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Background: Systemic immunomodulatory agents are indicated in the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. Perioperative use of these medications may increase the risk of surgical site infection (SSI) and complication., Objective: To evaluate the risk of SSI and complication in patients with chronic autoimmune inflammatory disease receiving immunomodulatory agents (tumor necrosis factor-alfa [TNF-α] inhibitors, interleukin [IL] 12/23 inhibitor, IL-17 inhibitors, IL-23 inhibitors, cytotoxic T-lymphocyte-associated antigen-4 costimulator, phosphodiesterase-4 inhibitor, Janus kinase inhibitors, tyrosine kinase 2 inhibitor, cyclosporine (CsA), and methotrexate [MTX]) undergoing surgery., Methods: We performed a search of the MEDLINE PubMed database of patients with chronic autoimmune inflammatory disease on immune therapy undergoing surgery., Results: We examined 48 new or previously unreviewed studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease., Conclusion: For low-risk procedures, TNF-α inhibitors, IL-17 inhibitors, IL-23 inhibitors, ustekinumab, abatacept, MTX, CsA, and apremilast can safely be continued. For intermediate- and high-risk surgery, MTX, CsA, apremilast, abatacept, IL-17 inhibitors, IL-23 inhibitors, and ustekinumab are likely safe to continue; however, a case-by-case approach is advised. Acitretin can be continued for any surgery. There is insufficient evidence to make firm recommendations on tofacitinib, upadacitinib, and deucravacitinib., Competing Interests: Conflicts of interest Dr Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alvotech, vTv Therapeutics, Bristol Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, LEO Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate, and the National Psoriasis Foundation and is a founder and part owner of Causa Research and holds stock in Sensal Health. Dr Wu is or has been an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Aristea Therapeutics, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, DermTech, Dr. Reddy’s Laboratories, Eli Lilly, EPI Health, Galderma, Janssen, LEO Pharma, Mindera, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sanofi Genzyme, Solius, Sun Pharmaceutical, UCB, and Zerigo Health. Dr Hsu has served on the advisory board for Boehringer Ingelheim, LEO Pharma, and Sanofi and has served on the registries/clinical trials for CorEvitas, PROSE, Argenx, and Cabaletta. Dr Armstrong has served as a research investigator, scientific adviser, and/or speaker to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, and Pfizer. Dr Wallace has served as a research investigator, scientific adviser, and/or speaker to Pfizer, Target RWE, Kyowa, Amgen, Arcutis, and Argenx. Dr Lee has served as a research investigator, scientific adviser, and/or speaker to Eli Lilly, Sanofi, Regeneron, Pfizer, Trevi Therapeutics, AbbVie, Mayne Pharmaceuticals, Incyte Corp, Castle Creek, Pyramid Bioscience, Amyrt, Krystal Biotech, Arcutis, Celgene, Target Pharma, Amgen, Novartis, UCB, Galderma, Kiniksa, Avita, Janssen, MoonLake Pharmaceuticals, and Timber Pharmaceuticals. Dr Merola is a consultant and/or investigator for Amgen, Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Incyte, Novartis, Janssen, UCB, Sanofi Regeneron, Sun Pharma, Biogen, Pfizer, and LEO Pharma. Dr Schwartzman has served as a speaker and/or consultant to AbbVie, Janssen, Lilly, Pfizer, UCB, Myriad, Novartis, Sanofi/Regeneron, Stelexis, Jubilant, and Teijin and has served as a board member to the National Psoriasis Foundation. Dr Gladman has received consulting fees from AbbVie, Amgen, BMS, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB and has received research support from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Dr Liu has served as a research investigator, scientific adviser, and/or speaker to for AbbVie, Janssen, Lilly, Sanofi Regeneron, Arcutis, Dermavant, Pfizer, Bristol Myers Squibb, UCB, Incyte, Amgen, and Evelo. Dr Koo has served on the advisory board/consultant for AbbVie, Arcutis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Castle, Dermavant, Incyte, Janssen, Eli Lilly, EPI, Leo, Novartis, Ortho Dermatologics/Valeant, Pfizer, Regeneron/Sanofi, Sun Pharma, and UCB. Dr Hawkes has served on the advisory board/consultant for AbbVie, Arcutis, Boehringer Ingelheim, BMS, Janssen, LearnSkin, LEO, Lilly, Novartis, Pfizer, Regeneron-Sanofi Genzyme, and UCB, has served on the medical/scientific board for the National Psoriasis Foundation and International Psoriasis Council (IPC), and has stock ownership/equity in Regeneron Pharmaceuticals. Dr Reddy has served on the advisory board/consultant UCB, Novartis, Fresenius, Amgen, AbbVie, Janssen, and Pfizer. Dr Prussick has served as a scientific adviser and/or speaker to of Amgen, Janssen, AbbVie, and Novartis and has served as a board member to the National Psoriasis Foundation. Dr Yamauchi has served as a research investigator, scientific adviser, and/or speaker to AbbVie, Amgen, Lilly, Janssen, Sun Pharma, BMS, UCB, Ortho Dermatologics, and Novartis. Dr Lewitt has received grants/research support from Novan, Galderma, Leo, Lilly, DermTech, and Amgen and has served as a speaker’s bureau/consultant/advisory board for AbbVie, Janssen, Lilly, Galderma, Pfizer, UCB, Ortho Dermatologics, Dermavant, and Bristol Myers Squibb. Dr Soung has served as a research investigator, scientific adviser, and/or speaker to Celgene, Amgen, Eli Lilly, AbbVie, Pfizer, Ortho Dermatologics, National Psoriasis Foundation (non-profit), LEO, Novartis, Regeneron/Sanofi, UCB, Janssen, Kyowa Kirin, Dermavant, Bristol Myers Squibb, Arcutis, KoBioLabs, and Castle Biosciences. Dr Weinberg has served as a speaker for AbbVie, Dermavant, Lilly, Janssen, BMS, Amgen, and UCB and has received research grants from Arcutis, Dermavant, AbbVie, UCB, Janssen, and Lilly. Dr Lebwohl is an employee of Mount Sinai, has received research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Inozyme, Janssen Research & Development, LLC, Novartis, Ortho Dermatologics, Regeneron, and UCB, Inc, and is a consultant for AnaptysBio, Arcutis, Inc, Arena Pharmaceuticals, Aristea Therapeutics, Avotres Therapeutics, BioMX, Boehringer Ingelheim, Brickell Biotech, Cara Therapeutics, Castle Biosciences, CorEvitas, Dermavant Sciences, Evommune, Inc, Facilitation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Hexima Ltd, Incyte, Meiji Seika Pharma, Mindera, National Society of Cutaneous Medicine, New York College of Podiatric Medicine, Pfizer, Seanergy, SUN Pharma, Verrica, and Vial. Dr Glick has served as a research investigator, scientific adviser, and/or speaker to AbbVie, AstraZeneca, Amgen, Janssen, Galderma, Sun Pharma, LEO Pharma, Lilly, Novartis, Dermavant Sciences, Incyte, EPI/Novan, BMS, Nimbus Lakshmi, Cara Therapeutics, Dermira, Sanofi/Genzyme, Regeneron, Pfizer, ChemoCentryx, Ortho Dermatologics, UCB, Brickell, Biotech, CorEvitas Registry PSO, CorEvitas Registry AD, PROSE Registry for AD. Dr Kircik has served as a research investigator, scientific adviser, board member, and/or speaker to Abbott Laboratories, AbbVie, Allergan, Inc, Almirall, Amgen, Inc, Arcutis, Biogen-Idec, BMS, Boehringer Ingelheim, Breckinridge Pharma, Celgene, Centocor, Inc, Cellceutix, Cipher, Combinatrix, Connetics Corporation, Coria, Dermavant, Dermira, Dow Pharmaceutical Sciences, Inc, Dr. Reddy’s Laboratories, Eli Lilly, Galderma, Genentech, Inc, GlaxoSmithKline, PLC, Idera, Johnson & Johnson, Leo, Maruho, Merck, Medicis Pharmaceutical Corp, Novartis AG, Promius, PharmaDerm, Pfizer, Serono (Merck Serono International SA), Stiefel Laboratories, Inc, Sun Pharma, Taro, UCB, Valeant Pharmaceuticals Intl, and XenoPort. Dr Desai has served on the Medical Board of the National Psoriasis Foundation and holds multiple other leadership positions in dermatologic organizations, and has served as a researcher and/or consultant for Pfizer, Lilly, AbbVie, Bristol Myers Squibb, Galderma, and other organizations. Drs James and Zaino and Author Rosenberg have no conflicts of interest to declare., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis., Objective: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines., Methods: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts., Results: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination., Limitations: Studies regarding infection rates after vaccination are lacking., Conclusion: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases., Competing Interests: Conflicts of interest Dr Chat, Dr Ellebrecht, Ms. Kingston, and Dr Cordoro have no conflicts of interest to declare. Dr Bell is an employee of the National Psoriasis Foundation. Author Gondo is an employee of the National Psoriasis Foundation. Dr Desai has served as a research investigator, consultant, speaker, and/or advisor for AbbVie, Galderma, Foundation for Research & Education of Dermatology, Almirall, Dermavant, Ferndale Laboratories, Inc, Incyte Corporation, Gore Range Capital, AOBiome, LLC, Bristol Myers Squibb, Verrica Pharmaceuticals, UCB, Ortho Dermatologics, Scientis, EPI Health, Avita, Pfizer, Lilly, LEO, Incyte Corporation, L'Oreal USA, Inc, Beiersdorf, Inc, and Johnson and Johnson; is a board member of the National Psoriasis Foundation and Women's Derm Society; and is a stockholder for Gore Range Capital. Dr Duffin has been a consultant, advisor, or served as an investigator for AbbVie, AnaptysBio, Amgen, Bristol-Myers Squib, Celgene, CorEvitas/Corrona, Boehringer-Ingelheim, Janssen, Lilly, Novartis, Ortho Dermatologica, Pfizer, Regeneron, Sienna, Stiefel, and UCB. Dr Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen Inc, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, SunPharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Valeant, Menlo, Merck & Co, Qurient Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Advance Medical, Suncare Research, Informa, UpToDate and the National Psoriasis Foundation; is the founder and majority owner of www.DrScore.com; is a founder and part owner of Causa Research; and has stock in Sensal Health. Dr Garg is an advisor for AbbVie, Aclaris Therapeutics, Anaptys Bio, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Incyte, InflaRx, Insmed, Janssen, Novartis, Pfizer, UCB, and Viela Biosciences; receives honoraria; and receives research grants from AbbVie, UCB and National Psoriasis Foundation. Dr Gelfand served as a consultant for Abbvie, BMS, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies) GSK, Happify, Lilly (DMC), Leo, Janssen Biologics, Neumentum, Novartis Corp, Pfizer, UCB (DSMB), Neuroderm (DSMB), Regeneron, Trevi, and Mindera Dx., receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from Boehringer Ingelheim, and Pfizer Inc; and received payment for continuing medical education work related to psoriasis that was supported indirectly pharmaceutical sponsors. Dr Gelfand is a co-patent holder of resiquimod for treatment of cutaneous T cell lymphoma. Dr Gelfand is a Deputy Editor for the Journal of Investigative Dermatology receiving honoraria from the Society for Investigative Dermatology, is Chief Medical Editor for Healio Psoriatic Disease (receiving honoraria) and is a member of the Board of Directors for the International Psoriasis Council, receiving no honoraria. Dr Gladman has served as a consultant for AbbVie, Amgen, BMS, Eli Lily, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB; and has received grants from AbbVie, Amgen, Eli Lily, Janssen, Novartis, Pfizer, and UCB. Dr Green is a research investigator, speaker, and/or consultant for AbbVie, Amgen, Arcutis, BMS, Dermavant, Lilly, MC2, SunPharma, and UCB. Dr Gudjonsson has served as an advisor for Novartis, Janssen, Almirall, Eli Lilly, Sanofi, and Boehringer Ingelheim; and has received research support from Almirall, Eli Lilly, Prometheus, BMS, and Janssen. Dr Han has served as a research investigator, consultant, and/or speaker for AbbVie, Amgen, Boehringer Ingelheim, BMS, Dermavant, Janssen, Lilly, UCB, Novartis, Leo Pharma, Regeneron, Sanofi Genzyme, Ortho Dermatologics, Bond Avillion, Pellepharm, MC2, Athenex, Celgene, Sun Pharma, and Pfizer. Dr Hawkes is an advisor and/or consultant for AbbVie, Arcutis, Boehringer Ingelheim, Janssen, LearnSkin, LEO, Lilly, Novartis, Pfizer, Regeneron-Sanofi Genzyme, and UCB; is a board member of the National Psoriasis Foundation; and has stock ownership/equity of Regeneron Pharmaceuticals. Dr Kircik is a research investigator, speaker, advisor, and/or consultant for Abbott Laboratories, Allergan, Almirall, Amgen, Arcutis, Biogen-Idec, BMS, Boehringer-Ingleheim, Breckinridge Pharma, Celgene, Centocor, Inc, Cellceutix, Cipher, Combinatrix, Connetics Corporation, Coria, Dermavant, Dermira, Dow Pharmaceutical Sciences, Inc, Dr Reddy's Lab, Eli Lilly, Galderma, Genentech, Inc, GlaxoSmithKline, PLC, Idera, Leo, Maruho, Merck, Medicis Pharmaceutical Corp., Novartis AG, Promius, PharmaDerm, Pfizer, Serono, Stiefel Laboratories, Inc, Sun Pharma, Taro, UCB, Valeant Pharmaceuticals Intl, and XenoPort. Dr Koo is a speaker and/or advisor for AbbVie, Amgen, Lilly, UCB, Ortho Dermatologics, LEO, Sun Pharma, Janssen, and Epi Pharm. Dr Langley has been an investigator, served on the scientific advisory board, and/or has provided a lecture for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Leo, Lilly, Merck, Novartis, Pfizer, and UCB. Dr Lebwohl is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc; and is a consultant for Aditum Bio, Almirall, AltruBio Inc, AnaptysBio, Arcutis, Inc, Arena Pharmaceuticals, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Brickell Biotech, Boehringer-Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corevitas, Dermavant Sciences, Dr Reddy's Laboratories, Evelo Biosciences, Evommune, Inc, Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica. Dr Lewitt has received speaking and/or consulting support from AbbVie, Lilly, Janssen, Ortho Dermatologics, UCB, Galderma, Pfizer; received honoraria; and served as an advisor for AbbVie, Janssen, and Dermavant. Dr Liao has received research/grant support from AbbVie, Amgen, Janssen, Leo, Novartis, Trex Bio, Pfizer, and Regeneron. Dr Martin has served as an advisor for Bristol Meyers Squibb, DUSA/SUN, AbbVie, Ortho/Bausch Health, Galderma, Pfizer, LEO, Janssen, Horizon, UCB, Trevi, Almirall, Dermavent, Incyte, and Lilly; has served as a consultant for Bristol Meyers Squibb, DUSA/SUN, AbbVie, Ortho/Bausch Health, Galderma, Pfizer, LEO, UCB, Trevi, Almirall, Lilly, Arcutis, and Dermavant; and has received speaking support from UCB, Almirall, LEO, Incyte, Dermavant, and Bristol Meyers Squibb. Dr Orbai is a consultant and/or advisor for Janssen, Novartis, and UCB; and receives research support from AbbVie, Amgen, and Celgene. Dr Reddy has served as a consultant for Novartis, AbbVie, Janssen, and UCB; and has received grant support from Pfizer. Ms Richardson has served as an advisor for and received honoraria from Boehringer Engelheim and Lilly. Dr Ritchlin is a consultant and/or speaker for Novartis, Lilly, AbbVie, Janssen, UCB, and Pfizer. Dr Schwartzman has received speaking support from AbbVie, Janssen, Lilly, Pfizer, Novartis, and UCB; served as a consultant for Abbvie, Janssen, Lilly, Myriad, Novartis, Regeneron, Sanofi, UCB, Stelexis, Jubilant, and Teijin; is a board member of the National Psoriasis Foundation; and served as an advisor for Myriad. Dr Siegel has served as an advisor, speaker, and/or consultant for Abbvie, UCB, Lilly, Horizon, and BMS. Dr Van Voorhees has served as a research investigator and/or scientific advisor for Lilly, AbbVie, UCB, Bristol Meyers Squibb, Amgen, Boehringer Ingelheim, Novartis, and Merck. Dr Wallace serves as an investigator for Pfizer and Target RWE. Dr Weinberg is a research investigator, consultant, and/or speaker for Novartis, Lilly, Amgen, AbbVie, Sun, Janssen, and BMS. Dr Winthrop is a consultant for Pfizer, AbbVie, Union Chimique Belge (UCB), Eli Lilly & Company, Galapagos, GlaxoSmithKline (GSK), Roche, Gilead, Bristol Myers Squibb (BMS), Regeneron, Sanofi, AstraZeneca, and Novartis; and receives research funding from BMS and Pfizer. Dr Yamauchi serves as a research investigator, consultant, and speaker for Abbvie, Amgen, BMS, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, UCB. Dr Armstrong has served as a research investigator, scientific advisor, and/or speaker to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, and Pfizer., (Copyright © 2024. Published by Elsevier Inc.)

Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family of intracellular signalling molecules. By participating in signalling pathways downstream of type I interferons, IL-12, IL-23 and IL-10, TYK2 elicits a distinct set of immune events to JAK1, JAK2 and JAK3. TYK2 polymorphisms have been associated with susceptibility to various rheumatic diseases including systemic lupus erythematosus and dermatomyositis. In vitro and animal studies substantiate these findings, highlighting a role for TYK2 in diseases currently managed by antagonists of cytokines that signal through TYK2. Various inhibitors of TYK2 have now been studied in human disease, and one of these inhibitors, deucravacitinib, has now been approved for the treatment of psoriasis. Phase II trials of deucravacitinib have also reported positive results in the treatment of psoriatic arthritis and systemic lupus erythematosus, with a preliminary safety profile that seems to differ from that of the JAK1, JAK2 and JAK3 inhibitors. Two other inhibitors of TYK2, brepocitinib and ropsacitinib, are also in earlier stages of clinical trials. Overall, TYK2 inhibitors hold promise for the treatment of a distinct spectrum of autoimmune diseases and could potentially have a safety profile that differs from other JAK inhibitors., (© 2024. Springer Nature Limited.)

Objectives: Genome-wide association studies (GWAS) have identified loci associated with estimated glomerular filtration rate (eGFR). Few LN risk loci have been identified to date. We tested the association of SLE and eGFR polygenic risk scores (PRS) with repeated eGFR measures from children and adults with SLE., Methods: Patients from two tertiary care lupus clinics that met ≥4 ACR and/or SLICC criteria for SLE were genotyped on the Illumina MEGA or Omni1-Quad arrays. PRSs were calculated for SLE and eGFR, using published weighted GWA-significant alleles. eGFR was calculated using the CKD-EPI and Schwartz equations. We tested the effect of eGFR- and SLE-PRSs on eGFR mean and variance, adjusting for age at diagnosis, sex, ancestry, follow-up time, and clinical event flags., Results: We included 1158 SLE patients (37% biopsy-confirmed LN) with 36 733 eGFR measures over a median of 7.6 years (IQR: 3.9-15.3). LN was associated with lower within-person mean eGFR [LN: 93.8 (s.d. 26.4) vs non-LN: 101.6 (s.d. 17.7) mL/min per 1.73 m2; P < 0.0001] and higher variance [LN median: 157.0 (IQR: 89.5, 268.9) vs non-LN median: 84.9 (IQR: 46.9, 138.2) (mL/min per 1.73 m2)2; P < 0.0001]. Increasing SLE-PRSs were associated with lower mean eGFR and greater variance, while increasing eGFR-PRS was associated with increased eGFR mean and variance., Conclusion: We observed significant associations between SLE and eGFR PRSs and repeated eGFR measurements, in a large cohort of children and adults with SLE. Longitudinal eGFR may serve as a powerful alternative outcome to LN categories for discovery of LN risk loci., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The goal of this study was to identify protein and transcriptional biomarkers and pathways associated with baseline disease state, the effect of filgotinib (FIL) treatment on these biomarkers, and to investigate the mechanism of action of FIL on clinical improvement in patients with active psoriatic arthritis (PsA)., Methods: The phase II EQUATOR (NCT03101670) trial evaluated the efficacy of FIL, a Janus kinase 1-preferential inhibitor, in patients with PsA. Peripheral protein and gene expression levels in association with clinical state at baseline and post-treatment were assessed in 121 patients using linear mixed effects models for repeated measures analyses. Mediation analysis and structural equation modelling (SEM) were performed to investigate the mechanism of action of FIL at week 4 on downstream clinical improvement at week 16., Results: Baseline analyses showed that markers of inflammation were significantly associated with multiple PsA clinical metrics, except for Psoriasis Area and Severity Index (PASI), which corresponded to Th17 markers. FIL treatment resulted in sustained transcriptional inhibition of immune genes and pathways, a sustained increase in B-cell fraction and mature B-cells in circulation, and a transient effect on other cell fractions. Mediation analysis revealed that changes in B cells, systemic inflammatory cytokines and neutrophils at week 4 were associated with changes in clinical metrics at week 16. SEM suggested that FIL improved PASI through reduction of IL-23 p19 and IL-12 p40 proteins., Conclusions: Our results revealed that FIL treatment rapidly downregulates inflammatory and immune pathways associated with PsA disease activity corresponding to clinical improvement in PsA., Trial Registration Number: NCT03101670., Competing Interests: Competing interests: VAM, KLI, YL, LV, OKY, JL, MT and AH are/were employees of Gilead Sciences and owners of company stock. MT and LV were affiliated with Gilead Sciences at the time of the trial. MT is currently affiliated with Amgen, and LV is currently affiliated with Novo Nordisk. The trial was designed and conducted by the sponsor (Gilead Sciences and Galapagos) in collaboration with the principal investigators and in accordance with the protocol and amendments. The sponsor collected data, monitored trial conduct and performed the statistical analyses. VC has received research grants from AbbVie, Amgen and Eli Lilly and has received honoraria for advisory board member roles from AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. His spouse is an employee of AstraZeneca. He is supported by a Pfizer Chair in Rheumatology salary award. DG received grants and/or consulting fees from Abbvie, Amgen, BMS, Gilead, Galapagos, Eli Lilly, Janssen, Novartis, Pfizer and UCB., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Psoriatic arthritis (PsA) is a chronic inflammatory condition predominantly affecting the peripheral joints. However, some patients with PsA can experience axial involvement which is manifested with back pain and associated with increased burden of illness., Objectives: The aim of this post hoc analysis was to determine the efficacy of ixekizumab (IXE) up to 52 weeks in reducing axial symptoms in PsA patients, presenting with axial manifestations., Design: This was a post hoc analysis of two pooled phase III clinical trials., Methods: Patients with axial manifestations, from two placebo-controlled, randomized, double-blind, phase III trials (SPIRIT-P1 and SPIRIT-P2), were defined as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 (Q2; back pain)] total score ⩾4 and average of BASDAI Q5 + Q6 (morning stiffness) ⩾4 at baseline. For this post hoc analysis, the efficacy of IXE was evaluated at weeks 16, 24, and 52 using separate BASDAI questions (including back pain and morning stiffness), total BASDAI and modified BASDAI (mBASDAI; without Q3), Ankylosing Spondylitis Disease Activity Score (ASDAS), and 50% improvement in BASDAI (BASDAI50) response. Treatment comparisons were performed using logistic regression and analysis of covariance model for categorical and continuous end points, respectively., Results: In the post hoc analysis among PsA patients with axial manifestations at baseline ( N  = 313), improvements in back pain and morning stiffness at weeks 16 and 24 were significantly greater in patients receiving IXE versus placebo (both p  < 0.001). Improvements in BASDAI individual scores and total scores, mBASDAI, and ASDAS were significantly greater in patients receiving IXE compared with placebo. Similarly, significantly more IXE-treated patients achieved BASDAI50 at weeks 16 and 24 versus placebo. The effect of IXE was sustained at week 52. Similar effects were observed in sensitivity analyses subgroups., Conclusion: IXE is effective in improving axial symptoms in patients with active PsA presenting with axial manifestations., Competing Interests: AD reports consulting fees from and has participated on advisory boards from AbbVie, Bristol Myers Squibb, Eli Lilly and Company, Janssen, Moonlake, Novartis, Pfizer, and UCB, and has received research grant from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Galvani, Janssen, Novartis, Pfizer and UCB. DG reports grants or contracts from Abbvie, Amgen, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB, consulting fees from Abbvie, Amgen, BMS, Galapagos, Gilead, Eli Lilly and Company, Janssen, Novartis, Pfizer, and UCB, and serves on the steering or executive committees for GRAPPA and SPARCC. PN reports consulting fees for and honoraria for lectures on behalf of Eli Lilly and Company, DP reports grants or contracts from AbbVie, Eli Lilly and Company, MSD, Novartis, and Pfizer, consulting fees from AbbVie, Biocad, Eli Lilly and Company, Galapagos, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis, and UCB, speaking fees from AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB, RB, DMS, SYP, and SLL are employees and shareholders of Eli Lilly and Company. The Editor-in-Chief of Therapeutic Advances in Musculoskeletal Disease is an author of this paper, therefore, the peer review process was managed by alternative members of the Board and the submitting Editor was not involved in the decision-making process., (© The Author(s), 2023.)

