Background Tofacitinib (TOFA) is so far the only representative of a new class of Jak-kinase inhibitors in rheumatology. Despite extensive data on TOFA obtained from 3rd phase studies, for use in clinical practice, the information is limited.
Objectives To study the efficacy and safety of TOFA in RA in clinical practice.
Methods We represent the combined data from two parallel IV Phase open-label observational clinical trials, modelling clinical practice, conducted by very similar protocols in 11 rheumatology centers in Russia. Inclusion criteria were active RA, methotrexate (MTX) failure, and/or other synthetic or biologic DMARDs failure. In total, 142 pts (26 males, 116 females, age 51,5±12,2 years, disease duration 88,6±78,1 months, 86,6% RF(+), 76,6% ACPA(+), 81,7% with erosive disease, DAS28-ESR 5,89±1,03, SDAI 35,7±13,4, HAQ 1,59±0,64) were included. 32 (22,5%) pts had biologics in history. TOFA used in the dose of 5 mg BID for 6 months, with possibility to increase to 10 mg BID (carried out in 27 pts after 11,3±2,7 weeks). 115 (81%) pts received TOFA in combination with MTX (18±4,5 mg per week), 18 with leflunomide or sulfasalazine, 9 pts used TOFA in monotherapy.
Results 129 (90,8%) pts successfully completed the six-month period of treatment. TOFA was withdrawn due to lack of response in 6 cases, adverse events (AEs) in 4 (pneumonia, arterial hypertension, skin vasculitis, mouth ulcers), withdrawal of informed consent – 2, protocol violation – 1. At month 3 SDAI score decreased to 14,6±10,9 (p<0,01), 55 (42,6%) pts achieved SDAI LDA and 22 (17,1%) SDAI remission; HAQ decreased to 0,95±0,61, HAQ≤0,5 observed in 36 (27,9%) pts. After 6 months, SDAI and HAQ scores decreased to 10,5±8,6 and 0,83±0,64 resp. (p<0,01); 81 (62,8%) pts achieved SDAI LDA and 29 (22,5%) SDAI remission; HAQ≤0,5 observed in 48 (37,2%) pts. Results of treatment in patients with and without biological DMARDs in history were similar. Pts who needed dose escalation of TOFA had worse results at month 3 compared to others (SDAI 21±10,2 and to 13,2±10,7 resp., p=0,02), but after increase of the dose to 10 mg BID at month 6 they showed a slightly better result (SDAI 9,5±7,1 and to 10,7±8,9 resp., p=0,54). Only 2 serious AEs (pneumonia and skin vasculitis) observed. We didn't see any case of Herpes zoster in our group.
Conclusions TOFA was effective in patients with severe RA who did not respond to both synthetic and biological DMARDs (achievement of SDAI LDA in 42,6% of pts at month 3 and in 62,8% at month 6). Dose escalation to 10 mg BID can be useful in ¼ of patients who do not respond to standard dose of TOFA. TOFA has shown a good safety profile.
Acknowledgements This scientific study was supported by grant by Pfizer.
Disclosure of Interest E. Luchikhina Grant/research support from: Pfizer, Biocad, Speakers bureau: Abbvie, Pfizer, Tirupharm, D. Karateev Grant/research support from: Pfizer, Consultant for: Pfizer, Tirupharm, Biocad, Egis, R-Pharm, Novartis, Speakers bureau: Abbvie, Bristol Myers Squibb, Pfizer, Roche, Tirupharm, Biocad, R-Pharm, Novartis, Egis, MSD, UCB, A. Misiyuk: None declared, N. Demidova: None declared, G. Loukina: None declared, D. Abdulganieva: None declared, A. Baranov: None declared, A. Babaeva: None declared, L. Evstigneeva: None declared, O. Ivanova: None declared, V. Mazurov: None declared, O. Semagina: None declared, A. Sizikov: None declared, V. Sorotskaya: None declared, E. Nasonov: None declared