells (MSCs) may play an important role in this pathogenesis. This heterogeneous group of multipotent cells, morphologically similar to fibroblasts, may undergo epigenetic changes capable of generating aberrant progenies. However, we believe that there is no need for a latent infection. In our pathogenic hypothesis, CHIKV infection of MSCs would cause epigenetic changes both in MSCs themselves and in their progenies, without the need for reactivation of dormant viruses.
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- 2023
34. PROMIS Provides a Broader Overview of Health-related Quality of Life Than the ESSPRI in Evaluation of Sjögren Syndrome
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Dana D. DiRenzo, Susan Robinson, Clifton O. Bingham, Alan N. Baer, and Thomas Grader-Beck
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Adult ,Cross-Sectional Studies ,Sjogren's Syndrome ,Rheumatology ,Immunology ,Quality of Life ,Humans ,Pain ,Immunology and Allergy ,Patient Reported Outcome Measures ,Article ,Fatigue ,Information Systems - Abstract
ObjectiveSjögren syndrome (SS) has a significant impact on health-related quality of life (HRQOL). We sought to evaluate how the Patient Reported Outcome Measurement Information System (PROMIS) domains in SS may supplement the European League Against Rheumatism (EULAR) Sjögren Syndrome Patient Reported Index (ESSPRI).MethodsA cross-sectional evaluation was performed on consecutive adult patients during visits to an SS clinic between March 2018 and February 2020. Each patient completed PROMIS short forms related to HRQOL and the ESSPRI, and had a clinical assessment. Patients were either classified as SS by 2016 American College of Rheumatology (ACR)/EULAR criteria, or as “sicca not otherwise specified (NOS)” and used as a comparison group. Univariable and multivariable linear regression models were used to evaluate predictors of PROMIS fatigue (-F), pain interference (-PI), and ability to participate in social roles and activities (-APS).ResultsTwo hundred twenty-seven patients with SS and 85 with sicca NOS were included and did not differ in ESSPRI domains; 26% of the SS and 20% of the sicca NOS group had concurrent autoimmune disease. In SS, PROMIS-PI, PROMIS-F, and PROMIS physical function were at least one-half SD worse than US population normative values. PROMIS-PI (r = 0.73) and PROMIS-F (r = 0.80) were highly correlated with ESSPRI pain and fatigue subdomains. Fatigue and pain interference, but not dryness or mood disturbance, were the strongest predictors of social participation in multivariable analysis.ConclusionIn our SS cohort, PROMIS instruments identified a high disease burden of pain interference, fatigue, and physical function. PROMIS-F strongly predicted PROMIS-APS. PROMIS-PI and PROMIS-F scores correlated highly with their respective ESSPRI domains. PROMIS instruments should be considered to identify relevant HRQOL patterns in SS.
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- 2022
35. Maintenance of Patient-Reported Outcomes in Baricitinib-Treated Patients with Moderate-to-Severe Active Rheumatoid Arthritis: Post Hoc Analyses from Two Phase 3 Trials
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Dalton, Sholter, Jianmin, Wu, Bochao, Jia, Hong, Zhang, Kirstin, Griffing, Julie, Birt, Paulo Jorge Simoes, Reis, Huaxiang, Liu, and Clifton O, Bingham
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Rheumatology ,Immunology and Allergy - Abstract
Baricitinib has been shown to improve patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) who are inadequate responders (IR) to conventional synthetic and biologic disease-modifying antirheumatic drugs (csDMARDs and bDMARDs, respectively). We assessed the ability of baricitinib 2-mg to maintain minimal clinically important differences (MCIDs) in PROs until week 24 among week 4 and 12 responders.Data were from two phase 3 trials, RA-BUILD (NCT01721057; csDMARD-IR patients) and RA-BEACON (NCT01721044; bDMARD-IR patients). PROs included Pain Visual Analogue Scale, Health Assessment Questionnaire-Disability Index, Functional Assessment of Chronic Illness Therapy-Fatigue, Short-Form 36 Physical Component Score, and Patient's Global Assessment of Disease Activity. Outcomes were evaluated by proportions of patients achieving MCID improvements, number needed to treat (NNT) at weeks 4, 12, and 24, proportions of patients maintaining MCID responses at week 24 among week 4 or 12 responders, and median time to achieve substantial response with baricitinib 2-mg versus placebo.A higher proportion of baricitinib-treated patients achieved MCID improvements, with NNTs ranging from 5 to 8 for baricitinib 2-mg versus placebo at week 24. Generally, early MCID responses in PROs at weeks 4 or 12 were better maintained through week 24 in RA patients treated with baricitinib 2-mg versus placebo. Patients treated with baricitinib 2-mg also achieved substantial PRO responses or normative values more quickly than placebo.These results suggest baricitinib-treated patients with RA achieving MCID improvement in PROs at weeks 4 and 12 maintained those improvements over time and that substantial PRO responses were achieved quickly.
