title: A randomized, double-blind, and placebo-controlled multicenter clinical trial of a novel cytotoxic T-lymphocyte antigen-4 fusion protein, Leining, in Chinese active rheumatoid arthritis patients with an inadequate response to methotrexate.
abstract: To assess the clinical efficacy as well as safety profiles of Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein, versus placebo in the treatment of Chinese active rheumatoid arthritis (RA) patients with an inadequate clinical response to methotrexate (MTX). In this 24-week, randomized, double-blind, placebo-controlled multicenter study, a total of 440 Chinese patients with active RA with an inadequate response to MTX were randomly assigned to receive Leining (10 mg/kg) or placebo. Clinical response was assessed using the American College of Rheumatology 20 % improvement criteria ACR20, ACR50, and ACR70, with ACR20 as the primary major endpoints. Disease activity scores in 28 joints with erythrocyte sedimentation rate assessment (DAS28-ESR) were used to evaluate disease activity. After 24 weeks of treatment, significantly more patients in Leining group achieved ACR20 response than those in placebo group (70.61 vs. 46.36 %; p < 0.001). Similarly, ACR50 and ACR70 responses of Leining group were significantly higher than those of placebo group (40.30 vs. 22.73 %; p < 0.001 and 16.67 vs. 7.27 %; p < 0.05, respectively). DAS28-ESR in Leining group was significantly reduced compared to that in placebo group, with greater clinically meaningful (>1.2 unit) improvement (54.85 vs. 29.09 %, p < 0.05). Both the rates of remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR < 3.2) were greater in the Leining group than those in the placebo group (12.42 vs. 2.73 %; p < 0.05 and 15.45 vs. 2.73 %; p < 0.05 respectively). The overall incidence of adverse events was similar in both Leining and placebo groups. No neutralizing antibodies were detected. Leining demonstrated clinically meaningful efficacy compared with placebo in Chinese patients with active RA despite MTX therapy. Administration of Leining in combination with MTX for 24 weeks was well tolerated.
authors.affiliation: Department of Rheumatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 145 Middle Shandong Road, Shanghai, 200001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.forename: Dong-bao
authors.initials: DB
authors.lastname: Zhao
authors.forename: Shao-xian
authors.initials: SX
authors.lastname: Hu
authors.forename: Hu-ji
authors.initials: HJ
authors.lastname: Xu
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Miu-jia
authors.initials: MJ
authors.lastname: Zhang
authors.forename: Zhi-wei
authors.initials: ZW
authors.lastname: Chen
authors.forename: Feng-xiao
authors.initials: FX
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.forename: Xin-fu
authors.initials: XF
authors.lastname: Li
authors.forename: Li-Qi
authors.initials: LQ
authors.lastname: Bi
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Chun-de
authors.initials: CD
authors.lastname: Bao
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000276:immunology; D044466:Asian People; D001799:Blood Sedimentation; D002681:China / Q000453:epidemiology; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012074:Remission Induction; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; C000599049:leining fusion protein; D008727:Methotrexate