Efficacy and Safety of Rapid Dose Escalation of Methotrexate in Rheumatoid Arthritis (Results of the Multicenter METEOR Study).

The aim of the study was to analyze the effectiveness and tolerability of subcutaneous methotrexate (sc MTX) (METHORTRIT; sc ROMPHARM Company) in RA patients with high disease activity with rapid dose escalation, to assess their quality of life (QOL) in real clinical practice. MATERIALS AND

methods-The study included 105 patients, mostly women, with a reliable diagnosis of RA with high disease activity (DAS28 ≥ 5.1) aged 18 years and older and ineffectiveness of previous oral MT therapy for at least 6 months or who had not received MT. sc MTX therapy was started at a dose of 15 mg /weekly. During the first month of therapy, a rapid escalation of the scMTX dose of 2.5 mg/week was performed once a week until the dose of 22.5 mg/week was reached; then, with insufficient response, the dose of sc MTX could be increased to 25 mg/week. The evaluation of the effectiveness of therapy, functional status, and QOL was carried out after 4-12-18-24 weeks.

results-After a rapid escalation of the sc MTX dose during the first month of the study, at all stages of follow-up, a rapid decrease in disease activity was noted for all standard indices (DAS28 from 5.8 ± 0.75 to 2.93 ± 1.05; CDAI from 30.13 ± 8.33 to 7.08 ± 6.07; SDAI from 32.78 ± 9.64 to 7.48 ± 6.53) and the activity index, which was evaluated by the patients themselves (RAPID-3 from 16.18 ± 4.6 to 5.56 ± 4.66), p ≤ 0.05. The number of patients with high disease activity according to DAS28 decreased by 2 times by the 4th week of therapy (to 46.2%), after 12 weeks they remained 13.3%, and by 24 weeks high activity remained only in 4.4% of patients. There was a marked decrease in pain from 65.6 ± 13.07 to 20.5 ± 17.1 mm in VAS (p < 0.001), which contributed to an improvement in the functional state: the HAQ index decreased on average from 1.47 ± 0.65 to 0.64 ± 052 points. Population indices of functional status (HAQ ≤ 0.5) by the 24th week of therapy were observed in 48.9% of patients. A decrease in the level of fatigue (from 6.25 ± 7.04 to 1.81 ± 1.71 cm according to VAS, p < 0.001) was accompanied by a decrease in anxiety (from 7.47 ± 4.03 to 2.36 ± 2.72, p < 0.001) and depression (from 7.77 ± 3.84 to 2.50 ± 2.56, p < 0.001), as well as improved sleep. By the 24th week of the study, 45% of patients had population-based indices of QOL according to the EQ-5D index. Glucocorticoids (GC) were completely eliminated in 2/3 of the patients. Patients who did not receive GC had lower disease activity by 24 weeks in all indices: DAS 28 (2.7 ± 0.1 and 3.4± 0.2, respectively), CDAI (6.0 ± 0.3 and 10.2 ± 0.1), SDAI (6.4 ± 0.2 and 10.9 ± 0.3), p < 0.05. Patients receiving and not receiving GC had the same number of adverse reactions (p > 0.05); however, the number of infections in patients receiving GC was significantly higher (9.5%-0.0, respectively, p = 0.009). The need for nonsteroidal anti-inflammatory drugs (NSAIDs) at the beginning of the study was in 93.2% of patients on average 21.1 days per month; after 24 weeks, the need for NSAIDs was in 54.4% of patients on average 3.8 days per month. In general, the safety profile of MTX was acceptable.

conclusions-With high RA activity, the tactics of starting therapy with sc MTX at a dose of 15 mg per week and a rapid escalation of its dose of 2.5 mg weekly to 22.5-25 mg/week, allows achieving therapy goals by 3 months in 17.8% of patients, and by 6 months in 64.5%, to quickly improve the QOL, reduce the level of pain, reduce the dose of GC by 3 months of therapy or completely cancel them, and reduce the need for NSAIDs by 7 times with an acceptable level of therapy safety.