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- 2022
36. The evolution of instrument selection for inclusion in core outcome sets at OMERACT
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Zahi Touma, George A. Wells, Peter Tugwell, Shawna Grosskleg, Maarten Boers, Sarah L. Mackie, Lara J Maxwell, Christopher Hill, Catherine Hofstetter, Andrea S. Doria, Dorcas E. Beaton, Philip G. Conaghan, Beverley Shea, Robin Christensen, Clifton O. Bingham, Alexa Meara, Féline P B Kroon, Ernest Choy, Ying Ying Leung, Annelies Boonen, Maria Antonietta D'Agostino, Epidemiology and Data Science, AII - Inflammatory diseases, APH - Methodology, Interne Geneeskunde, MUMC+: MA Reumatologie (9), and RS: CAPHRI - R3 - Functioning, Participating and Rehabilitation
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musculoskeletal diseases ,Diagnostic Imaging ,Settore MED/16 - REUMATOLOGIA ,GUIDELINES ,Outcome (game theory) ,Instrument selection ,RESPONSIVENESS ,Documentation ,Rheumatology ,Outcome Assessment, Health Care ,Medicine ,Humans ,Selection algorithm ,Selection (genetic algorithm) ,Information retrieval ,business.industry ,OF-LIFE INSTRUMENTS ,Methodology ,OMERACT ,Outcome measurement instruments ,humanities ,Core (game theory) ,Anesthesiology and Pain Medicine ,Filter (video) ,Core outcome sets ,Observational study ,business ,Inclusion (education) ,CLINICAL-TRIALS ,Rheumatic and musculoskeletal diseases - Abstract
INTRODUCTION: OMERACT uses an evidence-based framework known as the 'OMERACT Filter Instrument Selection Algorithm' (OFISA) to guide decisions in the assessment of outcome measurement instruments for inclusion in a core outcome set for interventional and observational clinical trials.METHODS: A group of OMERACT imaging and patient-centered outcome methodologists worked with imaging outcome groups to facilitate the selection of imaging outcome measurement instruments using the OFISA approach. The lessons learned from this work influenced the evolution to Filter 2.2 and necessitated changes to OMERACT's documentation and processes.RESULTS: OMERACT has revised documentation and processes to incorporate the evolution of instrument selection to Filter 2.2. These revisions include creation of a template for detailed definitions of the target domain which is a necessary first step for instrument selection, modifications to the Summary of Measurement Properties (SOMP) table to account for sources of variability, and development of standardized reporting tables for each measurement property.CONCLUSIONS: OMERACT Filter 2.2 represents additional modifications of the OMERACT guide for working groups in their rigorous assessment of measurement properties of instruments of various types, including imaging outcome measurement instruments. Enhanced reporting aims to increase the transparency of the evidence base leading to judgements for the endorsement of instruments in core outcome sets.
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- 2021
37. Predicting Disease Activity in Rheumatoid Arthritis with the Fibromyalgia Survey Questionnaire: Does the Severity of Fibromyalgia Symptoms Matter?
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Alexander M. Gorzewski, Andrew C. Heisler, Tuhina Neogi, Lutfiyya N. Muhammad, Jing Song, Dorothy Dunlop, Clifton O. Bingham, Marcy B. Bolster, Daniel J. Clauw, Wendy Marder, and Yvonne C. Lee
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Rheumatology ,Immunology ,Immunology and Allergy - Abstract
ObjectiveTo determine if the degree of baseline fibromyalgia (FM) symptoms in patients with rheumatoid arthritis (RA), as indicated by the Fibromyalgia Survey Questionnaire (FSQ) score, predicts RA disease activity after initiation or change of a disease-modifying antirheumatic drug (DMARD).MethodsOne hundred ninety-two participants with active RA were followed for 12 weeks after initiation or change of DMARD therapy. Participants completed the FSQ at the initial visit. The Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) was measured at baseline and follow-up to assess RA disease activity. We evaluated the association between baseline FSQ score and follow-up DAS28-CRP. As a secondary analysis, we examined the relationship between the 2 components of the FSQ, the Widespread Pain Index (WPI) and Symptom Severity Scale (SSS), with follow-up DAS28-CRP. Multiple linear regression analyses were performed, adjusting for clinical and demographic variables.ResultsIn multiple linear regression models, FSQ score was independently associated with elevated DAS28-CRP scores 12 weeks after DMARD initiation (B = 0.04,P= 0.01). In secondary analyses, the WPI was significantly associated with increased follow-up DAS28-CRP scores (B = 0.08,P= 0.001), whereas the SSS was not (B = −0.03,P= 0.43).ConclusionHigher levels of FM symptoms weakly predicted worse disease activity after treatment. The primary factor that informed the FSQ’s prediction of disease activity was the spatial extent of pain, as measured by the WPI.
