Center for Advanced IBD Research and Treatment, Kitasato Institute Hospital, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8462, Japan.
Janssen Pharmaceutical K.K., Tokyo, Japan.
J Gastroenterol. 2017 Oct;52(10):1101-1111. doi: 10.1007/s00535-017-1326-1. Epub 2017 Mar 21.
The global phase 3 studies of golimumab [PURSUIT-SC and PURSUIT-maintenance (M)], an anti-tumor necrosis factor-α (anti-TNFα) antibody, have demonstrated clinical efficacy and safety as induction and maintenance therapies in patients with moderate to severely active ulcerative colitis (UC). This study aimed to evaluate the efficacy and safety of golimumab as maintenance therapy in the Japanese population.
In this phase 3, double-blind (DB), placebo-controlled, parallel group, randomized withdrawal study, 144 Japanese patients with moderately to severely active UC received golimumab doses of 200 mg (at week 0) and 100 mg (at week 2) subcutaneously during the 6-week open-label induction phase. Patients who responded to golimumab induction therapy entered the DB maintenance (M) phase and were randomized (1:1) to receive 100 mg of golimumab subcutaneous injection (SC) or placebo every 4 weeks for 52 weeks. The primary endpoint was clinical response through M-week 54; secondary endpoints included clinical remission and mucosal healing at M-week 30 and 54.
Among induction responders, more patients on golimumab treatment (56.3%) maintained clinical response through M-week 54 versus the placebo group (19.4%). At both M-week 30 and 54, 50% golimumab-treated patients achieved clinical remission versus the placebo group (6.5%) and a higher proportion of patients on golimumab (59.4%) experienced mucosal healing than the placebo group (16.1%). Incidence of treatment-emergent adverse events was 96.9% in the golimumab group and 71% in the placebo group. Overall, the efficacy and safety results in this study were comparable with those observed in global studies.
Golimumab SC treatment maintained clinical efficacy through week 54 among induction responders, and no new safety signals were observed in the patients with moderate to severely active UC.
The study is registered at ClinicalTrials.gov NCT01863771.
抗肿瘤坏死因子-α（anti-TNFα）抗体戈利木单抗[PURSUIT-SC 和 PURSUIT-维持（M）]的全球 3 期研究已证实其在中重度活动溃疡性结肠炎（UC）患者中的诱导和维持治疗的临床疗效和安全性。本研究旨在评估戈利木单抗作为维持治疗在日本人群中的疗效和安全性。
在这项 3 期、双盲（DB）、安慰剂对照、平行组、随机撤药研究中，144 例中重度 UC 日本患者接受戈利木单抗 200mg（第 0 周）和 100mg（第 2 周）皮下注射，为期 6 周的开放性诱导期。对戈利木单抗诱导治疗有反应的患者进入 DB 维持（M）期，并随机（1:1）接受戈利木单抗 100mg 皮下注射（SC）或安慰剂，每 4 周 1 次，共 52 周。主要终点是 M 治疗第 54 周的临床应答；次要终点包括 M 治疗第 30 周和第 54 周的临床缓解和黏膜愈合。
在诱导应答者中，更多接受戈利木单抗治疗的患者（56.3%）在 M 治疗第 54 周时维持临床应答，而安慰剂组为 19.4%。在 M 治疗第 30 周和第 54 周时，50%接受戈利木单抗治疗的患者达到临床缓解，而安慰剂组为 6.5%，更多接受戈利木单抗治疗的患者（59.4%）实现黏膜愈合，而安慰剂组为 16.1%。戈利木单抗组的治疗出现不良事件发生率为 96.9%，安慰剂组为 71%。总体而言，这项研究中的疗效和安全性结果与全球研究观察到的结果一致。
在诱导应答者中，戈利木单抗 SC 治疗可维持至 M 治疗第 54 周，且在中重度 UC 患者中未观察到新的安全性信号。
该研究在 ClinicalTrials.gov 注册，编号为 NCT01863771。
