Background Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) treatment, although limitations of systemic exposure of oral MTX may affect its efficacy. Subcutaneous (SC) MTX has greater bioavailability than oral MTX, which may result in better efficacy and tolerability. Few clinical studies have assessed the efficacy and tolerability of SC MTX.
Objectives To assess the clinical effectiveness and tolerability of SC MTX among patients with RA who were naïve at baseline to both conventional and biologic disease-modifying anti-rheumatic drugs (DMARDs) at the St. Gallen Hospital in Switzerland.
Methods Patients with RA who were DMARD-naïve, fulfilled the ACR/EULAR-2010 criteria, and had ≥1 follow-up visit were selected through sequential chart review until 70 patients were identified, using a prospectively designed retrospective analysis. Patients received SC MTX at varying doses (10-25 mg/week, mean 18.2 mg) with 5 mg folic acid weekly. The primary endpoint was a change in DAS28(ESR); secondary endpoints included time to employment of the first biologic agent and cumulative MTX doses. Patients were followed until SC MTX administration was terminated or until their last clinical visit. The decision for adding biologic agents was made at the discretion of the treating physician.
Results The 70 patients identified remained in follow-up for a mean ± SD of 1.8±1.6 years (range, 0.13-7.1) after initiating SC MTX treatment. During this time 33 (47%) required the addition of a biologic therapy (BIO+MTX), and 37 (53%) remained on SC MTX without any biologics (SC MTX). Mean weekly MTX doses were 19.1 mg for BIO+MTX patients and 17.4 mg for SC MTX patients. Compared to SC MTX patients, BIO+MTX patients were more frequently female (63.6% vs 51.4%), and less frequently ACPA-positive at baseline (33.3% vs 51.4%). Mean baseline DAS28 scores were 4.9 (range 2.42-7.4) for BIO+MTX patients and 4.7 (range 1.6-7.7) for SC MTX patients. During follow-up, BIO+MTX patients had a higher DAS28 score (mean ± 95% CI) than SC MTX patients (see figure). Both LDAS and remission were achieved by slightly fewer BIO+MTX than SC MTX patients (LDAS, 78.8% vs 81.1%; remission, 69.7% vs 75.7%). Among BIO+MTX patients, biologic therapy was required after a mean ± SD of 387±404 days (range 54-2164). Over the full course of the study period, SC MTX was discontinued in 32 patients (46%). Among those who discontinued, the most common reasons were gastrointestinal discomfort (n=7), inefficacy (n=7), disease remission (n=3), patient's decision (n=3), interstitial lung disease (n=1), and cough (n=1). Severe infections occurred in 3/33 (9%) of BIO+MTX patients and in 3/37 (8%) of SC MTX patients.
Conclusions This study supports SC MTX as an effective and well-tolerated treatment option for patients with RA in real life. Remission was achieved by a majority of patients following the initiation of SC MTX, and the addition of biologics was not needed throughout the study period for approximately half of patients. SC MTX delayed the need for biologic therapy for approximately 1 year for almost half of the patients identified.
Disclosure of Interest : None declared