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- 2022
38. Baseline serum levels of cross-linked carboxy-terminal telopeptide of type I collagen predict abatacept treatment response in methotrexate-naive, anticitrullinated protein antibody-positive patients with early rheumatoid arthritis
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Chun Wu, Yanhua Hu, Peter Schafer, Sean E Connolly, Robert Wong, Signe Holm Nielsen, Anne-Christine Bay-Jensen, Paul Emery, Yoshiya Tanaka, Vivian P Bykerk, Clifton O Bingham, Thomas WJ Huizinga, Roy Fleischmann, and Jinqi Liu
- Subjects
Abatacept ,Methotrexate ,Rheumatology ,Arthritis ,Rheumatoid ,Immunology ,Immunology and Allergy ,Anti-Citrullinated Protein Antibodies - Abstract
ObjectiveTo investigate correlations between biomarkers of bone remodelling and extracellular matrix turnover with baseline disease activity and treatment response in patients with early rheumatoid arthritis (RA).MethodsAssessingVeryEarlyRheumatoid arthritisTreatment-2 (AVERT-2;NCT02504268) included disease-modifying antirheumatic drug-naive, anti-citrullinated protein antibody (ACPA)-positive patients randomised to weekly subcutaneous abatacept+methotrexate (MTX) or abatacept placebo+MTX for 56 weeks. This post hoc exploratory subanalysis assessed the association between baseline disease activity and eight biomarkers (Spearman’s correlation coefficient), and whether baseline biomarkers (continuous or categorical variables) could predict treatment response at weeks 24 and 52 (logistic regression).ResultsPatient characteristics were similar between overall (n=752) and biomarker subgroup (n=535) populations and across treatments. At baseline, neoepitopes of matrix metalloproteinase-mediated degradation products of types III and IV collagen and of C reactive protein (CRP) showed the greatest correlations with disease activity; cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) showed weak correlation. Only CTX-I predicted treatment response; baseline CTX-I levels were significantly associated with achieving Simplified Disease Activity Index remission and Disease Activity Score in 28 joints (DAS28 (CRP)) ConclusionIn MTX-naive, ACPA-positive patients with early RA, baseline CTX-I predicted treatment response to abatacept+MTX but not abatacept placebo+MTX.
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- 2022
39. Fibromyalgianess and glucocorticoid persistence among patients with rheumatoid arthritis
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Dorothy D. Dunlop, Yvonne C. Lee, Clifton O. Bingham, Beth I Wallace, Tuhina Neogi, Andrew C. Heisler, Meriah N Moore, Jing Song, Lutfiyya N. Muhammad, Daniel J. Clauw, Wendy Marder, Alyssa Wohlfahrt, and Marcy B. Bolster
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Fibromyalgia ,Logistic regression ,Arthritis, Rheumatoid ,Rheumatology ,Prednisone ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Glucocorticoids ,business.industry ,Odds ratio ,Clinical Science ,medicine.disease ,humanities ,Confidence interval ,Antirheumatic Agents ,Rheumatoid arthritis ,business ,Serostatus ,Glucocorticoid ,medicine.drug - Abstract
Objectives Over one-third of patients with RA exhibit evidence of fibromyalgianess, which is associated with higher rates of disability and inadequate responsiveness to RA treatment. Patients with RA often remain on glucocorticoids long-term, despite the known risk of dose-dependent morbidity. We undertook this study to examine the relationship between fibromyalgianess and glucocorticoid persistence among RA patients. Methods We followed participants with active RA on oral prednisone for ∼3 months after initiating a new DMARD. Fibromyalgianess was measured using the Fibromyalgia Survey Questionnaire (FSQ), previously shown to correlate with key FM features often superimposed upon RA. Severity of fibromyalgianess was stratified as follows: FSQ 10 high/very high. The association between baseline fibromyalgianess and glucocorticoid persistence, defined as prednisone use at 3-month follow-up visit after DMARD initiation, was assessed using multiple logistic regression adjusted for baseline demographics, RA duration, serostatus and inflammatory activity assessed using swollen joint count and CRP. Results Of the 97 participants on prednisone at baseline, 65% were still taking prednisone at follow-up. Fifty-seven percent of participants with low baseline fibromyalgianess had persistent glucocorticoid use, compared with 84% of participants with high or very high fibromyalgianess. After adjustment for non-inflammatory factors and inflammatory activity, participants with high/very high baseline fibromyalgianess were more likely to be taking prednisone at follow-up relative to those with low fibromyalgianess [odds ratio 4.99 (95% CI 1.20, 20.73)]. Conclusion High fibromyalgianess is associated with persistent glucocorticoid use, independent of inflammatory activity.