Objectives: We evaluated the association of lupus nephritis (LN) and adverse pregnancy outcomes in prospective cohorts of pregnant women with SLE (systemic lupus erythematosus)., Methods: We conducted a patient-level pooled analysis of data from three cohorts of pregnant women with SLE. Pooled logistic regression models were used to evaluate the association of LN and adverse pregnancy outcomes. Odds ratios and 95% confidence intervals were calculated using a fixed effect model by enrolling cohort., Results: The pooled cohort included 393 women who received care at clinics in the United States and Canada from 1995 to 2015. There were 144 (37%) women with a history of LN. Compared to women without LN, those with LN had higher odds of fetal loss (OR: 1.90; 95% CI: 1.01, 3.56) and preeclampsia (OR: 2.04; 95% CI: 1.01, 4.13). Among the 31 women with active nephritis (defined as urine protein ≥ 0.5 g/24 h) there was a higher odds of poor pregnancy outcome (OR: 3.08; 95% CI: 1.31, 7.23) and fetal loss (OR: 6.29; 95% CI: 2.52, 15.70) compared to women without LN., Conclusions: In this pooled cohort of women with SLE, a history of LN was associated with fetal loss and preeclampsia. Active nephritis was associated with poor pregnancy outcome and fetal loss.

An increasing amount of evidence has emerged suggesting that hidradenitis suppurativa (HS) is associated with inflammatory arthritis. This study reviewed the incidence, prevalence, and predictors of inflammatory arthritis in patients with HS. A comprehensive literature search was conducted in CINAHL, Embase, and Medline from inception to February 14, 2020. Articles were included in the review if they provided data on disease epidemiology or predictors of adult or pediatric HS patients with comorbid inflammatory arthritis. There are no validated diagnostic criteria for HS, thus we considered patients as having HS if they had at least one diagnostic code in a hospital or claims database or a diagnosis of HS/inflammatory arthritis in a medical record. The same criteria were used to confirm presence of inflammatory arthritis. We identified an increased incidence of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) in HS patients when compared with estimates in the general population. We identified a relatively high prevalence of RA, spondyloarthritis (SpA), and PsA in HS patients when compared with estimates in the general population. There was evidence to suggest that patients who are younger than 30, male, have severe HS, or are taking infliximab or adalimumab (which may also be confounded by HS disease severity) may be at greater risk for specific subtypes of inflammatory arthritis. However, further data are needed to confirm these associations. The increased incidence and prevalence of inflammatory arthritis within HS patients underscore the need for increased awareness and interdisciplinary partnership within rheumatology and dermatology., (© 2021 the International Society of Dermatology.)

Introduction: Low disease activity (LDA)/remission is the target of treatment in patients with psoriatic arthritis (PsA). We assessed the proportions of patients with PsA receiving upadacitinib who achieved LDA/remission over 1 year., Methods: This was a post hoc analysis of the double-blind, placebo-controlled SELECT-PsA 1 (also adalimumab-controlled) and SELECT-PsA 2 trials. Treatment targets assessed included LDA/remission defined by Disease Activity in Psoriatic Arthritis (≤ 14/ ≤ 4) and Psoriatic Arthritis Disease Activity Scores (≤ 3.2/ ≤ 1.9), as well as minimal disease activity (MDA)/very low disease activity (VLDA) states (5/7 and 7/7 components, respectively, of MDA criteria). Targets were assessed at 24 and 56 weeks. For binary outcomes, non-responder imputation was used for missing data. Data from patients receiving upadacitinib 30 mg was not included in the analysis., Results: Overall, 1386 patients were analyzed. Disease control (i.e., LDA/MDA) was achieved at 24 weeks in upadacitinib 15 mg-treated patients across both studies: LDA/MDA was achieved by 25-48% of patients receiving upadacitinib 15 mg versus 2-16% of patients receiving placebo, and remission/VLDA rates were 7-14% with upadacitinib 15 mg versus 0-4% with placebo. The proportions of patients achieving treatment targets were numerically similar to upadacitinib 15 mg and adalimumab. All responses were sustained at 56 weeks., Conclusions: Remission and LDA are feasible targets with upadacitinib treatment in patients with PsA., Trial Registration: ClinicalTrial.gov identifiers NCT03104400 (SELECT-PsA 1) and NCT03104374 (SELECT-PsA 2)., (© 2022. The Author(s).)

Background: We have previously shown that 15 urinary biomarkers (of 129 tested by Luminex), discriminate between active Lupus Nephritis (ALN) and non-LN patients. The aim of this study was to evaluate the ability of these 15 previously-identified urinary biomarkers to predict treatment responses to conventional therapy, and for the most predictive of these biomarkers to validate their utility to identify ALN patients in an independent prospectively-acquired lupus cohort., Methods: Our study had a 3-stage approach. In stage 1, we used Luminex to examine whether our previously identified urinary biomarkers at the time of the renal flare ( ± 3 months) or 12 ± 3 months after treatment of biopsy-proven ALN could predict treatment responses. In stage 2, a larger prospectively-acquired cross-sectional cohort was used to further validate the utility of the most predictive urinary biomarkers (identified in stage 1) to detect ALN patients. In this 2 nd stage, cut-offs with the best operating characteristics to detect ALN patients were produced for each biomarker and different combinations and/or numbers of elevated biomarkers needed to accurately identify ALN patients were analyzed. In stage 3, we aimed to further corroborate the sensitivity of the cut-offs created in stage 2 to detect ALN patients in a biopsy-proven ALN cohort who had a urine sample collection within 3 months of their biopsy., Results: Twenty-one patients were included in stage 1. Twelve (57.1%), 4 (19.1%), and 5 (23.8%) patients had a complete (CR), partial (PR) and no (NR) remission at 24 ± 3 months, respectively. The percentage decrease following 12 ± 3 months of treatment for Adiponectin, MCP-1, sVCAM-1, PF4, IL-15 and vWF was significantly higher in patients with CR in comparison to those with PR/NR. In stage 2, a total of 247 SLE patients were included, of which 24 (9.7%) had ALN, 79 (31.9%) had LN in remission (RLN) and 144 (58.3%) were non-LN (NLN) patients. Based on the combinations of biomarkers with the best operating characteristics we propose "rule out" and "rule in" ALN criteria. In stage 3, 53 biopsy-proven ALN patients were included, 35 with proliferative LN and 18 with non-proliferative ALN, demonstrating that our "rule in ALN" criteria operate better in detecting active proliferative than non-proliferative classes., Conclusions: Our results provide further evidence to support the role of Adiponectin, MCP-1, sVCAM-1 and PF4 in the detection of proliferative ALN cases. We further show the clinical utility of measuring multiple rather than a single biomarker and we propose novel "rule in" and "rule out" criteria for the detection of proliferative ALN with excellent operating characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Whittall-Garcia, Goliad, Kim, Bonilla, Gladman, Urowitz, Fortin, Atenafu, Touma and Wither.)

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).

