Efficacy and safety of rapid dose escalation of methotrexate in rheumatoid arthritis. Results of the multicenter “METEOR” study

The aim of the study – to analyze the effectiveness and tolerability of subcutaneous methotrexate (sc MTX) (Metorthrit; S.C. Rompharm Company S.R.L) in patients with rheumatoid arthritis (RA) with high disease activity and rapid dose escalation, to assess their quality of life (QoL) in real clinical practice. Material and methods . The study included 105 patients, mostly women, with a reliable diagnosis of RA with high disease activity (DAS-28 (Disease Activity Score 28) ≥5.1) aged 18 years and older and ineffectiveness of previous oral MTX therapy for at least 6 months or who had not received MTX. Sc MTX therapy was started at a dose of 15 mg/weekly. During the first month of therapy, a rapid escalation of the sc MTX 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 (DAS-28 – from 5.8±0.75 to 2.93±1.05; CDAI (Clinical Disease Activity Score) – from 30.13±8.33 to 7.08±6.07; SDAI (Simplified Disease Activity Score) – from 32.78±9.64 to 7.48±6.53) and the activity index, which was evaluated by the patients themselves (RAPID-3 (Routine Assessment of Patient Index Data 3) from 16.18±4.6 to 5.56±4.66; p ≤0.05). The number of patients with high disease activity according to DAS-28 decreased by 2 times by the week 4 of therapy (to 46.2%), after 12 weeks they remained 13.3%, and by week 24 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 (Visual Analogue Score) ( p <0.001), which contributed to an improvement in the functional state: the HAQ (Health Assessment Questionnaire) index decreased on average from 1.47±0.65 to 0.64±052 points. Population indicators of functional status (HAQ≤0.5) by the week 24 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 week 24 of the study, 45% of patients had population-based indicators 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% and 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. Conclusion . 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 54.5%, to quickly improve the QoL, reduce the level of pain, reduce the dose of GC by 3 months of therapy or completely cancel them, reduce the need for NSAIDs by 7 times with an acceptable level of therapy safety.