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- 2021
40. 2022 American College of Rheumatology Guideline for Vaccinations in Patients With Rheumatic and Musculoskeletal Diseases
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Anne R. Bass, Eliza Chakravarty, Elie A. Akl, Clifton O. Bingham, Leonard Calabrese, Laura C. Cappelli, Sindhu R. Johnson, Lisa F. Imundo, Kevin L. Winthrop, Reuben J. Arasaratnam, Lindsey R. Baden, Roberta Berard, S. Louis Bridges, Jonathan T. L. Cheah, Jeffrey R. Curtis, Polly J. Ferguson, Ida Hakkarinen, Karen B. Onel, Grayson Schultz, Vidya Sivaraman, Benjamin J. Smith, Jeffrey A. Sparks, Tiphanie P. Vogel, Eleanor Anderson Williams, Cassandra Calabrese, Joanne S. Cunha, Joann Fontanarosa, Miriah C. Gillispie‐Taylor, Elena Gkrouzman, Priyanka Iyer, Kimberly S. Lakin, Alexandra Legge, Mindy S. Lo, Megan M. Lockwood, Rebecca E. Sadun, Namrata Singh, Nancy Sullivan, Herman Tam, Marat Turgunbaev, Amy S. Turner, and James Reston
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy ,Article - Abstract
OBJECTIVE. To provide evidence-based recommendations on the use of vaccinations in children and adults with rheumatic and musculoskeletal diseases (RMDs). METHODS. This guideline follows American College of Rheumatology (ACR) policy guiding management of conflicts of interest and disclosures and the ACR guideline development process, which includes the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. It also adheres to the Appraisal of Guidelines for Research and Evaluation (AGREE) criteria. A core leadership team consisting of adult and pediatric rheumatologists and a guideline methodologist drafted clinical population, intervention, comparator, outcomes (PICO) questions. A review team performed a systematic literature review for the PICO questions, graded the quality of evidence, and produced an evidence report. An expert Voting Panel reviewed the evidence and formulated recommendations. The panel included adult and pediatric rheumatology providers, infectious diseases specialists, and patient representatives. Consensus required ≥70% agreement on both the direction and strength of each recommendation. RESULTS. This guideline includes expanded indications for some vaccines in patients with RMDs, as well as guidance on whether to hold immunosuppressive medications or delay vaccination to maximize vaccine immunogenicity and efficacy. Safe approaches to the use of live attenuated vaccines in patients taking immunosuppressive medications are also addressed. Most recommendations are conditional and had low quality of supporting evidence. CONCLUSION. Application of these recommendations should consider patients’ individual risk for vaccine-preventable illness and for disease flares, particularly if immunosuppressive medications are held for vaccination. Shared decision-making with patients is encouraged in clinical settings.
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- 2022
41. 'From Where I Stand': using multiple anchors yields different benchmarks for meaningful improvement and worsening in the rheumatoid arthritis flare questionnaire (RA-FQ)
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Susan J, Bartlett, Vivian P, Bykerk, Orit, Schieir, Marie-France, Valois, Janet E, Pope, Gilles, Boire, Carol, Hitchon, Glen, Hazlewood, Louis, Bessette, Edward, Keystone, Carter, Thorne, Diane, Tin, Clifton O, Bingham, and M, Zummer
- Abstract
The Rheumatoid Arthritis Flare Questionnaire (RA-FQ) is a patient-reported measure of disease activity in RA. We estimated minimal and meaningful change from the perspective of RA patients, physicians, and using a disease activity index.Data were from 3- to 6-month visits of adults with early RA enrolled in the Canadian Early Arthritis Cohort. Participants completed the RA-FQ, the Patient Global Assessment of RA, and the Patient Global Change Impression at consecutive visits. Rheumatologists recorded joint counts and MD Global. Clinical Disease Activity Index (CDAI) scores were computed. We compared mean RA-FQ change across categories using patients, physicians, and CDAI anchors.The 808 adults were mostly white (84%) women (71%) with a mean age of 55 and moderate-high disease activity (85%) at enrollment. At V2, 79% of patients classified their RA as changed; 59% were better and 20% were worse. Patients reporting they were a lot worse had a mean RA-FQ increase of 8.9 points, whereas those who were a lot better had a -6.0 decrease. Minimal worsening and improvement were associated with a mean 4.7 and - 1.8 change in RA-FQ, respectively, while patients rating their RA unchanged had stable scores. Physician and CDAI classified more patients as worse than patients, and minimal and meaningful RA-FQ thresholds differed by group.Thresholds to identify meaningful change vary by anchor used. These data offer new evidence demonstrating robust psychometric properties of the RA-FQ and offer guidance about improvement or worsening, supporting its use in RA care, research, and decision-making.
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- 2022
42. Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis
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Anne R Bass, Noha Abdel-Wahab, Pankti D Reid, Jeffrey A Sparks, Cassandra Calabrese, Deanna P Jannat-Khah, Nilasha Ghosh, Divya Rajesh, Carlos Andres Aude, Lydia Gedmintas, Lindsey MacFarlane, Senada Arabelovic, Adewunmi Falohun, Komal Mushtaq, Farah Al Haj, Adi Diab, Ami A Shah, Clifton O Bingham, Karmela Kim Chan, and Laura C Cappelli
- Subjects
Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
ObjectivesTo compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA).MethodsThe retrospective multicentre observational study included patients with a diagnosis of ICI-IA treated with a tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX); patients with pre-existing autoimmune disease were excluded. The primary outcome was time to cancer progression from ICI initiation; the secondary outcome was time to arthritis control from DMARD initiation. Cox proportional hazard models were used to compare medication groups, adjusting for confounders.Results147 patients were included (mean age 60.3 (SD 11.9) years, 66 (45%) women). ICI-IA treatment was TNFi in 33 (22%), IL6Ri 42 (29%) and MTX 72 (49%). After adjustment for time from ICI initiation to DMARD initiation, time to cancer progression was significantly shorter for TNFi compared with MTX (HR 3.27 (95% CI 1.21 to 8.84, p=0.019)) while the result for IL6Ri was HR 2.37 (95% CI 0.94 to 5.98, p=0.055). Time to arthritis control was faster for TNFi compared with MTX (HR 1.91 (95% CI 1.06 to 3.45, p=0.032)) while the result for IL6Ri was HR 1.66 (95% CI 0.93 to 2.97, p=0.089). A subset analysis in patients with melanoma gave similar results for both cancer progression and arthritis control.ConclusionThe treatment of ICI-IA with a biologic DMARD is associated with more rapid arthritis control than with MTX, but may be associated with a shorter time to cancer progression.
