BACKGROUND: Comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) during treatment with tumour necrosis factor inhibitors (TNFi) is extensively used in psoriatic arthritis (PsA), although the additive benefit remains unclear. We aimed to compare treatment outcomes in patients with PsA treated with TNFi and csDMARD comedication versus TNFi monotherapy. METHODS: Patients with PsA from 13 European countries who initiated a first TNFi in 2006-2017 were included. Country-specific comparisons of 1 year TNFi retention were performed by csDMARD comedication status, together with HRs for TNFi discontinuation (comedication vs monotherapy), adjusted for age, sex, calendar year, disease duration and Disease Activity Score with 28 joints (DAS28). Adjusted ORs of clinical remission (based on DAS28) at 12 months were calculated. Between-country heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Secondary analyses stratified according to TNFi subtype (adalimumab/infliximab/etanercept) and restricted to methotrexate as comedication were performed. RESULTS: In total, 15 332 patients were included (62% comedication, 38% monotherapy). TNFi retention varied across countries, with significant heterogeneity precluding a combined estimate. Comedication was associated with better remission rates, pooled OR 1.25 (1.12-1.41). Methotrexate comedication was associated with improved remission for adalimumab (OR 1.45 (1.23-1.72)) and infliximab (OR 1.55 (1.21-1.98)) and improved retention for infliximab. No effect of comedication was demonstrated for etanercept. CONCLUSION: This large observational study suggests that, as used in clinical practice, csDMARD and TNFi comedication are associated with improved remission rates, and specifically, comedication with methotrexate increases remission rates for both adalimumab and infliximab.

1st Faculty of Medicine Charles University Prague Czech Republic

Centre for Rheumatology Research University Hospital Reykjavik Iceland

Clinical Epidemiology Division Department of Medicine Solna Karolinska Institutet Stockholm Sweden

Copenhagen Center for Arthritis Research Center for Rheumatology and Spine Diseases Centre for Head and Orthopaedics Rigshospitalet Glostrup Glostrup Denmark

DANBIO and Copenhagen Center for Arthritis Research Center for Rheumatology and Spine Diseases Centre of Head and Orthopedics Rigshospitalet Copenhagen Denmark

Department for Rheumatology and Immunology Inselspital University Hospital Bern Bern Switzerland

Department for Science and Research Landspitali University Hospital Reykjavik Iceland

Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Rheumatology 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Rheumatology and Inflammation Research Sahlgrenska Academy University of Gothenburg Gothenburg Sweden

Department of Rheumatology and Research Diakonhjemmet Hospital Oslo Norway

Department of Rheumatology Geneva University Hospital Geneva Switzerland

Department of Rheumatology University Hospital Zurich University of Zurich Zurich Switzerland

Department of Rheumatology University Medical Centre Ljubljana Ljubljana Slovenia

Division of Rheumatology Department of Internal Medicine University Hospital and Faculty of Medicine Gazi University Ankara Turkey

Division of Rheumatology Department of Internal Medicine University Hospital and Faculty of Medicine Inonu University Malatya Turkey

Division of Rheumatology Department of Medicine Sorlandet Hospital Kristiansand Norway

Epidemiology Group Aberdeen Centre for Arthritis and Musculoskeletal Health University of Aberdeen Aberdeen UK

Faculty of Medicine University of Iceland Reykjavik Iceland

Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Inflammation Center Department of Rheumatology Helsinki University Hospital Helsinki Finland

Institute of Biostatistics and Analyses Ltd Brno Czech Republic

Institute of Rheumatology Prague Czech Republic

Orton Orthopaedic Hospital Helsinki Finland

Research Unit Spanish Society of Rheumatology Madrid Spain

Reuma pt registry and Department of Rheumatology Hospital Garcia de Orta Almada Portugal

Rheumatology Department Hospital de Santa Maria Lisboa Portugal

Rheumatology Research Unit Instituto de Medicina Molecular Faculdade de Medicina Universidade de Lisboa Lisboa Portugal

Rheumatology Service Hospital Clinico Universitario Santiago de Compostela Spain

Rheumatology Unit DETO University of Bari Bari Italy

Romanian Registry of Rheumatic Diseases University of Medicine and Pharmacy Bucharest Romania

Romanian Registry of Rheumatic Diseases University of Medicine and Pharmacy Carol Davila Bucharest Romania

Zobrazit více v PubMed

Singh JA, Guyatt G, Ogdie A, et al. . Special article: 2018 American College of Rheumatology/National psoriasis Foundation guideline for the treatment of psoriatic arthritis. Arthritis Rheumatol 2019;71:5–32. 10.1002/art.40726 PubMed DOI PMC

Gossec L, Baraliakos X, Kerschbaumer A, et al. . EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis 2020;79:700.1–12. 10.1136/annrheumdis-2020-217159 PubMed DOI PMC

Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med 2017;376:957–70. 10.1056/NEJMra1505557 PubMed DOI

Kingsley GH, Kowalczyk A, Taylor H, et al. . A randomized placebo-controlled trial of methotrexate in psoriatic arthritis. Rheumatology 2012;51:1368–77. 10.1093/rheumatology/kes001 PubMed DOI PMC

Baranauskaite A, Raffayová H, Kungurov NV, et al. . Infliximab plus methotrexate is superior to methotrexate alone in the treatment of psoriatic arthritis in methotrexate-naive patients: the respond study. Ann Rheum Dis 2012;71:541–8. 10.1136/ard.2011.152223 PubMed DOI PMC

