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
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.
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页数:11
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