How to treat patients with rheumatoid arthritis when methotrexate has failed? The use of a multiple propensity score to adjust for confounding by indication in observational studies

Ann Rheum Dis. 2019 Jan;78(1):25-30. doi: 10.1136/annrheumdis-2018-213731. Epub 2018 Oct 16.


Objectives: To compare consecutive disease modifying antirheumatic drug (DMARD)-treatment regimes in daily practice in patients with rheumatoid arthritis (RA) who failed on initial methotrexate, while using a multiple propensity score (PS) method to control for the spurious effects of confounding by indication.

Methods: Patients with newly diagnosed RA who had failed initial treatment with methotrexate were selected from METEOR, an international, observational registry. Subsequent DMARD-treatment regimens were categorised as: (1) conventional synthetic DMARD(s) (csDMARD(s)) only (143 patients), (2) csDMARD(s)+glucocorticoid (278 patients) and (3) biological DMARD (bDMARD)±csDMARD(s) (89 patients). Multiple PS that reflect the likelihood of treatment with each treatment-regime were estimated per patient using multinomial regression. Linear mixed model analyses were performed to analyse treatment responses per category (Disease Activity Score (DAS)) after a maximum follow-up duration of 6 and 12 months, and results were presented with adjustment for the multiple PS.

Results: After 6 months, follow-up PS-adjusted treatment responses yielded a change in DAS per year (95% CI) of -2.00 (-2.65 to -1.36) if patients received a bDMARD; of -0.96 (-1.33 to -0.59) if patients received csDMARD(s)+glucocorticoids and of -0.73 (-1.21 to -0.25) if patients received csDMARDs only. These changes were -0.91 (-1.23 to -0.60); -0.43 (-0.62 to -0.23) and -0.39 (-0.66 to -0.13), respectively after 1 year of follow-up.

Conclusions: In this analysis of worldwide common practice data with adjustment for multiple PS, patients with RA who had failed initial treatment with methotrexate monotherapy had a better DAS-response after a subsequent switch to a bDMARD-containing treatment regimen than to a regimen with csDMARD(s) only, with or without glucocorticoids.

Keywords: disease activity; methotrexate; rheumatoid arthritis; treatment.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Biological Products / therapeutic use*
  • Clinical Protocols
  • Drug Substitution
  • Drug Therapy, Combination
  • Female
  • Humans
  • Linear Models
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Observational Studies as Topic
  • Patient Selection
  • Propensity Score
  • Registries
  • Treatment Outcome


  • Antirheumatic Agents
  • Biological Products
  • Methotrexate