Subcutaneous Golimumab Maintains Clinical Response in Patients With Moderate-to-Severe Ulcerative Colitis
Subcutaneous Golimumab Maintains Clinical Response in Patients With Moderate-to-Severe Ulcerative Colitis
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DOI：
10.1053/j.gastro.2013.06.010
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发表时间：
2014-01-01
期刊：
影响因子：
29.4
通讯作者：
Rutgeerts, Paul
中科院分区：
文献类型：
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作者：
Sandborn, William J.;Feagan, Brian G.;Rutgeerts, Paul
背景与目的：皮下注射抗肿瘤坏死因子-α(TNF-α)的全人单抗Golimumab被评价为维持治疗的方法，用于未使用肿瘤坏死因子-α拮抗剂的中重度活动期溃疡性结肠炎的成人，尽管常规治疗对Golimumab诱导治疗有反应。方法：我们对完成Golimumab诱导试验的患者进行了3期双盲试验(溃疡性结肠炎研究计划利用探索性治疗，例如，追踪)。对Golimumab诱导治疗有反应的患者(n=464)被随机分配到安慰剂组或在52周期间每4周注射50或100 mg Golimumab。在诱导研究中对安慰剂有反应的患者继续接受安慰剂治疗。诱导研究中的无应答者接受100 mg Golimumab治疗。主要终点是维持到54周的临床反应；次要终点包括30周和54周的临床缓解和粘膜愈合。结果：在接受50 mg Golimumab治疗的患者中，47.0%的患者在54周内保持临床反应，在接受100 mg Golimumab治疗的患者中，有49.7%的患者保持临床反应，在接受安慰剂治疗的患者中，有31.2%的患者保持了临床反应(分别为P-.010和P<；.001)。在第30周和第54周，接受100 mg Golimumab的患者临床缓解和粘膜愈合的比例(27.8%和42.4%)高于服用安慰剂的患者(分别为15.6%和26.6%；P=0.004和P=0.002)或50 mg Golimumab的患者(分别为23.2%和41.7%)。在服用安慰剂、50 mg和100 mg Golimumab的患者中，严重不良事件的比例分别为7.7%、8.4%和14.3%，严重感染的比例分别为1.9%、3.2%和3.2%。在研究中服用Golimumab的所有患者中，有3人死亡(均死于脓毒症、结核病和心力衰竭，均为服用100 mg Golimumab的患者)，4人发展为活动性结核病。结论：在用Golimumab诱导治疗有反应且有中至重度活动期溃疡性结肠炎的患者中，Golimumab(50 mg或100 mg)的临床反应维持到第54周；接受100 mg Golimumab的患者在30周和54周时临床缓解和粘膜愈合。在其他批准的适应症中，安全性与报道的其他肿瘤坏死因子α拮抗剂和Golimumab一致。
BACKGROUND & AIMS: Subcutaneous golimumab, a fully human monoclonal antibody to tumor necrosis factor-alpha (TNF alpha), was evaluated as maintenance therapy in TNF alpha antagonist-naive adults with moderate-to-severe active ulcerative colitis, despite conventional therapy, who responded to golimumab induction therapy. METHODS: We performed a phase 3, double-blind trial of patients who completed golimumab induction trials (Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment, eg, PURSUIT). Patients who responded to induction therapy with golimumab (n = 464) were assigned randomly to groups given placebo or injections of 50 or 100 mg golimumab every 4 weeks through week 52. Patients who responded to placebo in the induction study continued to receive placebo. Nonresponders in the induction study received 100 mg golimumab. The primary end point was clinical response maintained through week 54; secondary end points included clinical remission and mucosal healing at both weeks 30 and 54. RESULTS: Clinical response was maintained through week 54 in 47.0% of patients receiving 50 mg golimumab, 49.7% of patients receiving 100 mg golimumab, and 31.2% of patients receiving placebo (P - .010 and P < .001, respectively). At weeks 30 and 54, a higher percentage of patients who received 100 mg golimumab were in clinical remission and had mucosal healing (27.8% and 42.4%) than patients given placebo (15.6% and 26.6%; P - .004 and P = .002, respectively) or 50 mg golimumab (23.2% and 41.7%, respectively). Percentages of serious adverse events were 7.7%, 8.4%, and 14.3% among patients given placebo, 50 mg, or 100 mg golimumab, respectively; percentages of serious infections were 1.9%, 3.2%, and 3.2%, respectively. Among all patients given golimumab in the study, 3 died (from sepsis, tuberculosis, and cardiac failure, all in patients who received 100 mg golimumab) and 4 developed active tuberculosis. CONCLUSIONS: Golimumab (50 mg or 100 mg) maintained clinical response through week 54 in patients who responded to induction therapy with golimumab and had moderate-to-severe active ulcerative colitis; patients who received 100 mg golimumab had clinical remission and mucosal healing at weeks 30 and 54. Safety was consistent with that reported for other TNF alpha antagonists and golimumab in other approved indications.