OBJECTIVE: To investigate whether tumor necrosis factor inhibitor (TNFi) combination therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) is more effective for psoriatic arthritis (PsA) and/or improves TNFi drug survival compared to TNFi monotherapy. METHODS: Five PsA biologics cohorts were investigated between 2000 and 2015: the ATTRA registry (Czech Republic); the Swiss Clinical Quality Management PsA registry; the Hellenic Registry of Biologics Therapies (Greece); the University of Bari PsA biologics database (Italy); and the Bath PsA cohort (UK). Drug persistence was analyzed using Kaplan-Meier and equality of survival using log-rank tests. Comparative effectiveness was investigated using logistic regression with propensity scores. Separate analyses were performed on (1) the combined Italian/Swiss cohorts for change in rate of Disease Activity Score in 28 joints (DAS28); and (2) the combined Italian, Swiss, and Bath cohorts for change in rate of Health Assessment Questionnaire (HAQ). RESULTS: In total, 2294 patients were eligible for the drug survival analysis. In the Swiss (P = 0.002), Greek (P = 0.021), and Bath (P = 0.014) databases, patients starting TNFi in combination with methotrexate had longer drug survival compared to monotherapy, while in Italy the monotherapy group persisted longer (P = 0.030). In eligible patients from the combined Italian/Swiss dataset (n = 1056), there was no significant difference between treatment arms in rate of change of DAS28. Similarly, when also including the Bath cohort (n = 1205), there was no significant difference in rate of change of HAQ. CONCLUSION: Combination therapy of a TNFi with a csDMARD does not appear to affect improvement of disease activity or HAQ versus TNFi monotherapy, but it may improve TNFi drug survival.

A Drosos MD PhD Rheumatology Clinic Department of Internal Medicine Medical School University of Ioannina Ioannina Greece

A Nightingale PhD Department of Pharmacy and Pharmacology University of Bath Bath UK

A Scherer PhD SCQM Foundation Zürich Switzerland N McHugh and A Nightingale are joint senior authors

B Möller Professor Department of Rheumatology Immunology and Allergology Inselspital University Hospital Bern Bern Switzerland

C Cavill BSc R Holland MD Royal National Hospital for Rheumatic Diseases Bath UK

F Iannone MD PhD G Lapadula MD S Lopriore MD Rheumatology Unit DETO University of Bari Bari Italy

G Shaddick PhD Department of Mathematics University of Exeter Exeter UK

J Závada MD PhD K Pavelka MD PhD Institute of Rheumatology Prague Czech Republic

M J Nissen MBBS FRACP Department of Rheumatology University Hospital Geneva Geneva Switzerland

M L Thomas PhD Department of Mathematical Science University of Bath Bath UK

M Uher MSc L Szczuková MD Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic

P Sidiropoulos MD PhD 1 Flouri MD Rheumatology Clinical Immunology and Allergy Department Medical School University of Crete Crete Greece

R B Müller MD Cantonal Hospital Lucerne Switzerland

R Charlton PhD N McHugh MBChB MD FRCP FRCPath Department of Pharmacy and Pharmacology University of Bath Bath UK

R Charlton PhD N McHugh MBChB MD FRCP FRCPath Department of Pharmacy and Pharmacology University of Bath Bath UK;

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Effectiveness and treatment retention of TNF inhibitors when used as monotherapy versus comedication with csDMARDs in 15 332 patients with psoriatic arthritis. Data from the EuroSpA collaboration