Does Biologic Survival Depend on Co-prescribed Methotrexate Dose in Established Rheumatoid Arthritis? A Real-world Study


Several seminal studies have suggested that a combination therapy of biologics with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) improve disease outcomes in rheumatoid arthritis (RA). Hence, most guidelines reflect this practice. It has also been shown that methotrexate (MTX) at a dose of 8-10 mg/week is perhaps sufficient to achieve better outcomes in early RA. However, it is not clear whether this strategy enhances biologic retention in the patients with established RA. We present a real-world retrospective study to investigate whether csDMARD co-prescription improves biologic retention and the optimal dose to preserve such response.


All patients prescribed biologic therapy for RA at our center between 2003 and 2017 were identified through the departmental database. They were split into five groups based on a weekly MTX dose (≤7.5 mg, 10-17.5 mg, ≥20 mg), other csDMARD prescription, or biologic monotherapy. The one-way analysis of variance model for independent values was utilized to ascertain the significance of data. The Mann-Whitney two-tailed U test was employed to determine the significance of relationship between the monotherapy group and other arms. The significance level was predefined at 0.05.


A total of 168 patients with 198 biologic events were included. The mean age was 59.4 years (range, 24-90 years). 78% were women. The mean disease duration was 155.6 months (range, 15-491). There was a statistically significant difference (p=0.03) in biologic retention among the five arms. Compared to monotherapy, the data remained significant for ≥20 mg MTX and csDMARD groups; however, the biologic retention in the other two MTX arms was not significant. There was no significant relationship among groups for DAS28 improvement (p=0.24).


Our results suggest that to improve biologic retention, the MTX dose should be increased to 20 mg a week or more, and, in people with MTX intolerance, csDMARDs co-presciption can be an alternative strategy. Maintenance with a low-to-moderate MTX dose can lead to poorer retention rates.

 2019 Nov 25:1-4. doi: 10.5152/eurjrheum.2019.19048. [Epub ahead of print]