Objective: To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic., Study Design: The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted., Results: The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus., Limitations: The evidence behind many guidance statements is variable in quality and/or quantity., Conclusions: These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge., Competing Interests: Conflicts of interest Dr Gelfand has served as a consultant for Bristol Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Janssen Biologics, Novartis Corp, Regeneron, UCB (Data Safety and Monitoring Board), Sanofi, and Pfizer, receiving honoraria; has received research grants (to the Trustees of the University of Pennsylvania) from AbbVie, Janssen, Novartis Corp, Sanofi, Celgene, OrthoDermatologics, and Pfizer; has received payment for continuing medical education work related to psoriasis that was supported indirectly by Eli Lilly and Company and Ortho Dermatologics; is a copatent holder of resiquimod for treatment of cutaneous T-cell lymphoma; and is a deputy editor for the Journal of Investigative Dermatology, receiving honoraria from the Society for Investigative Dermatology. Dr Armstrong has served as a research investigator and/or scientific advisor to Leo, AbbVie, UCB, Incyte, Janssen, Lilly, Novartis, Ortho Dermatologics, Sun, Dermavant, Bristol Myers Squibb, Sanofi, Regeneron, Dermira, and Modmed. Dr Bell is an employee of the National Psoriasis Foundation. Dr Anesi is supported by the Agency for Healthcare Research and Quality (K12HS026372) and has received fees from UpToDate for authoring COVID-19 clinical reference material. Dr Blauvelt has served as a scientific advisor and/or clinical study investigator for AbbVie, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly and Company, Evommune, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Pfizer, Rapt, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB Pharma. Dr Calabrese is a speaker for Sanofi-Regeneron and consultant for AbbVie. Dr Feldman has received research, speaking, and/or consulting support from Galderma, GlaxoSmithKline/Stiefel, Almirall, Alvotech, Leo Pharma, Bristol Myers Squibb, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho Dermatology, AbbVie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, and National Psoriasis Foundation; has consulted for others through Guidepoint Global, Gerson Lehrman, and other consulting organizations; is the founder and majority owner of www.DrScore.com; and is a founder and part owner of Causa Research, a company dedicated to enhancing patients' adherence to treatment. Dr Gladman is a consultant for AbbVie, Amgen, Bristol Myers Squibb, Galapagos, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, and UCB and has received grants from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB. Dr Kircik has served either as an investigator, consultant, or speaker for AbbVie, Almirall, Amgen, Arcutis, Bausch Health Canada, Bristol Myers Squibb, Boehringer Ingelheim, Cellceutix, Celgene, Coherus, Dermavant, Dermira, Eli Lilly, Leo, MC2, Maruho, Novartis, Ortho Dermatologics, Pfizer, Dr Reddy's Laboratories, Sun Pharma, UCB, Taro, and Xenoport. Dr Lebwohl is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Incyte, Janssen Research and Development, Leo Pharmaceuticals, Ortho Dermatologics, Pfizer, and UCB; and is a consultant for Aditum Bio, Allergan, Almirall, Arcutis, Avotres Therapeutics, BirchBioMed, BMD Skincare, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr Reddy's Laboratories, Serono, Theravance, and Verrica. Dr Martin is a consultant for Almirall, Athenex, Bristol Meyers Squibb, Celgene, Eli Lilly, LEO, Ortho Dermatologic, Pfizer, and UCB and a scientific advisor for Almirall, Athenex, Bristol Meyers Squibb, Celgene, Eli Lilly, Janssen, LEO, Ortho Dermatologic, Pfizer, and UCB. Dr Merola is a consultant and/or investigator for Bristol Myers Squibb, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Sun Pharma, Pfizer, and EMD Serono. Dr Scher is a consultant for UCB, Janssen, AbbVie, Pfizer, Novartis, Bristol Myers Squibb, and Sanofi and is supported in part by the Riley Family Foundation and the Beatrice Snyder Foundation. Dr Schwartzman is a speaker for AbbVie, Genentech, Janssen, Lilly, Novartis, Pfizer, and UCB; owns stock in Amgen, Boston Scientific, Gilead, Medtronic, and Pfizer; is a consultant for AbbVie, Myriad, Janssen, Gilead, Lilly, Novartis, and UCB; is a scientific advisory board member for Myriad; and is a board member of the National Psoriasis Foundation. Dr Van Voorhees has been an investigator for Celgene, Lilly, and AbbVie and an advisor/consultant for AbbVie, Allergan, AstraZeneca, Celgene, Dermira, Merck, Novartis, Pfizer, UCB, and Valeant. Dr Syed is supported by a grant from Pfizer. Authors Gondo, Heydon, and Koons are employees of the National Psoriasis Foundation. Dr Ritchlin reports personal fees from AbbVie, Amgen, Janssen, Novartis, UCB, and Boehringer Ingelheim, as well as grants from Amgen, UCB, and AbbVie outside the submitted work. Drs Dommasch, Lo Re, Treat, Ellebrecht, Fenner, Ocon, and Weinstein have no conflicts of interest to declare., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Infection is a leading cause of death in the SLE population. Low immunoglobulin levels might be a potential risk for infection. We aimed to assess whether acquired low levels of any type of immunoglobulin increase the risk of clinically relevant infection in adult patients with SLE., Methods: We compared adult SLE patients who had acquired any low immunoglobulin levels (IgA, IgM or IgG) for 2 years with patients with normal or high levels with respect to clinically relevant infection (defined as infections requiring intravenous or oral antibiotics) in a prospective cohort study. Group balance was achieved using propensity score adjustment, matching and inverse probability weighting. Primary analysis was time to event using Cox-regression modelling adjusting for potential confounders. Sensitivity analyses were conducted to examine several exposure and outcome definitions., Results: Patients with hypogammaglobulinaemia had longer disease duration, more lupus nephritis history, higher proteinuria and more accumulated damage. Low IgA level was associated with increased risk of clinically relevant infection [hazard ratio (HR): 2.24, 95% CI: 1.61, 3.12] while low IgG (HR: 1.15, 95% CI: 0.84, 1.59) or low IgM (HR: 0.95, 95% CI: 0.73, 1.23) was not. Low immunoglobulin recovery in the first year was 2.5% (11), second year 8.2% (36), third year 10.1% (44) and fourth year 18.4% (80), and 60% (263) of acquired hypogammaglobulinaemia recovered over 4 years., Conclusion: The majority of acquired hypogammaglobulinaemia in adult patients with SLE is transient. Only low acquired IgA was associated with increased risk of infection among adult patients with SLE. Whether immunoglobulin replacement provides additional protective effect requires further investigation., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To provide guidance about management of psoriatic disease during the coronavirus disease 2019 (COVID-19) pandemic., Study Design: A task force (TF) of 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care was convened. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation (NPF) staff. Clinical questions relevant to the psoriatic disease community were informed by questions received by the NPF. A Delphi process was conducted., Results: The TF approved 22 guidance statements. The average of the votes was within the category of agreement for all statements. All guidance statements proposed were recommended, 9 with high consensus and 13 with moderate consensus., Limitations: The evidence behind many guidance statements is limited in quality., Conclusion: These statements provide guidance for the management of patients with psoriatic disease on topics ranging from how the disease and its treatments impact COVID-19 risk and outcome, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 and what they should do if they develop COVID-19. The guidance is intended to be a living document that will be updated by the TF as data emerge., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: We previously found that serum levels of chemokine (C-X-C motif) ligand 10 (CXCL10) decreased after the onset of psoriatic arthritis (PsA)., Objectives: We measured CXCL10 levels over time in patients with psoriasis who developed PsA to determine whether the drop in CXCL10 was specific to these patients and further assess its association with PsA development., Methods: Prospectively followed patients with psoriasis without arthritis [cutaneous psoriasis (PsC)] were assessed yearly by rheumatologists for the presence of PsA. Patients with PsC who developed PsA (converters) were matched to those that did not develop PsA (nonconverters) based on psoriasis duration and the interval between follow-up visits. The duration between baseline and the first visit postconversion in converters was used to assign a pseudoconversion date in nonconverters. Linear mixed-effects models were used to model the expression of CXCL10 over time., Results: CXCL10 significantly declined over time in converters prior to PsA development with a significant difference in the trend over time between converters (n = 29) and nonconverters (n = 52; P < 0·001). CXCL10 continued to decline after PsA onset in a subset of converters. There was a significant difference in the trend of CXCL10 levels between converters (n = 24) and nonconverters (n = 16; P = 0·01) preconversion/pseudoconversion. This difference remained postconversion (P = 0·006) and was not different from the preconversion period (P = 0·75)., Conclusions: A large difference in CXCL10 was identified in patients with PsC that are destined to develop PsA over time. This exploratory analysis supports the association of CXCL10 with PsA development in patients with PsC and warrants further study of the predictive ability of this chemokine. What is already known about this topic? Chemokine (C-X-C motif) ligand 10 (CXCL10) is elevated in psoriatic affected tissues and serum and/or plasma. Patients with psoriasis that develop psoriatic arthritis (PsA) have elevated CXCL10 levels at baseline and these levels drop after arthritis onset. What does this study add? By monitoring levels of CXCL10 in serum over multiple visits in patients with psoriasis that develop PsA as well as those that do not develop PsA, an association was identified between CXCL10 and PsA development. What is the translational message? CXCL10 is a strong candidate for use by physicians for the detection of patients with psoriasis that are at risk of developing PsA. Linked Comment: Kirby and Fitzgerald. Br J Dermatol 2020; 183:805-806., (© 2020 British Association of Dermatologists.)

Objective: To investigate the relationship between physical examination (PE) and sonographic features of enthesitis, based on anatomical sites., Methods: The analysis was done using merged raw data of 3 studies on 2298 entheses., Results: Patients with clinical Achilles enthesitis had more abnormalities on ultrasound (US): hypoechogenicity, p < 0.001; thickening, p = 0.001; Doppler signals, p = 0.002; and erosions, p = 0.02. The patellar tendon origin also correlated with PE but distal patellar tendon insertion and plantar aponeurosis were uncoupled from the US., Conclusion: The relationship between clinical and sonographic findings for large entheses is dependent on the anatomical site. For the patellar tendon origin and Achilles entheses, PE is significantly linked to US findings.

Chronic plaque psoriasis and psoriatic arthritis are multifactorial inter-related diseases with strong genetic contributions. Better elucidation of the heritability of psoriatic disease subsets is important for identifying novel genes, risk stratification and potential clinical applications. In this study, we used two mixed-effect modelling methodologies to assess the additive contribution of common single nucleotide polymorphisms from genome-wide association studies to estimate the heritability of cutaneous psoriasis, psoriasis vulgaris and psoriatic arthritis. We found that cutaneous psoriasis and psoriatic arthritis both exhibit considerable heritability, with a greater contribution coming from cutaneous psoriasis.

