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

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.