Background/Purpose: MTX is the cornerstone of 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. We assess the clinical effectiveness and tolerability of SC MTX among pts with RA naïve at baseline to both conventional and biologic DMARDs at our center.

Methods: DMARD-naïve RA pts fulfilling the ACR/EULAR-2010 criteria and had ≥ 1 follow-up visit were selected through sequential chart review until 70 were identified using a prospectively designed retrospective analysis. Pts received SC MTX at varying doses (10-25 mg/week, mean 18.2 mg) w/ 5 mg folic acid/wk. The primary endpoint was a change in DAS28 (ESR); secondary endpoints included time to employment of the first biologic agent and cumulative MTX doses. Pts were followed until SC MTX administration was terminated or their last clinical visit. Decision for adding biologic agents was at the discretion of the treating physician.

Results:  70 pts 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 pts and 17.4 mg for SC MTX pts. Compared to SC MTX pts, BIO+MTX pts 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 pts and 4.7 (range 1.6-7.7) for SC MTX pts. During follow-up, BIO+MTX pts had a higher DAS28 score (mean ± 95% CI) than SC MTX pts (see figure). Both LDAS and remission were achieved by slightly fewer BIO+MTX than SC MTX pts (LDAS, 78.8% vs 81.1%; remission, 69.7% vs 75.7%). Among BIO+MTX pts, biologic therapy was required after a mean ± SD of 387 ± 404 days (range 54-2164). Over the the study period, SC MTX was discontinued in 32 pts (46%). Most common discontinuation 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 pts and in 3/37 (8%) of SC MTX pts.

Conclusion: SC MTX is an effective, well-tolerated option for pts with RA in real life. Remission was achieved by a majority of pts following the initiation of SC MTX, and the addition of biologics was not needed throughout the study period for about half of pts. SC MTX delayed need for biologic therapy for about 1 year for almost half of the pts.