Objectives: This study assessed the psychometric properties of the fatigue numeric rating scale (NRS) and sought to establish values for clinically meaningful change (responder definition)., Methods: Using disease-specific clinician-reported and patient-reported data from two randomised clinical trials of patients with psoriatic arthritis (PsA), the fatigue NRS was evaluated for test-retest reliability, construct validity and responsiveness. A responder definition was also explored using anchor-based and distribution-based methods., Results: Test-retest reliability analyses supported the reproducibility of the fatigue NRS in patients with PsA (intraclass correlation coefficient=0.829). Mean (SD) values at baseline and week 2 were 5.7 (2.2) and 5.7 (2.4), respectively. Supporting construct validity of the fatigue NRS, moderate-to-large correlations with other assessments measuring similar concepts as measured by Sackett's conventions were demonstrated. Fatigue severity was reduced when the underlying disease activity was improved and reductions remained consistent at week 12 and 24. A 3-point improvement was identified as being optimal for demonstrating a level of clinically meaningful improvement in fatigue NRS after 12-24 weeks of treatment., Conclusions: Fatigue NRS is a valid and responsive patient-reported outcome instrument for use in patients with PsA. The established psychometric properties from this study support the use of fatigue NRS in clinical trials and in routine clinical practice. Robust validation of reliability for use in routine clinical practice in treating patients with active PsA in less active disease states and other more diverse ethnic groups is needed., Competing Interests: Competing interests: DG received research grant support and/or consulting fees from Abbvie, Amgen, BMS, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer and UCB. PN has received grants for research and for clinical trials and honoraria for advice and lectures from AbbVie, Amgen, BMS, Celgene, Eli Lilly and Company, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi and UCB. HG has received fees for speaking and/or consulting from Abbie, Asahi Kasei, Astellas, Chugai, Eisai, Eli Lilly and Company, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Santen, Takeda, and received research funding to Osaka City General Hospital from AbbVie, Chugai, Eisai, Eli Lilly and Company, Janssen, Sanofi and Santen. A-MO received research grant support and/or consulting fees from Celgene, Eli Lilly and Company, Horizon, Janssen, Novartis, Pfizer and UCB. TKK has received fees for speaking and/or consulting from AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly and Company, Epirus, Hospira, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sandoz, and UCB and received research funding to Diakonhjemmet Hospital from AbbVie, BMS, MSD, Pfizer, Roche and UCB. JB and C-YL are full-time employees of and hold stock/stock options in Eli Lilly and Company., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: This study aimed to assess whether subclinical atherosclerosis, as evaluated by carotid ultrasound, could predict incident cardiovascular events (CVEs) in patients with psoriatic disease (PsD) and determine whether incorporation of imaging data could improve CV risk prediction by the Framingham Risk Score (FRS)., Methods: In this cohort analysis, patients with PsD underwent ultrasound assessment of the carotid arteries at baseline. The extent of atherosclerosis was assessed using carotid intima-media thickness (CIMT) and total plaque area (TPA). Incident CVEs (new or recurrent) that occurred following the ultrasound assessment were identified. The association between measures of carotid atherosclerosis and the risk of developing an incident CVE was evaluated using Cox proportional hazards models, with adjustment for the FRS., Results: In total, 559 patients with PsD were assessed, of whom 23 had incident CVEs ascertained. The calculated rate of developing a first CVE during the study period was 1.11 events per 100 patient-years (95% confidence interval [95% CI] 0.74-1.67). When analyzed separately in Cox proportional hazards models that were controlled for the FRS, the TPA (hazard ratio [HR] 3.74, 95% CI 1.55-8.85; P = 0.003), mean CIMT (HR 1.21, 95% CI 1.03-1.42; P = 0.02), maximal CIMT (HR 1.11, 95% CI 1.01-1.22; P = 0.03), and high TPA category (HR 3.25, 95% CI 1.18-8.95; P = 0.02) were each predictive of incident CVEs in patients with PsD., Conclusion: The burden of carotid atherosclerosis is associated with an increased risk of developing future CVEs. Combining vascular imaging data with information on traditional CV risk factors could improve the accuracy of CV risk stratification in patients with PsD., (© 2019, American College of Rheumatology.)

Psoriasis is a multisystemic, inflammatory skin condition that can affect many areas of the body, but most commonly the extensor surfaces of the elbows and knees, and sometimes the intergluteal and umbilical area. It has a prevalence of 2-4% in western adults, and 20--30% of psoriasis patients will develop psoriatic arthritis (PsA). PsA is an inflammatory musculoskeletal disease associated with cutaneous psoriasis. It affects men and women almost equally with a peak age at onset of 40 and 50 years. It is a diverse disease that affects multiple organ systems includes peripheral and axial joints, entheses, skin, and nails. PsA is associated with comorbidities such as osteoporosis, uveitis, subclinical bowel inflammation, and cardiovascular disease. Given this heterogeneity, its diagnosis has been difficult. Here we present an updated review of its classification criteria CASPAR (classification criteria for PsA), use of screening tools to aid in early diagnosis, recent findings on pathogenesis, and new therapeutic approaches including new biologic medications., Competing Interests: Competing interests: DG has received consulting fees and/or grant support from Abbvie, Amgen, Bristol-Myers Squibb (BMS), Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer, and Union Chimique Belge (UCB). VOD has no competing interests to disclose.No competing interests were disclosed.No competing interests were disclosed., (Copyright: © 2019 Ocampo D V and Gladman D.)

Objective: To comprehensively assess evidence on the measurement properties of the minimal disease activity (MDA) criteria, a composite measure of the state of disease activity in psoriatic arthritis (PsA)., Methods: A targeted literature review was conducted to identify studies that informed the validity and/or ability of the MDA to detect change among patients known to have experienced a change in clinical status. The search was conducted using MEDLINE and Embase databases (published as of October 2017). Pertinent articles provided by investigators and identified from select conference proceedings were also evaluated., Results: A total of 20 publications met the inclusion criteria. The MDA criteria were consistently associated with other indicators of disease activity/severity. The ability of the MDA criteria to detect change was supported in randomised controlled trials (n=10), with a greater percentage of patients randomised to active treatments achieving MDA relative to patients in comparator arms. Long-term observational studies (n=2) provided additional support for the ability of the MDA to detect within-subject change in the real-world settings., Conclusion: Evidence supports the MDA as a valid measure of disease activity in PsA that can detect between-group and within-subject change. The MDA is a comprehensive measure and clinically meaningful endpoint to assess the impact of interventions on PsA disease activity., Competing Interests: Competing interests: LCC has received research funding and/or honoraria from AbbVie, Amgen, BMS, Celgene, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Prothena, Sun Pharma, and UCB. LCC is funded by a National Institute for Health Research Clinician Scientist award. The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). VS consults for Amgen, AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, GSK, Janssen, Kezar, Lilly, Merck, Novartis, Pfizer, Samsung, Sandoz, Sanofi, and UCB. HW was an Evidera employee during study conduct and Evidera received research funding for the project from Amgen. HW is currently an employee of Boehringer Ingelheim. DR is employed by Evidera which received research support from Amgen for this project and received research support from Pfizer. DR owns stock in AbbVie, Pfizer, and Amgen. BS, AS and JBC are employees of Amgen and are Amgen stock owners. DG received grant support and/or consulting fees from AbbVie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB. PJM has received research funding, consulting or speaker honoraria from AbbVie, Amgen, BMS, Celgene, Galapagos, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Prothena, Sun Pharma and UCB., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Assessment of spinal lateral flexion (SLF) is important in spondyloarthritis (SpA). The INSPIRE method of measuring SLF requires one set of measurements, is faster, feasible, and correlates with the mSASSS in ankylosing spondylitis. The present study aimed to compare the INSPIRE to Domjan method in PsA patients and correlate with radiographic changes., Methods: Patients were selected from a cohort followed in a PsA clinic. Patients satisfying CASPAR criteria and having axial disease were identified. Clinical features were recorded. Examination included full spinal clinimetrics including measurement of INSPIRE and Domjan methods. Spine radiographs were scored for mSASSS by two assessors. Pearson correlation was used to correlate the values of spinal mobility measures and radiographic scores., Results: Two hundred twenty-nine patients were included in the study. The mean age at study entry was 51 years (16-83) and mean disease duration was 14 years (0.1-49). Forty and 47% of patients had radiographic evidence of unilateral or bilateral sacroiliitis. The mean modified Schober was 4.5 (1-8 cm), SLF-Domjan 16.5 (3.5-40 cm), SLF-INSPIRE 31.5 (8-60 cm), and mSASSS score 4(0-48). Correlation (95% CI) between INSPIRE and Domjan method was 0.87 (0.82, 0.90), between INSPIRE, Domjan method, and mSASSS were - 0.36 (- 0.50, - 0.20) and - 0.34 (- 0.49, - 0.18) respectively. All correlations were significant. Comparable correlations were obtained with comparisons made in patients of PsA with axial disease only., Conclusion: Both INSPIRE and Domjan methods correlate well as measures of SLF in PsA and correlate with radiographic damage. Therefore, the simpler INSPIRE method may be used to measure SLF in PsA.

Aims: To evaluate disease activity of late onset psoriatic arthritis (LoPsA) patients at presentation, during follow-up, and after 5years of follow-up, compared to young onset PsA patients (YoPsA)., Methods: The study included patients with PsA followed prospectively within 2years from diagnosis. Patients were divided into two groups: (1) LoPsA - defined as disease onset ≥ 50 years, (2) YoPsA - defined as disease onset < 50 years. Descriptive statistics are provided and multivariable logistic regression models were developed to compare these groups., Results: Five hundred and sixty-six patients were included at presentation. Regression analysis showed that the LoPsA group at presentation was characterized by: less males (OR 0.4, p = 0.001), less HLA-C*06 (OR 0.3, p = 0.005), longer psoriasis duration (OR 1.04, p = 0.0005), higher BMI (OR 1.1, p = 0.005) and higher modified Steinbrocker score (mSS) (OR 1.1, p = 0.005). Regression analysis adjusted for gender, BMI, psoriasis duration, HLA and treatments after 5years of follow-up revealed a trend toward higher adjusted mean active joint count (OR 7.98, p = 0.052) and higher mean mSS score (OR 13.39, p = 0.007) in the LoSpA group compared to the YoPsA group. During 5years of follow-up, the YoPsA patients were treated with more NSAIDs (96% vs. 88%, p = 0.04), while there were no significant differences in the DMARDs and biologic drugs., Conclusion: The LoPsA patients at presentation are characterized by female predominance, higher BMI, more damage and less HLA-C*06. After 5years of follow-up the LoPsA patients have worse prognosis manifested by a trend toward higher disease activity burden and significantly more damage., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: This analysis explored the association of treatment adherence with beliefs about medication, patient demographic and disease characteristics and medication types in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) to develop adherence prediction models., Methods: The population was a subset from ALIGN, a multicountry, cross-sectional, self-administered survey study in adult patients (n=7328) with six immune-mediated inflammatory diseases who were routinely receiving systemic therapy. Instruments included Beliefs about Medicines Questionnaire (BMQ) and 4-item Morisky Medication Adherence Scale (MMAS-4 © ), which was used to define adherence., Results: A total of 3390 rheumatological patients were analysed (RA, n=1943; PsA, n=635; AS, n=812). Based on the strongest significant associations, the adherence prediction models included type of treatment, age, race (RA and AS) or disease duration (PsA) and medication beliefs (RA and PsA, BMQ-General Harm score; AS, BMQ-Specific Concerns score). The models had cross-validated areas under the receiver operating characteristic curve of 0.637 (RA), 0.641 (PsA) and 0.724 (AS). Predicted probabilities of full adherence (MMAS-4 © =4) ranged from 5% to 96%. Adherence was highest for tumour necrosis factor inhibitors versus other treatments, older patients and those with low treatment harm beliefs or concerns. Adherence was higher in white patients with RA and AS and in patients with PsA with duration of disease <9 years., Conclusions: For the first time, simple medication adherence prediction models for patients with RA, PsA and AS are available, which may help identify patients at high risk of non-adherence to systemic therapies., Trial Registration Number: ACTRN12612000977875., Competing Interests: Competing interests: JSS has received grants and personal fees from AbbVie, Lilly, MSD, Pfizer and Roche and personal fees from Amgen, AstraZeneca, Astro, Celgene, GlaxoSmithKline, Janssen, MedImmune, Novartis, Samsung and UCB. DG has received grant/research support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene Corporation, Janssen, Pfizer Inc, Novartis and UCB. HPM has received research grants and consulting fees from AbbVie. PJM has received research grants, consulting fees and/or speaker fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, SUN and UCB. JS has received research funds, consulting fees and/or speaker fees from AbbVie, Janssen, Lilly, Novartis, Merck, Pfizer, Roche, Sun Pharma and UCB. MH is an employee of AbbVie and may own AbbVie stock/stock options. PN is a former employee of AbbVie and may own AbbVie stock/stock options. JW has performed work that was paid for by AbbVie and Atlantis Healthcare, either directly or indirectly through an intermediary.