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- 2023
43. Conversion of Functional Assessment of Chronic Illness Therapy–Fatigue to Patient‐Reported Outcomes Measurement Information System Fatigue Scores in Two Phase III Baricitinib Rheumatoid Arthritis Trials
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David Cella, Carol L Kannowski, Clifton O. Bingham, Amy M. DeLozier, Susan J. Bartlett, and Luna Sun
- Subjects
Adult ,Male ,Patient-Reported Outcomes Measurement Information System ,medicine.medical_specialty ,Time Factors ,Baricitinib ,Standard score ,Placebo ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Predictive Value of Tests ,Health Status Indicators ,Humans ,Janus Kinase Inhibitors ,Multicenter Studies as Topic ,Medicine ,Patient Reported Outcome Measures ,Fatigue ,Aged ,Randomized Controlled Trials as Topic ,030203 arthritis & rheumatology ,Sulfonamides ,business.industry ,Remission Induction ,Scoring methods ,Middle Aged ,medicine.disease ,humanities ,Clinical trial ,Treatment Outcome ,Clinical Trials, Phase III as Topic ,Purines ,Antirheumatic Agents ,Rheumatoid arthritis ,Chronic Disease ,Physical therapy ,Azetidines ,Pyrazoles ,Female ,Active treatment ,business - Abstract
OBJECTIVE The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is validated for measuring fatigue in rheumatoid arthritis (RA). However, 10 of 13 FACIT-F items are identified as relevant to patients with RA. The Patient-Reported Outcomes Measurement Information System (PROMIS) uses an item response theory-calibrated T score metric. The PROMIS Fatigue item bank includes the FACIT-F items, enabling score conversion. The performance of converted PROMIS Fatigue scores has not been evaluated in RA populations or clinical trials. Our objective was to assess the performance of converted PROMIS Fatigue scores in 2 RA clinical trials of baricitinib. METHODS Crosswalk tables and pattern-scoring methods converted FACIT-F scores to PROMIS Fatigue for both the 13-item FACIT-F and the 10-item RA-optimized FACIT-F instrument, in 2 RA clinical trials evaluating baricitinib, RA-BEAM, and RA-BEACON. RA-BEAM patients had an inadequate response to methotrexate. RA-BEACON patients had an inadequate response or intolerance to ≥1 tumor necrosis factor inhibitor. Baricitinib was compared to all treatment arms via analysis of covariance on PROMIS Fatigue score conversions. RESULTS Baseline FACIT-F-derived PROMIS Fatigue scores reflected severe fatigue across treatment groups and were similar using different scoring methods. At week 24 in both studies, baricitinib was associated with clinically meaningful improvements in PROMIS Fatigue scores. PROMIS Fatigue scores were consistent for conversion methods and for the 13-item or 10-item FACIT-F. CONCLUSION All 4 conversion methods showed differentiation of active treatment compared with placebo from week 12, supporting the use of the PROMIS Fatigue and converting the 10-item FACIT-F to assess fatigue and demonstrate treatment benefit in RA clinical trials on a standardized metric.
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- 2021
44. Patients and clinicians define symptom levels and meaningful change for PROMIS pain interference and fatigue in RA using bookmarking
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Susan J. Bartlett, Anne Lyddiatt, Clifton O. Bingham, Mary Suzanne Schrandt, Alessandra Butanis, Michelle Jones, Karon F. Cook, Ana Maria Orbai, Vivian P. Bykerk, and Victoria Ruffing
- Subjects
Adult ,Male ,medicine.medical_specialty ,Patient-Reported Outcomes Measurement Information System ,Pain Interference ,Severity of Illness Index ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Patient Reported Outcome Measures ,030212 general & internal medicine ,Fatigue ,Aged ,Pain Measurement ,030203 arthritis & rheumatology ,business.industry ,Bookmarking ,Lived experience ,Perspective (graphical) ,Middle Aged ,Clinical Science ,Social engagement ,Treatment efficacy ,Methotrexate ,Treatment Outcome ,Antirheumatic Agents ,Physical therapy ,Female ,Symptom Assessment ,business - Abstract
Objectives Using patient-reported outcomes to inform clinical decision-making depends on knowing how to interpret scores. Patient-Reported Outcome Measurement Information System® (PROMIS®) instruments are increasingly used in rheumatology research and care, but there is little information available to guide interpretation of scores. We sought to identify thresholds and meaningful change for PROMIS Pain Interference and Fatigue scores from the perspective of RA patients and clinicians. Methods We developed patient vignettes using the PROMIS item banks representing a continuum of Pain Interference and Fatigue levels. During a series of face-to-face ‘bookmarking’ sessions, patients and clinicians identified thresholds for mild, moderate and severe levels of symptoms and identified change deemed meaningful for making treatment decisions. Results In general, patients selected higher cut points to demarcate thresholds than clinicians. Patients and clinicians generally identified changes of 5–10 points as representing meaningful change. The thresholds and meaningful change scores of patients were grounded in their lived experiences having RA, approach to self-management, and the impacts on function, roles and social participation. Conclusion Results offer new information about how both patients and clinicians view RA symptoms and functional impacts. Results suggest that patients and providers may use different strategies to define and interpret RA symptoms, and select different thresholds when describing symptoms as mild, moderate or severe. The magnitude of symptom change selected by patients and clinicians as being clinically meaningful in interpreting treatment efficacy and loss of response may be greater than levels determined by external anchor and statistical methods.
