Background In general, the concomitant use of methotrexate (MTX) and biologic disease-modifying antirheumatic drugs (DMARDS) plays an important role in treatment for bio-naïve patients with rheumatoid arthritis (RA). However, it remains unclear whether concomitant use of MTX is related to the effects of treatment with second biologic DMARDS in RA patients for whom first biologic DMARDS therapy have failed.
Objectives The objective of the current study was to determine whether, and if so to what extent, concomitant use of MTX was associated with the effects of treatment with second biologic DMARDS, especially in the context of whether or not tumor necrosis factor inhibitor (TNFi) had been used.
Methods We used demographic and clinical data from the Tsurumai Biologics Communication Registry, which comprises Nagoya University and 20 affiliated hospitals in Japan. Patients aged 20–80 years who fulfilled the ACR 1987 revised classification criteria or the 2010 ACR/EULAR classification criteria for RA were selected; only those switching to second biologic DMARDS therapy were included. Multivariate logistic regression analysis was used to assess the association between MTX use and the possibility of sufficient response to second biologic DMARDS treatment, as defined by good response at week 16 in the EULAR response criteria, based on DAS28. Crude and adjusted odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were calculated. Adjustment variables included sex, age, disease duration, whether or not TNFi had been used in RA treatments with first and second biologic DMARDS, use of MTX in first biologic treatment, and use of glucocorticoids in treatment with second biologic DMARDS. We determined the statistical significance of potential subgroup effect of whether or not TNFi had been used as second biologics by testing the significance of the interaction terms added to our multivariable models.
Results The demographic and disease characteristics of the patients at baseline were comparable except for the proportion of TNFi between patients not using MTX (n=49) and those treated concomitantly with MTX (n=122). The mean age was 59 years; 86% were women. Patients had longstanding RA (mean 10.6 years), and the baseline DAS28 was 5.2. Among the patients, 68% received glucocorticoids. The mean dose of MTX was 8.0 mg/week in patients using MTX. The proportion of TNFi was 26.5% in patients not using MTX and 62.3% in those using MTX, respectively. A good response as per EULAR response criteria was identified in 14 (28.6%) patients not using MTX and 58 (47.5%) patients treated concomitantly with MTX. The crude OR for the association between concomitant use of MTX and the possibility of good response as per EULAR response criteria was 2.27 (95% CI 1.11–4.63) compared with nonuse of MTX. After adjustment for the aforementioned covariates, concomitant use of MTX was associated with an increased possibility of good response to biologic DMARDS compared with nonuse of MTX (OR 2.77, 95% CI 1.04–7.36). This multivariable adjusted effect estimate was not modified by whether or not TNFi had been used (P value for interaction greater than 0.05).
Conclusions This study demonstrated that concomitant use of MTX was independently associated with an increased possibility of good response to second biologic DMARDS regardless of whether or not TNFi had been used in RA treatment.
Disclosure of Interest None declared