Background: Disease activity in systemic lupus erythematosus follows three different courses: long quiescent, relapsing remitting and persistently active. However, the patterns of disease course since diagnosis are not known. This study aimed to assess the prevalence and characteristics of such patterns over 10 years., Patients and Methods: The inception cohort of the Toronto Lupus Clinic (≥10 year follow up, between visit interval ≤18 months) was investigated. Prolonged remission was defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 = 0 achieved within 5 years of enrolment and maintained for ≥10 years. The relapsing-remitting pattern was defined based on ≥2 remission periods (clinical Systemic Lupus Erythematosus Disease Activity Index 2000 = 0 for two consecutive visits). Patients with no remission were categorized as persistently active. Groups were compared for baseline characteristics, cumulative damage, flare rate, mortality and certain co-morbidities., Results: Of 267 patients, 27 (10.1%) achieved prolonged remission, 180 (67.4%) relapsing-remitting and 25 (9.4%) persistently active. In total, 35 (13.1%) had only one remission period (hybrid). At enrollment, there were no differences regarding clinical and immunological variables. At 10 years, persistently active patients had accumulated significantly more damage than the prolonged remission and relapsing-remitting patients. Being of Black race and higher adjusted mean Systemic Lupus Erythematosus Disease Activity Index 2000 over the first 2 years were associated with a more severe disease course. Relapsing-remitting and persistently active patients had an increased flare rate and accrued more osteoporosis, osteonecrosis and cardiovascular events., Conclusions: Approximately 70% of systemic lupus erythematosus patients followed a relapsing-remitting course, whereas 10% displayed prolonged remission and another 10% a persistently active course. Early response to treatment was associated with a less severe course and better prognosis.

Background: Secukinumab has demonstrated sustained improvement in the signs and symptoms of psoriatic arthritis (PsA) over 2 years in the FUTURE 2 study (NCT01752634). This post hoc analysis assessed the ability of secukinumab to achieve Psoriatic Arthritis Disease Activity Score (PASDAS)-based remission or low disease activity (LDA) through 2 years among patients with PsA in the FUTURE 2 study., Methods: PASDAS (cut-off scores: remission ≤ 1.9; LDA > 1.9 and < 3.2; Moderate Disease Activity ≥ 3.2 and < 5.4; and high disease activity [HDA] ≥ 5.4) was assessed in the overall population (tumour necrosis factor inhibitor [TNFi]-naïve and TNFi-experienced), in patients stratified by prior TNFi use and by disease duration at weeks 16, 52 and 104. The impact of secukinumab on individual PASDAS core components and on the relationship between PASDAS states and patient-reported outcomes (PROs), including physical function, health-related quality of life (HRQoL) and work productivity, were also assessed. Data for the approved doses of secukinumab (300 and 150 mg) are reported. PASDAS scores and core components were reported as observed, and PROs were analysed using mixed models for repeated measures., Results: In the overall population, PASDAS remission and LDA were achieved in 15.6% and 22.9%, respectively, of patients treated with secukinumab 300 mg and in 15.2% and 19.2%, respectively, in the secukinumab 150 mg group versus 2.3% and 13.8%, respectively, with placebo at week 16. In the TNFi-naïve group, a higher proportion of patients achieved remission + LDA at week 16 with secukinumab 300 and 150 mg (46.2% and 42.9%, respectively) versus placebo (17.5%), with corresponding responses in TNFi-experienced patients being 22.6% and 19.4% versus 13.3%. Remission/LDA responses with secukinumab were sustained through 2 years. Patients achieving remission/LDA reported greater improvements in PROs than patients in HDA through 2 years., Conclusions: Secukinumab-treated patients achieved higher PASDAS-defined remissions or LDA compared with placebo at week 16, which were sustained through 2 years. Remission/LDA was achieved by both TNFi-naïve and TNFi-experienced patients treated with secukinumab, with higher rates in TNFi-naïve patients. Secukinumab-treated patients achieving remission/LDA reported significantly greater improvements in PROs, including physical function and different dimensions of health-related quality of life and work, than patients in HDA., Trial Registration: ClinicalTrials.gov, NCT01752634 . Registered on December 19, 2012. EUDRACT, 2012-004439-22 . Registered on December 12, 2012.

Objectives: Patients with psoriatic arthritis (PsA) experience substantial physical impairment. This is commonly assessed using the patient-reported Health Assessment Questionnaire-Disability Index (HAQ-DI), which was originally developed in rheumatoid arthritis. The purpose of this review is to examine the value and challenges of using the HAQ-DI in patients with PsA, and to discuss alternative measures of functional impairment in this condition., Methods: A literature search was performed in the MEDLINE, BIOSIS Previews, Embase, Derwent Drug File, and SciSearch databases using relevant terms and key words. Additional references from personal libraries were identified by the authors., Results: Although validated in PsA, the HAQ-DI has limitations, including marked floor effects, lack of responsiveness to treatment effects in later disease stages, and underestimation of physical impairment in patients whose symptoms are predominantly skin related. Nonetheless, it has been widely used in clinical trials of PsA treatment and is generally responsive to change with effective therapy, discriminating between active and placebo treatments. Other generic or arthritis-specific patient-reported questionnaires with a focus on physical impairment include the Medical Outcomes Study Short Form-36 Health Survey, the EuroQol-5D, the Arthritis Impact Measurement Scales, and the Routine Assessment of Patient Index Data 3. There are currently no PsA-specific instruments to assess physical function, but health-related quality-of-life questionnaires with elements related to functional impairment include the PsA Quality of Life questionnaire, the PsA Impact of Disease questionnaire, and VITACORA-19. As the available measures of physical impairment may not reflect the impact of all aspects of PsA on a patient, additional health-related quality-of-life instruments, such as the Dermatology Life Quality Index, may be used in parallel to obtain a more complete picture of the disease burden., Conclusions: The HAQ-DI is a valuable assessment tool that clinicians should continue to use in clinical trials and practice. Because instruments to specifically assess physical function in patients with PsA are currently lacking, clinicians should consider using a combination of instruments to conduct the most thorough evaluation possible., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Severe brady-arrhythmias, requiring a permanent pacemaker (PPM), have been sparsely reported in systemic lupus erythematosus (SLE). The aim of this study was to describe the characteristics of such arrhythmias in a defined lupus cohort. Patients and methods The database of the Toronto Lupus Clinic ( n = 1366) was searched for patients who received a PPM. Demographic, clinical, immunological and therapeutic variables along with electrocardiographic (ECG) and echocardiographic findings (based on the last available test prior to PPM) were analyzed. Patients with a PPM (cases) were compared with age-, sex- and disease duration-matched patients without a PPM (controls). Analysis was performed with SAS 9.0; p < 0.05 was considered significant. Results Eighteen patients were identified, 13 (0.95%) with complete atrioventricular block and 5 (0.37%) with sick sinus syndrome. Disease duration at PPM implantation was 22 ± 12 years. Compared to controls, cases had more frequently coronary artery disease, hypertension, dyslipidemia and longer antimalarial (AM) treatment duration. The prevalence of first-degree atrioventricular block, right bundle branch block, left anterior fascicular block and septal hypertrophy was also higher. AM treatment was significantly associated with brady-arrhythmias (OR = 1.128, 95% CI = 1.003-1.267, p = 0.044). Nine patients had prior heart disease and one received a PPM two years after renal transplantation. Eight patients did not have any potential risk factors; prolonged AM therapy (mean 22 years) might have been the cause. Conclusions Apart from known causes, prolonged AM treatment may be associated with severe brady-arrhythmias in SLE. Certain ECG and echocardiographic characteristics may represent indicators of an ongoing damage in the conduction system.

Background Lupus myocarditis (LM) is reported in 3-9% of patients with systemic lupus erythematosus (SLE) but limited evidence exists regarding optimal treatment and prognosis. This study aims to describe LM in a defined lupus cohort as compared with the existing literature. Patients and methods Patients with LM were identified from the University of Toronto Lupus Clinic database. Diagnosis was based on clinical manifestations and electrocardiographic, imaging, and biochemical criteria. Demographic, clinical, diagnostic and therapeutic variables and outcomes were collected in a standardized data retrieval form. A literature review was performed to identify cohort studies reporting on LM treatment and outcome. A comparative analysis was conducted between our patients and the combined cohort of the existing studies. Results Thirty patients were diagnosed with LM (prevalence 1.6%) and compared with a cumulative cohort of 117 patients from five distinct studies. No significant differences were found regarding the age at diagnosis (32.6 ± 13.4 years) and SLE duration (2.5 years median). Concomitant lupus activity from other organ systems was observed in 97% of the patients. Chest pain was more frequently reported in our cohort whereas dyspnea was more prominent in the other studies. Diagnostic criteria were similar across studies. Therapeutic approach was comparable and consisted of glucocorticosteroids (96.6%) and immunosuppressives (70%). Mortality was approximately 20% whereas another 20% of the patients achieved partial and 60% complete recovery. Conclusions LM usually occurs early in the disease course and in the context of generalized lupus activity. Despite aggressive therapy, approximately 40% of the patients died or had residual heart damage.

Spondyloarthritis (SpA) represents a group of common diseases that share a number of characteristic clinical manifestations including peripheral arthritis, spondylitis, enthesitis, and dactylitis. Additionally, they can often be associated with extra-articular manifestations including psoriasis, anterior uveitis, and inflammatory bowel disease. The two most widely studied clinical phenotypes are ankylosing spondylitis and psoriatic arthritis. Although a number of biologic agents have been shown to be highly effective in treating these conditions, rheumatologists must generally initiate therapy with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) such as methotrexate and sulfasalazine. The use of these medications stems from our experience in rheumatoid arthritis, and there is a paucity of convincing clinical data supporting their use in SpA. More recently, new targeted synthetic DMARDs have become available and are a welcome addition to the management of these conditions. Through this review, we hope to highlight the evidence behind available treatment options on the various domains of these diseases including synovitis, enthesitis, dactylitis, and spondylitis. We also discuss the available evidence regarding co-medication of csDMARDs with biologic agents., (Copyright © 2018. Published by Elsevier Ltd.)