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- 2021
45. Understanding Differences in Patient Descriptions of Rheumatoid Arthritis Flares Using OMERACT Core Domains
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Gabriela L. Maica, Christine Iannaccone, Vivi Feathers, Michelle L. Frits, Vivian P. Bykerk, Clifton O. Bingham, Michael Weinblatt, and Nancy A. Shadick
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Rheumatology ,Immunology ,Immunology and Allergy - Abstract
ObjectiveRecently, there has been consensus on domains that constitute flares in rheumatoid arthritis (RA); however, variations in patients' flare descriptions continue to be observed. This study evaluates how demographic and clinical characteristics influence these differences.MethodsParticipants enrolled in a prospective RA registry completed a qualitative survey that included the open-ended question "What does a flare mean to you?" Responses were categorized into Outcome Measures in Rheumatology (OMERACT) core and research domains. Univariate analyses evaluated demographic and clinical characteristics. Regression analyses determined independent variables associated with flare description variations.ResultsAmong 645 participants, the median Disease Activity Score in 28 joints (DAS28) with C-reactive protein was 2.1 (IQR 1.6-2.9); 58% of the participants reported at least 1 flare in the past 6 months. Participants reported a median of 3 (IQR 2-5) OMERACT domains when describing flares. Fatigue was more commonly noted among females (odds ratio [OR] 6.12;P< 0.001). Older participants were less likely to report emotional distress (OR 0.97;P= 0.03), swollen joints (OR 0.99;P= 0.04), physical function decrease (OR 0.98;P= 0.02), and a general increase in RA symptoms (OR 0.98;P= 0.005). Participants with a higher DAS28 score were less likely to report symptoms of stiffness (OR 0.70;P= 0.009), and those who experienced a flare within the last 6 months were more likely to describe flares as pain (OR 2.53;P< 0.001) and fatigue (OR 2.00;P= 0.007).ConclusionVariations in patients' flare descriptions can be driven by a patient's disease activity, the experience of a recent flare, as well as different demographic characteristics, such as age and gender. Understanding the interplay of these characteristics can guide a physician's approach to the management of patients' RA flares.
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- 2023
46. Identification of outcome domains in immune checkpoint inhibitor-induced inflammatory arthritis and polymyalgia rheumatica: A scoping review by the OMERACT irAE working group
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Nilasha Ghosh, Nina Couette, Wouter H. van Binsbergen, Sophia C. Weinmann, Bridget Jivanelli, Beverley Shea, Anne R. Bass, Karolina Benesova, Clifton O. Bingham, Cassandra Calabrese, Laura C. Cappelli, Karmela Kim Chan, Ernest Choy, Dimitrios Daoussis, Susan Goodman, Marie Hudson, Shahin Jamal, Jan Leipe, Maria A. Lopez-Olivo, Maria Suarez-Almazor, Conny J. van der Laken, Alexa Simon Meara, David Liew, and Marie Kostine
- Subjects
Anesthesiology and Pain Medicine ,Rheumatology - Abstract
Introduction: Immune checkpoint inhibitors (ICI), increasingly used cancer therapeutics, can cause off-target inflammatory effects called immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis (ICI-induced IA) and polymyalgia rheumatica (ICI-induced PMR). There are no validated classification criteria or outcome measures for these conditions, and adaptation of treatment recommendations from corresponding rheumatic diseases may not be appropriate. We summarized clinical descriptors of ICI-induced IA and ICI-induced PMR and aggregated domains used for these conditions in order to inform the development of a core set of outcome domains. Methods: As the initial step of the core domain set generation process, we systemically searched Medline (Pubmed), EMBASE, Cochrane, and CINHL through March 2021 to identify all studies that provide both clinical descriptions and domains relevant to ICI-induced IA and ICI-induced PMR. Domains were mapped to core areas, such as pathophysiological manifestations, life impact, resource use, and longevity/survival, as suggested by the OMERACT 2.1 Filter. Results: We identified 69 publications, over a third of which utilized non-specific diagnoses of “arthritis,” “arthralgia,” and/or “PMR”. Other publications provided the number, the distribution and/or names of specific joints affected, while others labeled the irAE as the corresponding rheumatic disease, such as rheumatoid arthritis or spondyloarthritis. Most distinct domains mapped to the pathophysiology/manifestations core area (24 domains), such as signs/symptoms (13 domains), labs (6 domains), and imaging (5 domains), with harm domains of adverse effects from irAE treatment and fear of irAE treatment decreasing ICI efficacy. Forty-three publications also referenced irAE treatment and 35 subsequent response, as well as 32 tumor response. Conclusion: There is considerable heterogeneity in the domains used to clinically characterize ICI-induced IA and ICI-induced PMR. There were several domains mapped to the pathophysiologic manifestations core area, although several publications highlighted domains evenly distributed among the other core areas of life impact, longevity/survival and resource use.
