THU0188 Efficacy and safety of tofacitinib in patients with rheumatoid arthritis who did not respond to synthetic and biological dmards in clinical practice
Authors: EL Luchikhina, D Karateev, A Misiyuk, N Demidova, G Loukina, D Abdulganieva, A Baranov, A Babaeva, L Evstigneeva, O Ivanova, V Mazurov, O Semagina, A Sizikov, V Sorotskaya, E Nasonov
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> 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. <h3>Objectives</h3> To study the efficacy and safety of TOFA in RA in clinical practice. <h3>Methods</h3> 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. <h3>Results</h3> 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 TOFA was withdrawn due to lack of response in 6 cases, adverse events (AEs) in 4 (pneumonia, arterial hypertension, skin vasculitis, mouth ulcers), withdrawal of informed consent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&lt;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&lt;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 didn9t see any case of Herpes zoster in our group. <h3>Conclusions</h3> 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. <h3>Acknowledgements</h3> This scientific study was supported by grant by Pfizer. <h3>Disclosure of Interest</h3> 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