Systematic Review Of Effects And Safety Of Filgotinib In Treatment Of Rheumatoid Arthritis

Objective:To evaluate the efficacy and safety of Filgotinib in the treatment of rheumatoid arthritis（RA）.Methods:We researched Pubmed,Embase,Cochrane,Wanfang Digital knowledge Service platform,China knowledge Network and CBMdisc（up to April 2021）for the randomized controlled trial（RCTs）investigating Filgotinib in the treatment of RA.The subjects were RA patients.The primary outcome measures were American College of Rheumatology（ACR）20,ACR 50 and ACR 70.The secondary outcomes were the disability index of the health questionnaire disability index（HAQ-DI）,low disease activity and clinical remission judged according to 28 joint disease activity score based on C-reactive protein（CRP）（DAS28-CRP）,the medical outcomes study（MOS）36-item short-form health survey.Two reviewers independently determined the inclusion of the trials and extracted the relevant data,evaluated the bias risk and analyzed the data,using Review Manager software（version 5.3）.For binary variable data,the effect size was relative risk（RR）and 95%confidence interval（CI）.For the data of continuous variables,the mean difference（MD）and 95%CI was used.Results:Six documents were included in this study,involving a total of 4247 patients.The included comparisons included Filgotinib versus placebo and Filgotinib versus other active agents.Seven RCTs compared Filgotinib with placebo,one RCT compared Filgointib with methotrexate（MTX）,and another RCT compared Filgotinib with adamumab（ADA）.Those RCTs comparing Filgotinib with placebo treated RA patients who with suboptimal resonse to conventional synthetic of disease-modifying antirheumatic drugs（cs DMARDs）.The meta analysis showed a significant advantage in primary outcomes ACR20,50 and 70 at 4 weeks,and the RRs（95%CI）were 1.66（1.50,1.84）,2.95（1.45,5.98）and 4.59（2.56,8.23）,respectively.This advantage was maintained till 24 weeks.Subgroup analysis showed that both 200 mg/d and 100 mg/d Filgotinib had significant advantages over placebo.The Filgotinib group was also significantly better than the placebo group in secondary outcomes HAQ-DI,low disease activity and clinical remission and SF-36.There was no significant difference in adverse events and withdrawal from the trial due to adverse reactions between these two groups.For the active RA patients who were naive to MTX therapy,one RCT（n=626）compared Filgotinib with MTX.In the primary outcomes,the RRs of ACR20/50/70 at 24^thweek were 1.09（1.00,1.20）,1.26（1.08,1.48）and 1.54（1.22,1.94）,respectively.At the 52nd week,the RRs were 1.21（1.09,1.35）,1.00（0.88,1.14）and 1.52（1.23,1.87）respectively.Filgotinib was superior to MTX in the secondary outcomes such as HAQ-DI,clinical remission and SF-36.There was no significant difference in adverse reaction events and withdrawal due to adverse reactions between these two groups.One RCT（n=1280）compared Filgotinib with ADA in RA patients with suboptimal respond to MTX.In terms of the primary outcomes,the RRs of ACR20,ACR50,and ACR70 at 12 weeks were 1.04（0.96,1.13）,1.59（1.01,1.41）and 1.54（1.16,2.09）,respecively.At 24 weeks,the RRs were 1.04（0.97,1.12）,1.06（0.94,1.20）and 1.11（0.92,1.35）,respectively.There were no significant differences between these two groups in adverse events and withdrawal from the trial due to adverse reactions.Conclusion:Filgotinib was superior to placebo in the treatment of RA with suboptimal response to cs DMARDs and there was no significant difference in safety outcomes between Filgotinib and placebo.These results show that Filgotinib may be an important choice for RA patients with suboptimal response to cs DMARDs.For active RA patients who were naive to MTX,Filgotinib had no obvious advantage compared with MTX in the primary outcomes and therefore should not replace MTX to become a first-line RA treatment.Limited data suggested that the efficacy of Filgotinib and ADA for RA patients with suboptimal cs DMARDs response was similar in terms of primary outcomes.