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- 2023
47. Association of Dysregulated Central Pain Processing and Response to Disease–Modifying Antirheumatic Drug Therapy in Rheumatoid Arthritis
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Clifton O. Bingham, Andrew C. Heisler, Dorothy D. Dunlop, Wendy Marder, Daniel J. Clauw, Alyssa Wohlfahrt, Jing Song, Marcy B. Bolster, Lutfiyya N. Muhammad, Yvonne C. Lee, and Tuhina Neogi
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Adult ,Male ,Pain Threshold ,medicine.medical_specialty ,medicine.medical_treatment ,Immunology ,Pain ,Arthritis ,Summation ,Logistic regression ,Article ,Arthritis, Rheumatoid ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,Disease-modifying antirheumatic drug ,Aged ,Pain Measurement ,030203 arthritis & rheumatology ,Central Nervous System Sensitization ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Antirheumatic Agents ,Rheumatoid arthritis ,Female ,business ,030217 neurology & neurosurgery ,Rheumatism - Abstract
Objective To determine the association between dysregulated central pain processing and treatment response in rheumatoid arthritis (RA). Methods One hundred eighty-two participants with active RA were followed up for 12 weeks after starting a disease-modifying antirheumatic drug (DMARD). To assess central pain processing, participants underwent quantitative sensory testing (QST), including assessment of pressure pain thresholds (PPTs) at the trapezius muscles, temporal summation, and conditioned pain modulation (CPM). QST measures were categorized as high central dysregulation versus low central dysregulation. The association between baseline central dysregulation and treatment response, as defined by the European League Against Rheumatism (EULAR) response criteria, was assessed using multiple logistic regression adjusted for demographic characteristics, RA-related variables, and psychosocial variables. Results A good EULAR response was achieved in fewer participants with high CPM dysregulation than participants with low CPM dysregulation (22.5% versus 40.3%; P = 0.01). A similar trend, though not significant, was noted when central dysregulation was assessed with PPT and temporal summation. The adjusted odds ratios (ORs) for the association between high central dysregulation and good EULAR response were 0.59 for PPTs (95% confidence interval [95% CI] 0.28-1.23), 0.60 for temporal summation (95% CI 0.27-1.34), and 0.40 for CPM (95% CI 0.19-0.83). In a model examining the combined effects of dysregulated temporal summation and CPM, dysregulation of both measures was associated with lower odds of achieving a good EULAR response (OR 0.23 [95% CI 0.07-0.73]). Conclusion Low CPM was significantly associated with lower odds of achieving a good EULAR response, suggesting that inefficient descending inhibitory mechanisms may be a potential treatment target for further study.
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- 2020
48. What Does the Patient Global Health Assessment in Rheumatoid Arthritis Really Tell Us? Contribution of Specific Dimensions of Health‐Related Quality of Life
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Ethan T. Craig, Jeffrey R. Curtis, Scott L. Zeger, Susan J. Bartlett, Clifton O. Bingham, Vivian P. Bykerk, and Jamie Perin
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Adult ,Disease ,Article ,Arthritis, Rheumatoid ,Diagnostic Self Evaluation ,Disability Evaluation ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Rheumatology ,medicine ,Humans ,Patient Reported Outcome Measures ,Depression (differential diagnoses) ,Aged ,030203 arthritis & rheumatology ,Sleep disorder ,business.industry ,Middle Aged ,medicine.disease ,Mood ,Cohort ,Linear Models ,Quality of Life ,Anxiety ,Observational study ,medicine.symptom ,Factor Analysis, Statistical ,business ,Clinical psychology - Abstract
Objective To estimate the contributions of health-related quality of life domains to the patient global assessment of disease activity (PtGA) in rheumatoid arthritis (RA). Methods Data are drawn from baseline visits of 2 observational RA cohorts. Participants completed forms for patient-reported outcome measures, including PtGA and measures from the Patient-Reported Outcomes Measurement Information System, and clinical data were collected. Factor analysis was used to identify latent variables, and multivariable linear regression was used to estimate determinants of the PtGA. Results Patients were mostly female (81%), white (78%), and had established disease (mean ± SD 12.3 ± 10.7 years), with 62% in remission or having low disease activity. In cohort 1 (n = 196), the following 2 factors emerged: 1) daily function (moderate-to-strong [i.e., >|0.65|] loadings of physical function, pain interference, social participation, and fatigue, and weak [>0.35] loadings of sleep disturbance); and 2) emotional distress (strong loadings of depression and anxiety). In crude analysis, daily function explained up to 53% and emotional distress up to 20% of the variance in PtGA. In both cohorts, in adjusted analyses, daily function and, to a much lesser extent, swollen joint count independently predicted PtGA; age was inversely related to PtGA in cohort 1 only. Conclusion These findings suggest that in patients with RA, PtGA ratings largely reflect the extent to which patients feel they can function in everyday roles and are not impacted by mood. This suggests that higher than expected PtGA scores may offer an opportunity to discuss patient expectations regarding roles and activities and the impact of their RA symptoms on daily function.
