Sirukumab in rheumatoid arthritis refractory to sulfasalazine or methotrexate: a randomized phase 3 safety and efficacy study in Japanese patients

被引：17

作者：

Takeuchi, Tsutomu ^{[1
]}

Yamanaka, Hisashi ^{[2
]}

Harigai, Masayoshi ^{[2
]}

Tamamura, Ryo ^{[3
]}

Kato, Yuichi ^{[3
]}

Ukyo, Yoshifumi ^{[3
]}

Nakano, Toshikazu ^{[3
]}

Hsu, Benjamin ^{[4
]}

Tanaka, Yoshiya ^{[5
]}

机构：

[1] Keio Univ, Sch Med, Shinjuku Ku, Tokyo, Japan

[2] Tokyo Womens Med Univ, Shinjuku Ku, Tokyo, Japan

[3] Janssen Pharmaceut KK, Chiyoda Ku, Tokyo, Japan

[4] Janssen Res & Dev LLC, Spring House, PA 19477 USA

[5] Univ Occupat & Environm Hlth Japan, Kitakyushu, Fukuoka, Japan

来源：

ARTHRITIS RESEARCH & THERAPY | 2018年 / 20卷

关键词：

Biologicals; Disease-modifying anti-rheumatic drugs; Interleukin-6; Rheumatoid arthritis; Sirukumab; MODIFYING ANTIRHEUMATIC DRUGS; DOUBLE-BLIND; INADEQUATE RESPONSE; MONOCLONAL-ANTIBODY; INTRAVENOUS TOCILIZUMAB; PARALLEL-GROUP; THERAPY; TRIAL; MONOTHERAPY; MODERATE;

D O I：

10.1186/s13075-018-1536-9

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Sirukumab, a high-affinity human monoclonal antibody that selectively binds to interleukin-6, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) in global phase 1 and phase 2 studies. The present study evaluated the safety and efficacy of sirukumab, as monotherapy in Japanese patients with RA refractory to methotrexate or sulfasalazine. Methods: In this phase 3, double-blind study, 122 patients (age >= 20 years) were randomized (1: 1, 61 patients in each arm) to sirukumab administered subcutaneously: 50 mg once every 4 weeks (q4w) or 100 mg once every 2 weeks (q2w) through 52 weeks. Disease-modifying anti-rheumatic drugs were allowed after 24 weeks. Safety was assessed and efficacy was evaluated using American College of Rheumatology (ACR) responses, Disease Activity Score C-reactive protein (DAS28-CRP) and Health Assessment Questionnaire-Disability Index (HAQ-DI). Results: Amongst the 122 randomized patients, 99 (81.1%) patients completed the study. Adverse events (AEs) were reported in 114/122 (93.4%) patients and serious AEs were reported in 9/122 (7.4%) patients. No deaths, major cardiovascular AEs, serious gastrointestinal perforations or tuberculosis cases were reported during this study period. Grade 3 hematologic abnormalities (neutropenia and leukopenia) were reported in seven patients and no grade 4 abnormalities were observed. ACR20 responses were observed within 2 weeks, achieved in 47/61 (77.0%, 50 mg q4w) patients and 44/61 (72.1%, 100 mg q2w) patients at week 16 and maintained through week 52. ACR50/70, DAS28-CRP and HAQ-DI responses were also maintained through week 52 in both groups. Conclusions: Safety findings were comparable between the two treatment groups. The 52-week administration of sirukumab at 50 mg q4w and 100 mg q2w was generally tolerable and with measurable efficacy in Japanese patients with RA refractory to methotrexate and sulfasalazine.

引用

页数：11

共 20 条

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