Although oral MTX for the treatment of RA has been shown to be effective, adverse events may lead to discontinuation of treatment. This study reports the 24-week comparison of the safety and efficacy of subcutaneous (sc) vs orally administered MTX in patients with active RA. Patients with insufficient oral responses were switched to sc application or dose augmentation after 4 months.

Patients were randomly assigned to 15 mg oral MTX (two 7.5 mg tablets + a dummy pre-filled syringe) or sc MTX (15 mg via a pre filled syringe at 10mg/ml + dummy tablets) given weekly until week 24. At week 16 ACR20 nonresponders were switched from oral MTX to 15 mg sc and from 15 mg MTX sc to 20 mg sc for the remaining 8 weeks in a blinded fashion, respectively. The primary outcome parameters were the ACR20 after 24 weeks. Secondary outcome parameters were ACR50/70/90 and DAS28/EULAR response criteria after 24 weeks, and time to onset of ACR20.

Only 15% of the patients were classified as ACR20 nonresponders at week 16 and switched medication. After 24 weeks the sc route of MTX application yielded a significantly higher efficacy in various relevant parameters including improvement in ACR20/50/70 response rates and EULAR response rates compared to the oral administration. Remission (defined as DAS28 <2.6) was achieved by 34% of the sc MTX patients compared with 24% of the oral MTX treated patients (p<0.05).

In this first of kind study, the authors concluded that MTX given sc is significantly more effective than the oral form.