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- 2020
49. Reliability and validity of PROMIS physical function, pain interference, and fatigue as patient reported outcome measures in adult idiopathic inflammatory myopathies: International study from the OMERACT myositis working group
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Dana DiRenzo, Didem Saygin, Ingrid de Groot, Clifton O. Bingham III, Ingrid E. Lundberg, Merrilee Needham, Jin Kyun Park, Malin Regardt, Catherine Sarver, Yeong Wook Song, Lara Maxwell, Dorcas Beaton, Marianne de Visser, Lisa Christopher-Stine, Christopher A. Mecoli, Helene Alexanderson, Neurology, AII - Infectious diseases, and Amsterdam Neuroscience - Neuroinfection & -inflammation
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Anesthesiology and Pain Medicine ,Rheumatology - Abstract
Objective: Pain interference, fatigue, and impaired physical function are common features of idiopathic inflammatory myopathies (IIM). The objective of this study was to evaluate the construct validity and test-retest reliability of the Patient Reported Outcome Information System (PROMIS) Pain Interference 6av1.0, Fatigue 7av1.0, and Physical Function 8bv2.0 instruments. Methods: Patient-Reported Outcome Measures (PROMs) were deployed to adult IIM patients from OMERACT Myositis Working Group (MWG) international clinic sites via two online surveys (2019, 2021). Internal consistency of each PROM was analyzed by Cronbach's α. Construct validity was determined by a priori hypotheses generated by the MWG with >75% agreement for each hypothesis and calculated with Pearson correlations. Test-retest reliability was assessed using intraclass correlation coefficient with PROMIS instruments administered at time zero and 7 days. Results: Surveys were sent to 368 participants in total; participants who completed each questionnaire varied (n=65 to 263). For construct validity, 10 out of 13 a priori hypotheses were met supporting construct validity of PROMIS instruments (Pain Interference 3/4, fatigue 4/4, and Physical Function 3/5). Test-retest reliability was strong for all PROMIS instruments. All PROMIS instruments demonstrated excellent internal consistency. None of the measures demonstrated any ceiling or floor effects except for a ceiling effect in the Pain Interference instrument. Conclusions: This study presents test-retest reliability and construct validity evidence supporting PROMIS Pain Interference (6a v1.0), Fatigue (7a v1.0), and Physical Function (8b v2.0) using a large international cohort of patients with IIM. Internal consistency of these instruments was excellent. A ceiling effect was noted in the Pain Interference instrument.
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- 2022
50. Statin use and MRI subchondral bone marrow lesion worsening in generalized osteoarthritis: longitudinal analysis from Osteoarthritis Initiative data
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Bahram Mohajer, Ali Guermazi, Philip G. Conaghan, Francis Berenbaum, Frank W. Roemer, Arya Haj-Mirzaian, Clifton O. Bingham, Kamyar Moradi, Xu Cao, Mei Wan, and Shadpour Demehri
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Male ,Knee Joint ,General Medicine ,Osteoarthritis, Knee ,Magnetic Resonance Imaging ,Article ,Bone Marrow ,Cardiovascular Diseases ,Disease Progression ,Humans ,Radiology, Nuclear Medicine and imaging ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cartilage Diseases - Abstract
OBJECTIVES: To determine the association between statin therapy and knee MRI-detected subchondral bone marrow lesion (BML) longitudinal worsening in patients with Heberden’s nodes (HNs) as the hallmark of generalized osteoarthritis (OA) phenotype. METHODS: All participants gave informed consent, and IRB approved HIPAA-compliant protocol. We assessed the worsening in BML volume and number of affected subregions in the Osteoarthritis Initiative (OAI) participants with HNs at baseline clinical examination (HN(+)), using the semi-quantitative MRI Osteoarthritis Knee Scores at baseline and 24 months. Participants were classified according to baseline BML involvement as “no/minimal” (≤2/14 knee subregions affected and maximum BML score ≤ 1) or “moderate/severe.” Statin users and non-users were selected using 1:1 propensity-score (PS) matching for OA and cardiovascular disease (CVD)–related potential confounding variables. We assessed the association between statin use and increasing BML score and affected subregions using adjusted mixed-effect regression models. RESULTS: The PS-matched HN(+) participants (63% female, aged 63.5 ± 8.5-year-old) with no/minimal and moderate/severe BML cohorts consisted of 332 (166:166, statin users: non-users) and 380 (190:190) knees, respectively. In the HN(+) participants with no/minimal BML, statin use was associated with lower odds of both BML score worsening (odds ratio, 95% confidence interval: 0.62, 0.39–0.98) and increased number of affected subregions (0.54, 0.33–0.88). There was no such association in HN(−) participants or those HN(+) participants with baseline moderate/severe BML. CONCLUSION: In patients with CVD indications for statin therapy and generalized OA phenotype (HN(+)), statin use may be protective against the OA-related subchondral bone damage only in the subgroup of participants with no/minimal baseline BML.
- Published
- 2022
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