Coates LC, Moverley AR, McParland L, et al. . Effect of tight control of inflammation in early psoriatic arthritis (TICOPA): a UK multicentre, open-label, randomised controlled trial. Lancet 2015;386:2489–98. 10.1016/S0140-6736(15)00347-5 PubMed DOI PMC

Willkens RF, Williams HJ, Ward JR, et al. . Randomized, double-blind, placebo controlled trial of low-dose pulse methotrexate in psoriatic arthritis. Arthritis Rheum 1984;27:376–81. 10.1002/art.1780270403 PubMed DOI

Scarpa R, Peluso R, Atteno M, et al. . The effectiveness of a traditional therapeutical approach in early psoriatic arthritis: results of a pilot randomised 6-month trial with methotrexate. Clin Rheumatol 2008;27:823–6. 10.1007/s10067-007-0787-7 PubMed DOI

Mease PJ, Gladman DD, Collier DH, et al. . Etanercept and methotrexate as monotherapy or in combination for psoriatic arthritis: primary results from a randomized, controlled phase III trial. Arthritis Rheumatol 2019;71:1112–24. 10.1002/art.40851 PubMed DOI PMC

Behrens F, Cañete JD, Olivieri I, et al. . Tumour necrosis factor inhibitor monotherapy vs combination with MTX in the treatment of PsA: a systematic review of the literature. Rheumatology 2015;54:915–26. 10.1093/rheumatology/keu415 PubMed DOI

George MD, Baker JF, Ogdie A. Comparative persistence of methotrexate and tumor necrosis factor inhibitors in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. J Rheumatol 2020;47:826–34. 10.3899/jrheum.190299 PubMed DOI PMC

Kristensen LE, Gülfe A, Saxne T, et al. . Efficacy and tolerability of anti-tumour necrosis factor therapy in psoriatic arthritis patients: results from the South Swedish arthritis treatment group register. Ann Rheum Dis 2008;67:364–9. 10.1136/ard.2007.073544 PubMed DOI

Fagerli KM, Lie E, van der Heijde D, et al. . The role of methotrexate co-medication in TNF-inhibitor treatment in patients with psoriatic arthritis: results from 440 patients included in the NOR-DMARD study. Ann Rheum Dis 2014;73:132–7. 10.1136/annrheumdis-2012-202347 PubMed DOI

Maneiro JR, Souto A, Salgado E, et al. . Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis. RMD Open 2015;1:e000017. 10.1136/rmdopen-2014-000017 PubMed DOI PMC

Brahe CH, Ørnbjerg LM, Jacobsson L, et al. . Retention and response rates in 14 261 PsA patients starting TNF inhibitor treatment-results from 12 countries in EuroSpA. Rheumatology 2020;59:1640–50. 10.1093/rheumatology/kez427 PubMed DOI

Michelsen B, Sexton J, Smolen JS, et al. . Can disease activity in patients with psoriatic arthritis be adequately assessed by a modified disease activity index for psoriatic arthritis (DAPSA) based on 28 joints? Ann Rheum Dis 2018;77:1736–41. 10.1136/annrheumdis-2018-213463 PubMed DOI

Higgins JPT, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539–58. 10.1002/sim.1186 PubMed DOI

Mease PJ, Kivitz AJ, Burch FX, et al. . Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum 2004;50:2264–72. 10.1002/art.20335 PubMed DOI

Antoni CE, Kavanaugh A, Kirkham B, et al. . Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT). Arthritis Rheum 2005;52:1227–36. 10.1002/art.20967 PubMed DOI

Mease PJ, Gladman DD, Ritchlin CT, et al. . Adalimumab for the treatment of patients with moderately to severely active psoriatic arthritis: results of a double-blind, randomized, placebo-controlled trial. Arthritis Rheum 2005;52:3279–89. 10.1002/art.21306 PubMed DOI

Glintborg B, Østergaard M, Dreyer L, et al. . Treatment response, drug survival, and predictors thereof in 764 patients with psoriatic arthritis treated with anti-tumor necrosis factor α therapy: results from the nationwide Danish DANBIO registry. Arthritis Rheum 2011;63:382–90. 10.1002/art.30117 PubMed DOI

Thomas ML, Shaddick G, Charlton R, et al. . Tumor necrosis factor inhibitor monotherapy versus combination therapy for the treatment of psoriatic arthritis: combined analysis of European biologics databases. J Rheumatol 2021;48:48–57. 10.3899/jrheum.190815 PubMed DOI

Differences in the response to TNF inhibitors at distinct joint locations in patients with psoriatic arthritis: results from nine European registries

Recording of non-musculoskeletal manifestations, comorbidities and safety outcomes in European spondyloarthritis registries: a survey

Effectiveness of secukinumab in radiographic and non-radiographic axial spondyloarthritis: a European routine-care observational study

Predictors of DAPSA28 remission in patients with psoriatic arthritis initiating a first TNF inhibitor: results from 13 European registries

Commonalities and differences in set-up and data collection across European spondyloarthritis registries - results from the EuroSpA collaboration

Differences and similarities between the EULAR/ASAS-EULAR and national recommendations for treatment of patients with psoriatic arthritis and axial spondyloarthritis across Europe