Применение тофацитиниба для лечения больных ревматоидным артритом, резистентных к синтетическим и биологическим базисным противовоспалительным препаратам, в реальной клинической практике ( результаты многоцентрового наблюдательного исследования)

Abstract

Tofacitinib (TOFA), a member of a new class of targeted synthetic disease-modifying antirheumatic drugs (DMARDs), is a promising medication for the treatment of rheumatoid arthritis (RA) and other immunoinflammatory diseases. The paper describes the Russian experi-ence with TOFA used to treat severe RA. Patients and methods. 101 RA patients (18 men and 83 women; mean age, 51.03±11.28 years; mean disease duration, 105.4±81.43 months) who were positive for rheumatoid factor (89.1%) and anti-cyclic citrullinated peptide antibodies (74.7%) and resistant to therapy with synthetic DMARDs (sDMARDs) (80.2%) and biological agents (19.8%) were given TOFA at a dose of 5 mg twice daily, which could be doubled if necessary. TOFA was used alone (n=9) or in combination with methotrexate (MT) (n=75) or other sDMARDs (n=17). The achievement of low disease activity (LDA) and clinical remission at 3 and 6 months of treatment by DAS28-ESR SDAI, and CDAI scores, and the indices of safety and tolerability were assessed. Results. A total of 93 (92.1%) of the 101 patients completed a 24-week period of the investigation. 8 (7.9%) patients prematurely discontinued TOFA after an average of 2.75±0.71 months. At the end of the study, the patients achieved the primary endpoint (LDA including remission) in terms of DAS28-ESR ≤3.2 (34.7%), SDAI ≤11 (47.5%), and CDAI ≤10 (48.5%) and the secondary endpoints (clinical remission) in terms of DAS28-ESR ≤2.6 (17.8%), SDAI ≤3.3 (8.9%), and CDAI ≤2.8 (6.9%). When TOFA was combined with MT, the discontinuation rate for the former was significantly lower (2.7%) than when TOFA was used in combination with other sDMARDs (29.4%) or alone (11.1%; p<0.01). At 3 and 6 months of follow-up, LDA was achieved more frequently when TOFA was combined with MT than when other treatment regimens were used. Fatal outcomes and serious adverse events (AEs), as AEs previously undescribed in the literature, were not seen during a follow-up within the framework of the clinical trial. Only 2 patients discontinued TOFA because of AEs. Conclusion. The use of TOFA in RA is effective in achieving LDA in patients unresponsive to sDMARDs and biological DMARDs. The prescription of the drug makes it possible to monitor the activity of the inflammatory process and, with its sufficient safety and good tolerability, to achieve LDA in half of the patients, including those with multidrug resistance.