Effect of Methotrexate Plus Adalimumab on the Achievement of Rheumatoid Arthritis Therapeutic Goals: Post Hoc Analysis of Japanese Patients (MELODY Study)

Abstract

Introduction: There is insufficient evidence regarding the appropriate dose of methotrexate (MTX) required to achieve specific treatment goals in patients with rheumatoid arthritis (RA) receiving biologic drugs in Japan. The present study aimed to assess the dose-response effect of MTX in combination with adalimumab (ADA) to achieve low disease activity (LDA) and/or remission at 24 weeks in RA patients.

Methods: This analysis used data of the ADA all-case survey in Japan (n = 7740), and 5494 patients who received ADA and MTX were classified into five groups by weighted average MTX dose (>0-<4, 4-<6, 6-<8, 8-< 10, and ≥10 mg/week). Of the 5494 patients, 3097 with baseline 28-joint disease activity score based on erythrocyte sedimentation rate >3.2 were analyzed for effectiveness by MTX dose.

Results: In biologic-naïve patients (n = 1996/3097), LDA/remission rates increased with MTX up to 6-<8 mg/week and then plateaued at higher doses (LDA, p = 0.0440; remission, p = 0.0422). In biologic-exposed patients (n = 1101/3097), LDA/remission rates increased with MTX dose (LDA, p = 0.0009; remission p = 0.0143). The incidences of serious adverse drug reactions (ADRs) and serious infections did not differ by MTX dose, but total ADRs and infections were significantly higher (p < 0.05) with increased MTX doses.

Conclusion: The appropriate MTX doses in combination with ADA to achieve LDA and/or remission at week 24 were different between biologic-naïve and biologic-exposed patients with RA, suggesting that 8 mg/week of MTX would be enough for biologic-naïve patients.

Trial registration: ClinicalTrials.gov identifier, NCT01076959.

Funding: AbbVie and Eisai Co., Ltd.

Keywords: Adalimumab; Doses; Effectiveness; Methotrexate; Rheumatoid arthritis; Safety.

Figures

Fig. 1

Percentages of patients achieving LDA (A) and remission rate (B) after treatment with MTX and adalimumab for 24 weeks. Patients were stratified by weighted average dose of concomitant weekly MTX as follows: group 1, >0–<4 mg; group 2, 4–<6 mg; group 3, 6–<8 mg; group 4, 8–<10 mg; and group 5, ≥10 mg; one degree of freedom for each. aAIC, 2479.177. Contrast test results adjusted for baseline DAS28-ESR (continuous), age (1: <20 years, 2: 20–29 years, 3: 30–39 years, 4: 40–49 years, 5: 50–59 years, 6: 60–69 years, 7: 70–79 years, and 8: ≥80 years; continuous), class (I–II, III–IV), previous or coexisting diabetes mellitus (yes, no), and sex. Patients received any biologic treatment other than adalimumab before starting adalimumab treatment; bAIC, 1116.088. Contrast test results adjusted for baseline DAS28-ESR (continuous), class (I–II, III–IV), sex, and past biologic treatment (infliximab only, etanercept only, both infliximab and etanercept, and any others). AIC, Akaike’s information criterion. DAS28-ESR disease activity score for 28 joint counts based on the erythrocyte sedimentation rate, LDA low disease activity, MTX methotrexate. Values are expressed as mean ± standard deviation