AB0493 THE EFFICACY AND SAFETY OF TOFACITINIB IN THE TREATMENT OF DMARDS NAIVE RHEUMATOID ARTHRITIS PATIENTS (EASTERN STUDY)

Background Janus kinase (JAK) inhibitor is a great addition to the therapeutic options for rheumatoid arthritis (RA). However, the the clinical efficacy and safety of tofacitinib comparing with methotrexate (MTX) was not elucidated. Objectives We conducted a controlled randomized clinical trial in treatment naive rheumatoid arthritis (RA) patients to explore the clinical efficacy and safety of tofacitinib (TOFA) comparing with MTX. Methods In this open-label, randomized, and controlled clinical trial, treatment naive RA patients at the status of medium or high disease activity [simplified disease activity index (SDAI)>3.3] were randomized at 1:1 ratio into TOFA and MTX groups. Patients in TOFA group received tofacitinib 5 mg twice per day and patients in MTX group received MTX 10-15 mg once per week plus betamethasone 1ml muscle injection at enrollment. The rate of disease activity improvement (defined as SDAI decreased >50% against baseline or at least 10) at week 12 was taken as primary outcome. Patients who did not achieve improvement transferred to the other group. Secondary outcomes included the rates of remission, low disease activity (LDA) and change of disease activity scores. Results 100 patients were enrolled in the study with 49 in TOFA group and 51 in MTX group. The improvement rate was much higher in TOFA group than in MTX group [29.3% (12/41) vs 7.5% (3/40), p=0.025]. The rate of remission and low disease activity at week 4 and week 12 were comparable between the two groups. The change of SDAI [17.9 (7.3-30.3) vs 10.8 (5.5-17.4), p=0.062], CDAI [7 (4.8-16) vs 15 (7.5-26), p=0.011], DAS28-CRP [2.1 (1.2-3.4) vs 1.4 (0.7-2.1), p=0.010] and DAS28-ESR [3.8 (2.5-5.2) vs 2.7 (1.8-3.9), p=0.005] at week 12 were all more significant in TOFA group than in MTX group. The total adverse event rate was high in MTX group than in TOFA group [28% (14/50) vs % (4/49), p=0.022]. Considering specific adverse events, the rates of liver damage [16% (8/50) vs 0, p=0.001] and dizzy [6% (3/50) vs 0, p=0.041] were higher in MTX group than in TOFA group. Conclusion For treatment naive RA patients, tofacitinib can bring higher rate of improvement of disease activity. References [1]Smolen JS, Landewé RBM, Bijlsma JWJ, Burmester GR, Dougados M, Kerschbaumer A, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis. 2020;79(6):685-99. [2]Li Z, An Y, Su H, Li X, Xu J, Zheng Y, et al. Tofacitinib with conventional synthetic disease-modifying antirheumatic drugs in Chinese patients with rheumatoid arthritis: Patient-reported outcomes from a Phase 3 randomized controlled trial. Int J Rheum Dis. 2018;21(2):402-14. [3]Burmester GR, Blanco R, Charles-Schoeman C, Wollenhaupt J, Zerbini C, Benda B, et al. Tofacitinib (CP-690,550) in combination with methotrexate in patients with active rheumatoid arthritis with an inadequate response to tumour necrosis factor inhibitors: a randomised phase 3 trial. Lancet. 2013;381(9865):451-60. [4]Cohen SB, Pope J, Haraoui B, Irazoque-Palazuelos F, Korkosz M, Diehl A, et al. Methotrexate withdrawal in patients with rheumatoid arthritis who achieve low disease activity with tofacitinib modified-release 11 mg once daily plus methotrexate (ORAL Shift): a randomised, phase 3b/4, non-inferiority trial. The Lancet Rheumatology. 2019;1(1):e23-e34. [5]Fleischmann R, Mease PJ, Schwartzman S, Hwang LJ, Soma K, Connell CA, et al. Efficacy of tofacitinib in patients with rheumatoid arthritis stratified by background methotrexate dose group. Clin Rheumatol. 2017;36(1):15-24. [6]Fleischmann R, Mysler E, Hall S, Kivitz AJ, Moots RJ, Luo Z, et al. Efficacy and safety of tofacitinib monotherapy, tofacitinib with methotrexate, and adalimumab with methotrexate in patients with rheumatoid arthritis (ORAL Strategy): a phase 3b/4, double-blind, head-to-head, randomised controlled trial. Lancet. 2017;390(10093):457-68. Acknowledgements The Statistical Office of Peking University First Hospital was appreciated. We acknowledged Fangfang Fan and Xueying Li for the assistance in statistics. We acknowledged Yuhang Liu, Xiaojun Meng for the physical examination, disease activity evaluation and administration of subjects. Disclosure of Interests None Declared.