Non-adherence to methotrexate was associated with high disease activity and poor health-related outcomes during a 4-year follow-up of rheumatoid arthritis patients.

Objectives: Although methotrexate (MTX) is the first-line drug for management of rheumatoid arthritis (RA), non-adherence to MTX is highly prevalent and under-recognised. Here, we investigated adherence to MTX and its impact on clinical outcomes during follow-up in patients with RA.

Methods: In total, 367 RA patients were included in this study, with patient visits conducted annually for 4 consecutive years. Adherence was defined by the medication possession ratio during the follow-up period. We divided the patients into two groups; patients who took ≥80% of their prescribed MTX doses and those who did not. In a prospective cohort, the generalised estimating equations were used to identify longitudinal associations between drug adherence and clinical outcomes including disease activity, physical function, and quality of life.

Results: Of the 367 RA patients, 8.7% were found to have taken MTX <80% during the period of follow up. After adjustment for confounders, non-adherence to MTX was significantly associated with higher DAS28-ESR during the follow-up period (coefficient β=0.989, 95%; CI: 0.603-1.375; p<0.001). In addition, non-adherence to MTX was a significant predictor of RAPID3 (coefficient β=1.847; 95% CI: 0.221-3.472; p=0.026) and EQ-5D (coefficient β= -0.051; 95% CI: -0.090-0.012; p=0.010) after adjustment for confounding factors.

Conclusions: Non-adherence to MTX was significantly associated with worse clinical outcomes, as evidenced by higher disease activity, poorer physical function, and lower health-related quality of life during a 4-year follow-up of RA patients.