Original paper
Clinical efficacy and safety of oral versus subcutaneous administration of methotrexate in patients with rheumatoid arthritis

Objective: Comparison of the clinical efficacy and safety of oral versus subcutaneous (SC) administration of methotrexate (MTX) in patients with rheumatoid arthritis (RA).
Material and methods: MTX-naive patients with active RA (minimum 4 tender and minimum 3 swollen joints, DAS 28 >4) were eligible for the study. Sixty patients (53 females, 7 men) with established diagnosis of RA aged 20-78 years entered the study. The patients received 15 mg/week of MTX either orally (30 patients) or SC (30 patients) for 24 weeks. At week 16, in patients who did not meet improvement (minimum 0.6 DAS 28 reduction) the dose of MTX was increased to 20 mg for the remaining 8 weeks. Prior to the study and at weeks 4, 8, 16 and 24 disease activity (DAS 28, number of tender and swollen joints, duration of morning stiffness, physician’s and patient’s global assessment of disease activity, erythrocyte sedimentation rate, CRP), quality of life, peripheral blood morphology, liver and kidney function were assessed. The occurrence of adverse events was noted.
Results: After 6 months 4 patients stopped oral MTX therapy (2 because of adverse events and 2 for other reasons) and 4 stopped SC MTX therapy (3 because of adverse events and 1 for other reasons). Adverse events were observed in 66% treated with MTX administered SC and in 71% treated with MTX administered orally. There was a greater frequency of gastrointestinal symptoms in patients with oral administration of MTX (47/24%). Good response (DAS 28 reduction >1.2) at week 24 was achieved in 69% of patients treated with SC MTX and in 42% with oral MTX, and moderate response (DAS 28 reduction by 0.6-1.2) in 16% and 19% accordingly.
Conclusions: There were minor gastrointestinal side effects in patients treated with MTX administered SC. SC administration was more effective than oral administration of the same dose of MTX.