Ankylosing spondylitis (AS) was first identified in the late 17th century. 250 years later, inflammatory spine disease was recognized to be one of the patterns of psoriatic arthritis (PsA). Isolated spondylitis is rare among patients with PsA, occurring in less than 5% of patients; however, many patients with PsA have axial disease that is concurrent with peripheral arthritis. At the other end of the spondyloarthritis spectrum, psoriasis is observed in 10% of patients with AS. Although axial involvement in PsA can be indistinguishable from axial disease in AS, it can also differ in several respects, raising the question of whether axial PsA and AS (with or without psoriasis) are different clinical presentations of the same disease, or whether they are separate diseases that have overlapping features. In this Review, the clinical presentation, metrology, radiographic characteristics, genetic factors, treatment options and axial prognosis of the two diseases are addressed. The aim of this Review is to capture all available comparisons made to date, to highlight the similarities and differences between AS and axial PsA and to propose a research agenda.

Objective: Enthesitis is an important pathophysiologic component of psoriatic arthritis (PsA). HLA genes are implicated in the pathogenesis of PsA. Little is known about the relationship between HLA genetic susceptibility markers and enthesitis in PsA patients. Our aim was to examine the association between HLA genetic susceptibility markers and sonographic enthesitis in PsA., Methods: A cross-sectional analysis was conducted in patients with PsA. Sonographic enthesitis was assessed according to the Madrid Sonography Enthesitis Index scoring system. HLA genotyping was performed using sequence-specific oligonucleotide probes. The association between 6 HLA susceptibility markers of PsA and the severity of sonographic enthesitis was assessed using multivariate regression models adjusted for age, sex, body mass index, and disease duration., Results: Two hundred twenty-five patients were included, 57.8% of whom were men. The mean ± SD age was 56.1 ± 12.7 years, and the mean ± SD PsA duration was 16.9 ± 12.3 years. In the multivariate regression model, HLA-B*27 was associated with a higher enthesitis score (β = 4.24 [95% confidence interval {95% CI} 0.02, 8.46]), and the interaction between HLA-B*27 and PsA duration was statistically significant, showing an increasing effect of HLA-B*27 with longer PsA duration (β = 4.62 [95% CI 1.38, 7.86])., Conclusion: HLA-B*27 is associated with more severe sonographic enthesitis in PsA, particularly in patients with longer disease duration. This finding highlights the possible role of genetic variants in predisposing to PsA subphenotypes., (© 2018, American College of Rheumatology.)

Background Antimalarials (AMs) are widely used in the treatment of connective tissue diseases. Their main side effect is retinal damage, while heart disease has been described in isolated cases. The aim of this study is to systematically review the existing literature on AM-induced cardiomyopathy (AMIC). Methods The PubMed database was searched for heart biopsy-confirmed AMIC cases. Information on demographics, clinical presentation, concomitant AM-related toxicity, cardiological investigations, treatment and outcome were collected. Descriptive statistics were used. Results Forty-seven cases (42 females) were identified with a mean age at diagnosis 56.4 ± 12.6 and mean AM treatment duration 12.7 ± 8.2 years. Systemic lupus erythematosus ( n = 19) and rheumatoid arthritis ( n = 18) were the most common primary diseases. Clinical presentation was that of congestive heart failure in 77%, while eight patients presented with syncope (17%). Complete atrioventricular block was reported in 17 patients; 24 received a permanent pacemaker (51%). Impaired systolic function was detected in 52.8%, bi-ventricular hypertrophy in 51.4% and restrictive filling pattern of the left ventricle in 18 patients. Cardiac magnetic resonance showed late gadolinium enhancement in seven cases, with a non-vascular pattern in the interventricular septum. Cardiomyocyte vacuolation was reported in all cases; intravacuolar lamellar and curvilinear bodies were observed in 46 (98%) and 42 (89.4%) respectively. Mortality rate was 45% (18/40). Conclusion AMIC is a rare, probably under-recognized, complication of prolonged AM treatment. It presents as a hypertrophic, restrictive cardiomyopathy with or without conduction abnormalities. Early recognition and drug withdrawal are critical with a survival rate of almost 55%.

Objective: To report the efficacy, patient-reported, radiographic and safety outcomes of 4 years' certolizumab pegol (CZP) treatment in patients with psoriatic arthritis (PsA)., Methods: RAPID-PsA (NCT01087788) was double-blind and placebo-controlled to Week 24, dose-blind to Week 48 and open-label (OL) to Week 216. Patients were randomised 1:1:1 to either placebo or CZP 200 mg every 2 weeks (Q2W) or 400 mg every 4 weeks (Q4W) (following 400 mg at Weeks 0/2/4). Patients randomised to CZP continued their assigned dose in the OL period. Patients randomised to placebo were re-randomised to CZP 200 mg Q2W or 400 mg Q4W (post-loading dose) at Week 16 (early escape) or after the double-blind phase. We present observed and imputed data; missing values were imputed using non-responder imputation (NRI) for categorical and last observation carried forward (LOCF) for continuous measures., Results: 409 patients were randomised; 20% (54/273) of Week 0 patients randomised to CZP had prior anti-tumour necrosis factor (TNF) exposure; 67% (183/273) completed 216 weeks. By Week 48, 60.4% of patients achieved Disease Activity Index for Psoriatic Arthritis low disease activity or remission, which was maintained; 66.3% achieved these outcomes at Week 216 (NRI). At Weeks 48 and 216, 39.2% of patients achieved minimal disease activity (NRI). 75% reduction in Psoriasis Area and Severity Index responses were 65% and 52% at Weeks 48 and 216 (NRI). Total resolution rates for enthesitis, dactylitis and nail psoriasis, at 4 years, were 71%, 81% and 65%, respectively (LOCF). Structural damage progression was low over 4 years' treatment. No new safety signals were identified after Week 96., Conclusions: CZP efficacy in treating PsA was maintained over 4 years, in patients both with and without prior anti-TNF exposure, with no new safety signals identified., Competing Interests: Competing interests: DvdH has received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB Pharma and is the director of Imaging Rheumatology bv. AD has received grants or research support from AbbVie, Amgen, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and UCB Pharma and consulting fees from Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. OFG has received grants or research support from AbbVie, Bristol-Myers Squibb, Janssen and Pfizer and consulting fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Pfizer and UCB Pharma and speaker fees from AbbVie, Celgene Janssen, Novartis, Pfizer and UCB Pharma. RF has received grants or research support from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, MSD Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Aventis and UCB Pharma and consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Novartis, Pfizer and Sanofi-Aventis. DG has received grants or research support and consulting fees from Abbott, Amgen, Bristol-Myers Squibb, Celgene, Johnson & Johnson, MSD, Novartis, Pfizer and UCB Pharma. ABG has received consulting fees from Abbott (AbbVie), Aclaris, Actelion, Akros, Allergan, Amgen, Amicus, Astellas, Baxalta, Beiersdorf, Bristol-Myers Squibb, Canfite, Catabasis, Celgene, Centocor (Janssen), Coronado, Crescendo Bioscience, CSL Behring Biotherapies for Life, Dermipsor, Dermira, Eli Lilly, Genentech, GlaxoSmithKline, Incyte, Karyopharm, Kineta One, KPI Therapeutics, Meiji Seika Pharma, Mitsubishi, Novartis, Novo Nordisk, Pfizer, Reddy Labs, Takeda, Tanabe Pharma Development America, TEVA, UCB Pharma, Valeant, Vertex and Xenoport and received grants or research support from Incyte and Janssen. BH, LB, OI-S and LP are employees of UCB Pharma. AT has received grants or research support, consulting fees and speaker fees from Abbvie, Eli Lilly, Janssen, Novartis, Pfizer and UCB Pharma. JW has received grants or research support and consulting fees from UCB Pharma. PJM has received consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer, Sun and UCB Pharma; grants or research support from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer, Sun, UCB Pharma and Zynerba and speaker fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer and UCB Pharma.

Objective: A meeting was convened by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) and Outcome Measures in Rheumatology (OMERACT) to further the development of consensus among physicians and patients regarding composite disease activity measures and targets in psoriatic arthritis (PsA)., Methods: Prior to the meeting, physicians and patients completed surveys on outcome measures. A consensus meeting of 26 rheumatologists, dermatologists, and patient research partners reviewed evidence on composite measures and potential treatment targets plus results of the surveys. The meeting consisted of plenary presentations, breakout sessions, and group discussions. International experts including members of GRAPPA and OMERACT were invited to the meeting, including the developers of all of the measures discussed. After discussions, participants voted on proposals for use, and consensus was established in a second survey., Results: Survey results from 128 health care professionals and 139 patients were analyzed alongside a systematic literature review summarizing evidence. A weighted vote was cast for composite measures. For randomized controlled trials, the most popular measures were the PsA disease activity score (40 votes) and the GRAPPA composite index (28 votes). For clinical practice, the most popular measures were an average of scores on 3 visual analog scales (45 votes) and the disease activity in PsA score (26 votes). After discussion, there was no consensus on a composite measure. The group agreed that several composite measures could be used and that future studies should allow further validation and comparison. The group unanimously agreed that remission should be the ideal target, with minimal disease activity (MDA)/low disease activity as a feasible alternative. The target should include assessment of musculoskeletal disease, skin disease, and health-related quality of life. The group recommended a treatment target of very low disease activity (VLDA) or MDA., Conclusion: Consensus was not reached on a continuous measure of disease activity. In the interim, the group recommended several composites. Consensus was reached on a treatment target of VLDA/MDA. An extensive research agenda was composed and recommends that data on all PsA clinical domains be collected in ongoing studies., (© 2017, American College of Rheumatology.)

Objective The objective of this paper is to identify the relationship between patients with lupus nephritis (LN) who achieve sustained complete renal remission (CR) and renal outcome and survival. Methods From a longitudinal cohort study we identified patients with LN with CR. We compared the outcomes of patients who achieved sustained CR for at least five years (Group A) with those less than five years (Group B). The outcomes were death, SLICC/ACR damage index (SDI), renal flare, end-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) < 50 ml/min, and doubling of serum creatinine. Regression analyses were used to identify predictors of the outcomes. Results A total of 345 patients were identified, 132 patients in Group A and 213 patients in Group B. The duration of CR in Group A was 11.76 ± 7.34 years but only 1.24 ± 1.24 years in Group B ( p < 0.001). Death, increasing renal SDI, renal flare, renal transplantation, ESRD or eGFR < 50 ml/min, and doubling of serum creatinine in Group A were significantly lower than Group B. Multivariable analysis revealed that Group A patients were at a lower risk of death (hazard ratio (HR) = 0.20; 95% confidence interval (CI), 0.07-0.61; p = 0.004), increasing renal SDI (HR = 0.41; 95% CI, 0.21-0.76; p = 0.01), developing ESRD or eGFR < 50 ml/min (HR = 0.27; 95% CI, 0.12-0.61; p = 0.001), and doubling of serum creatinine (HR = 0.29; 95% CI, 0.14-0.61; p = 0.001) compared with Group B. Conclusion Sustained CR for at least five years is a predictor of better prognosis in patients with LN.

