Comorbidities and chance of remission in patients with early rheumatoid arthritis receiving methotrexate as first-line therapy: a Swedish observational nationwide study

Objectives This study aims to examine whether comorbidities affect the likelihood of reaching primary remission on methotrexate monotherapy as the first disease-modifying antirheumatic drug (DMARD) in early rheumatoid arthritis (RA).Methods We used nationwide Swedish clinical and quality registers to collect RA disease activity measures and comorbidity data for patients diagnosed with RA 2007–2020 (n=11 001). The primary outcome was failure to reach 28-joint Disease Activity Score (DAS28) remission at 3 months. Secondary outcomes included Boolean, Simplified Disease Activity Index/Clinical Disease Activity Index remission, European Alliance of Associations for Rheumatology response and no swollen joint count at 3 and 6 months. For each comorbidity, and for combinations thereof, we calculated adjusted relative risks (RRs) of failure to reach remission, using modified Poisson regression.Results In total, 53% (n=4019/7643) failed to reach DAS28 remission after 3 months of methotrexate monotherapy, ranging from 66% (n=25/38) among patients with chronic kidney disease to 48% (n=154/319) in patients with previous cancer. The risk of not reaching DAS28 remission at 3 months (RR adjusted for sex and age) was increased among patients with endocrine (RR 1.08, 95% CI 1.01 to 1.15), gastrointestinal (RR 1.16, 95% CI 1.03 to 1.30), infectious (RR 1.21, 95% CI 1.06 to 1.38), psychiatric (RR 1.24, 95% CI 1.15 to 1.35) and respiratory comorbidities (RR 1.16, 95% CI 1.01 to 1.32). Having three or more comorbidity categories was associated with a 27% higher risk of DAS28 remission failure at 3 months. A similar pattern was observed for the secondary outcomes.Conclusions Comorbidities decrease the chance of reaching remission on methotrexate as DMARD monotherapy in patients with early RA and are important to consider when assessing treatment outcomes.