Abstract

Background:Hand osteoarthritis (OA) is characterized by bone erosions, joint space remodeling, and new bone formation mainly in distal interphalangeal (DIP) joints and thereby differs from hand manifestations in rheumatoid arthritis (RA). There are conflicting data about the benefit of treatment with conventional synthetic (cs) and biologic (b) disease modifying anti-rheumatic treatment (DMARD) on DIP OA.Objectives:To assess the associations between DMARDs and incident, and progression of, radiographic DIP OA in RA patients.Methods:We performed two observational cohort studies in the longitudinal Swiss Clinical Quality Management in Rheumatic Diseases registry (SCQM) between 1997 and 2014. RA patients who had ≥2 eligible hand radiographs were included at their first eligible radiograph (baseline) and were followed until the outcome or their last eligible radiograph. Radiographs were eligible if all 8 DIP joints could be scored. Modified Kellgren-Lawrence scores (KLS) were obtained by evaluating DIP joints for severity of osteophytes, joint space narrowing, subchondral sclerosis, and erosions. Incident/existing DIP OA was defined as KLS ≥2 in ≥1 DIP joint. Progression of existing DIP OA was defined as an increase of ≥1 in KLS in ≥1 DIP joint. We divided the study population into two cohorts based on whether DIP OA was present or absent at cohort entry (cohorts 1 and 2, respectively). Exposure status was defined time-dependently into mutually exclusive exposure groups: csDMARD monotherapy, bDMARD monotherapy, bDMARD/csDMARD combination therapy, past bDMARD/csDMARD therapy, or never DMARD use. Cox time-varying proportional hazard regression analyses were used to estimate hazard ratios (HRs) with 95% confidence intervals (CI) of DIP OA progression (cohort 1) or DIP OA incidence (cohort 2) associated with DMARD exposure categories (csDMARD monotherapy was the reference group because it was the largest group). Exposure and covariate information were extracted at every radiograph and other visit date. Missing covariate information was imputed using multiple imputation by chained equations. In sensitivity analyses, we repeated all analyses using generalised estimation equations (GEE).Results:Among 2234 RA patients with 5928 eligible radiographs, 1340 patients had radiographic DIP OA at cohort entry (cohort 1) and 894 were DIP OA naïve (cohort 2). In cohort 1, radiographic progression of existing DIP OA was characterized by new osteophyte formation (666, 52.4%), followed by joint space narrowing (379, 27.5%), subchondral sclerosis (238, 17.8%), and erosion (62, 4.3%). bDMARD monotherapy was associated with an increased risk of radiographic DIP OA progression compared to csDMARD monotherapy (adjusted HR 1.34, 95% CI 1.07–1.69). The risk of DIP OA progression was not significant in csDMARD/bDMARD combination therapy users (adjusted HR 1.12, 95% CI 0.96–1.31), absent in past DMARD users (adjusted HR 0.96, 95% CI 0.66–1.41), and significantly lower among never DMARD users (adjusted HR 0.54, 95% CI 0.33–0.90), compared to csDMARD monotherapy users. In cohort 2, the risk of incident OA did not differ materially between treatment groups. Results from GEE analyses corroborated all findings.Conclusion:Our results from this real-world RA cohort suggest that monotherapy with bDMARDs is not associated with incident DIP OA but may increase the risk of radiographic progression of existing DIP OA when compared to csDMARDs.Acknowledgements:We thank all patients and rheumatologists involved for their contribution to the SCQM RA cohort. A list of rheumatology offices and hospitals that contribute to the SCQM registry can be found at http://www.scqm.ch/institutions. The SCQM is financially supported by pharmaceutical industries and donors. A list of financial supporters can be found at http://www.scqm.ch/sponsors.Disclosure of Interests:Theresa Burkard: None declared, Christian Lechtenboehmer: None declared, Stephan Reichenbach: None declared, Monika Hebeisen: None declared, Ulrich Walker: None declared, Andrea Michelle Burden: None declared, Thomas Hügle Consultant of: Pfizer, Abbvie, Novartis, Grant/research support from: GSK, Jansen, Pfizer, Abbvie, Novartis, Roche, MSD, Sanofi, BMS, Eli Lilly, UCB

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