Effect of Concomitant Disease-modifying Antirheumatic Drugs and Methotrexate Administration Route on Biologic Treatment Durability in Rheumatoid Arthritis: OBRI Cohort Results

J Rheumatol. 2019 Aug;46(8):874-886. doi: 10.3899/jrheum.180486. Epub 2019 Apr 15.

Abstract

Objective: Prior studies have suggested that concurrent conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy enhances the efficacy of biologic DMARD (bDMARD). Here, we assessed the effect of concomitant csDMARD use and methotrexate (MTX) route of administration on time to bDMARD discontinuation in a large Canadian (Ontario), observational, rheumatoid arthritis (RA) cohort.

Methods: Patients from the Ontario Best Practices Research Initiative (OBRI) who initiated bDMARD therapy and had ≥ 1 followup assessment were included. The effect of concomitant csDMARD use (primary analysis) and MTX route of administration (secondary analysis) on bDMARD discontinuation owing to (1) any reason, (2) ineffectiveness, (3) adverse events (AE), and (4) both (2) and (3), were assessed with multivariate Cox regression.

Results: Among the 814 patients included, 153 (18.8%) received bDMARD monotherapy and 661 (81.2%) combination csDMARD/bDMARD therapy. Over a mean followup of 1.9 years, bDMARD were discontinued in 38.7% of patients. In multivariate analysis, there was a nonsignificant trend toward lower discontinuation for the csDMARD/bDMARD group compared to bDMARD monotherapy for any reason (HR 0.76, 95% CI 0.55-1.05) and owing to ineffectiveness/AE (HR 0.73, 95% CI 0.50-1.06). Further, patients taking combination therapy had significantly lower risk of bDMARD discontinuation due to AE (HR 0.43, 95% CI 0.24-0.76). In the secondary analysis, no statistical association between MTX dose or route of administration and bDMARD durability was observed.

Conclusion: Concomitant csDMARD use was associated with a significantly lower hazard for bDMARD discontinuation due to AE among patients with RA followed in routine clinical practice in Ontario, Canada. Neither MTX route of administration nor dose were significant predictors of bDMARD durability.

Keywords: BIOLOGIC THERAPY; DISEASE-MODIFYING ANTIRHEUMATIC DRUG; LONGITUDINAL STUDIES; METHOTREXATE; REGISTRIES.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biological Products / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Biological Products
  • Methotrexate