Introduction Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE), characterized by decreased lung volumes and extra-pulmonary restriction. The aim of this study was to describe the characteristics of SLS in our lupus cohort with emphasis on prevalence, presentation, treatment and outcomes. Patients and methods Patients attending the Toronto Lupus Clinic since 1980 ( n = 1439) and who had pulmonary function tests (PFTs) performed during follow-up were enrolled ( n = 278). PFT records were reviewed to characterize the pattern of pulmonary disease. SLS definition was based on a restrictive ventilatory defect with normal or slightly reduced corrected diffusing lung capacity for carbon monoxide (DLCO) in the presence of suggestive clinical (dyspnea, chest pain) and radiological (elevated diaphragm) manifestations. Data on clinical symptoms, functional abnormalities, imaging, treatment and outcomes were extracted in a dedicated data retrieval form. Results Twenty-two patients (20 females) were identified with SLS for a prevalence of 1.53%. Their mean age was 29.5 ± 13.3 years at SLE and 35.7 ± 14.6 years at SLS diagnosis. Main clinical manifestations included dyspnea (21/22, 95.5%) and pleuritic chest pain (20/22, 90.9%). PFTs were available in 20 patients; 16 (80%) had decreased maximal inspiratory (MIP) and/or expiratory pressure (MEP). Elevated hemidiaphragm was demonstrated in 12 patients (60%). Treatment with prednisone and/or immunosuppressives led to clinical improvement in 19/20 cases (95%), while spirometrical improvement was observed in 14/16 patients and was mostly partial. Conclusions SLS prevalence in SLE was 1.53%. Treatment with glucocorticosteroids and immunosuppressives was generally effective. However, a chronic restrictive ventilatory defect usually persisted.

Objective There is a decreased risk of breast cancer in systemic lupus erythematosus (SLE) versus the general population; little is known regarding the receptor status of breast cancers in SLE, or treatment. Methods Breast cancer cases occurring after SLE diagnosis were ascertained through linkage with tumor registries. We determined breast cancer positivity for estrogen receptors (ER), progesterone receptors (PR), and/or Human Epidermal Growth Factor Receptor 2 (HER2), as well as cancer treatment. Results We obtained information on ER, PR, and/or HER2 status for 63 SLE patients with breast cancer. Fifty-three had information on ER and/or PR status; 36 of these (69%) were ER positive. Thirty-six of the 63 had information on HER2 status; of these, 26 had complete information on all three receptors. Twenty-one of these 26 (81%) were HER2 negative; seven of 26(27%) were triple negative. All but one patient underwent surgery; 11.5% received both non-tamoxifen chemotherapy and radiotherapy, 16.4% radiotherapy without non-tamoxifen chemotherapy, and 14.7% received non-tamoxifen chemotherapy without radiotherapy. Conclusion ER positivity was similar to historical general population figures, with a trend toward a higher proportion of triple-negative breast cancers in SLE (possibly reflecting the relatively young age of our SLE patients).

Objective Osteonecrosis is a serious comorbidity in patients with systemic lupus erythematosus. The aims of this study were to describe the prevalence of symptomatic osteonecrosis, determine the pattern of joint involvement, identify the outcomes and investigate predictive factors in a large cohort of patients with systemic lupus erythematosus followed prospectively. Methods At the Toronto Lupus Clinic patients have been followed prospectively according to a standard protocol since 1970. Osteonecrosis is recorded if patients are symptomatic and is confirmed by imaging. The site of osteonecrosis is recorded and whether or not surgery was performed. For determination of prevalence, pattern and outcome of osteonecrosis a longitudinal cohort design was performed. For the predictive factors, only patients with incident osteonecrosis were included and were matched for gender, year of entry to clinic (within 5 years), year of birth (within 5 years) and disease duration (within 3 years) with systemic lupus erythematosus patients without osteonecrosis. Results Of 1729 patients with systemic lupus erythematosus registered in the database, 234 (13.5%) developed symptomatic osteonecrosis in 581 sites. Hips and knees were most commonly affected and 47% of the patients had multiple sites involved. More than half of the joints involved at first occurrence of osteonecrosis had surgery. Univariate analysis identified black race, damage, elevated cholesterol and glucocorticosteroids as predictive factors, but glucocorticosteroids remained as the primary predictor for the development of osteonecrosis on multivariable analysis. Conclusion Despite advancements in the assessment and treatment of systemic lupus erythematosus, symptomatic osteonecrosis continues to be a significant comorbidity. Strategies to minimize glucocorticosteroid use are necessary to prevent this serious complication.

Objective: To determine the level of agreement of disease flare severity (distinguishing severe, moderate, and mild flare and persistent disease activity) in a large paper-patient exercise involving 988 individual cases of systemic lupus erythematosus., Methods: A total of 988 individual lupus case histories were assessed by 3 individual physicians. Complete agreement about the degree of flare (or persistent disease activity) was obtained in 451 cases (46%), and these provided the reference standard for the second part of the study. This component used 3 flare activity instruments (the British Isles Lupus Assessment Group [BILAG] 2004, Safety of Estrogens in Lupus Erythematosus National Assessment [SELENA] flare index [SFI] and the revised SELENA flare index [rSFI]). The 451 patient case histories were distributed to 18 pairs of physicians, carefully randomized in a manner designed to ensure a fair case mix and equal distribution of flare according to severity., Results: The 3-physician assessment of flare matched the level of flare using the 3 indices, with 67% for BILAG 2004, 72% for SFI, and 70% for rSFI. The corresponding weighted kappa coefficients for each instrument were 0.82, 0.59, and 0.74, respectively. We undertook a detailed analysis of the discrepant cases and several factors emerged, including a tendency to score moderate flares as severe and persistent activity as flare, especially when the SFI and rSFI instruments were used. Overscoring was also driven by scoring treatment change as flare, even if there were no new or worsening clinical features., Conclusion: Given the complexity of assessing lupus flare, we were encouraged by the overall results reported. However, the problem of capturing lupus flare accurately is not completely solved., (© 2017, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Background: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE., Methods: We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event., Results: Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P = 0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety., Conclusions: Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.

Objective: To determine the longitudinal damage trajectory of patients with juvenile-onset systemic lupus erythematosus (SLE), and to identify baseline and disease course predictors of damage trajectory., Methods: This is a retrospective inception cohort. Longitudinal pediatric-age data were obtained from a juvenile-onset SLE research database, while adult-age data were obtained from either a research database or patients' charts. Baseline factors were tested as predictors. Time-varying factors were lagged 6-24 months before a visit for testing their predictive effects. The longitudinal damage trajectory was modeled using a weighted generalized estimating equation., Results: This study cohort consisted of 473 subjects, with followup to 26 years. A total of 65% of patients were ages >18 years at last followup. Cataracts (14%), avascular necrosis (10%), and osteoporosis (5%) were the most common items of damage. Two patients had myocardial infarctions. Baseline features, self-reported ethnicity (Afro-Caribbean), earlier time periods of diagnosis, and the presence of a life-threatening major organ manifestation (lupus nephritis class III-V, cerebrovascular accidents, major organ vasculitis, pulmonary hemorrhage, or myocarditis), were associated with greater damage. Throughout the disease course, an acute confusional state, lupus headache, and fever predicted subsequent increases in the damage trajectory. A higher prednisone dose and exposure to cyclophosphamide also predicted subsequent increases in the damage trajectory. Antimalarial exposure was protective against an increase in damage trajectory., Conclusion: Patients with juvenile-onset SLE accrue damage steadily into adulthood. Baseline factors predict greater damage and/or influence the evolution of the damage trajectory. Additionally, SLE clinical features and therapies during the course of disease predict additional changes in the damage trajectory., (© 2017, American College of Rheumatology.)

Background: Tofacitinib is an oral Janus kinase inhibitor that is under investigation for the treatment of psoriatic arthritis. We evaluated tofacitinib in patients with active psoriatic arthritis who had previously had an inadequate response to tumor necrosis factor (TNF) inhibitors., Methods: In this 6-month randomized, placebo-controlled, double-blind, phase 3 trial, we randomly assigned 395 patients, in a 2:2:1:1 ratio, to four regimens: 5 mg of tofacitinib administered orally twice daily (132 patients); 10 mg of tofacitinib twice daily (132 patients); placebo, with a switch to 5 mg of tofacitinib twice daily at 3 months (66 patients); or placebo, with a switch to 10 mg of tofacitinib twice daily at 3 months (65 patients). Data from the patients who received placebo during the first 3 months of the trial were pooled. The primary end points were the percentage of patients who had at least 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) and the change from baseline score on the Health Assessment Questionnaire-Disability Index (HAQ-DI; scores range from 0 to 3, with higher scores indicating greater disability) at the month 3 analysis., Results: At 3 months, the rates of ACR20 response were 50% with the 5-mg dose of tofacitinib and 47% with the 10-mg dose, as compared with 24% with placebo (P<0.001 for both comparisons); the corresponding mean changes from baseline in HAQ-DI score were -0.39 and -0.35, as compared with -0.14 (P<0.001 for both comparisons). Serious adverse events occurred in 4% of the patients who received the 5-mg dose of tofacitinib continuously and in 6% who received the 10-mg dose continuously. Over the course of 6 months, there were four serious infections, three herpes zoster infections, one myocardial infarction, and one ischemic stroke among the patients who received tofacitinib continuously. Elevations of aspartate and alanine aminotransferase concentrations of three or more times the upper limit of the normal range occurred in more patients who received tofacitinib continuously than in patients who received placebo followed by tofacitinib., Conclusions: In this trial involving patients with active psoriatic arthritis who had had an inadequate response to TNF inhibitors, tofacitinib was more effective than placebo over 3 months in reducing disease activity. Adverse events were more frequent with tofacitinib than with placebo. (Funded by Pfizer; OPAL Beyond ClinicalTrials.gov number, NCT01882439 .).

Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-β2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-β2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

Objectives: To evaluate disease activity in the joints and skin during pregnancy and the first-year postpartum in patients with psoriatic arthritis (PsA)., Methods: Women with PsA who were pregnant between 1990 and 2015 with at least 1 clinic visit during pregnancy were identified from the Toronto PsA database. The course of joint and skin disease activity was defined by the following 5 states: improvement, worsening, stable low, stable high, or a mixed. As controls, 67 nonpregnant PsA women were identified and evaluated over a similar timeframe., Results: Altogether, 29 PsA women with 42 pregnancies were identified. Of the 42 pregnancies, 40 (95%) resulted in normal live birth. Arthritis improved or was stable low activity in 24 (58.5%) of pregnancies. During the postpartum period, 21 (52.5%) had either improvement or stable low PsA activity, whereas 16 (40%) had either worsening or stable high disease activity. The skin activity during pregnancy either improved or stayed in a stable low state in 30 (88.2%), and in the postpartum period there was worsening in 15 (42.9%). A logistic regression analysis revealed a favourable skin disease course during the pregnancy period in the pregnant group compared to the control group (OR = 6.8, p = 0.004), but not in joint disease., Conclusions: The outcome of pregnancy among patients with PsA is excellent. Arthritis activity trends toward a favourable course while the skin disease shows a favorable course during pregnancy. When compared to controls, pregnancy period has significant beneficial influence only on the skin but not on the joints in PsA., (Copyright © 2017 Elsevier Inc. All rights reserved.)