Adalimumab Induces and Maintains Mucosal Healing in Patients With Crohn's Disease: Data From the EXTEND Trial
Adalimumab Induces and Maintains Mucosal Healing in Patients With Crohn's Disease: Data From the EXTEND Trial
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DOI：
10.1053/j.gastro.2012.01.035
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发表时间：
2012-05-01
期刊：
影响因子：
29.4
通讯作者：
D'Haens, Geert
中科院分区：
文献类型：
--
作者：
Rutgeerts, Paul;Van Assche, Gert;D'Haens, Geert
背景与目的：我们研究了阿达木单抗诱导和维持克罗恩病（CD）患者粘膜愈合的疗效。方法：一项随机、双盲、安慰剂对照试验（通过内镜愈合扩展阿达木单抗的安全性和疗效[EXTEND]）在135例中重度回结肠CD成人患者中评价了阿达木单抗诱导和维持粘膜愈合的作用。通过回结肠镜检查记录粘膜溃疡的基线程度。所有患者均接受诱导治疗（第0/2周皮下注射阿达木单抗160/80 mg）。在第4周，患者被随机分配至阿达木单抗40 mg组或安慰剂组，每隔一周给药一次，直至第52周。从第8周开始，对发作或无应答的患者给予开放标签阿达木单抗。在第12周和第52周通过回结肠镜检查重新评估粘膜愈合。研究结果：阿达木单抗组27%的患者在第12周（主要终点）粘膜愈合，而安慰剂组为13%（P <0.056）。在第52周，粘膜愈合率分别为24%和0（P < .001）。根据克罗恩病内镜严重程度指数，阿达木单抗组第12周的缓解率为52%，安慰剂组为28%（P <0.006），第52周分别为28%和3%（P <0.001）。在第12周（47% vs 28%; P <0.021）和第52周（33% vs 9%; P <0.001），连续阿达木单抗治疗患者的克罗恩病活动指数临床缓解率高于安慰剂治疗患者。报告了5例严重感染（诱导期1例，开放标签治疗期4例）和3例机会性感染（双盲治疗期每组1例，开放标签治疗期1例）（n = 135）。结论：在阿达木单抗诱导治疗后，继续接受阿达木单抗治疗的中重度活动性CD患者比接受安慰剂治疗的患者更有可能实现粘膜愈合。
BACKGROUND & AIMS: We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn's disease (CD). METHODS: A randomized, double-blind, placebo-controlled trial (extend the safety and efficacy of adalimumab through endoscopic healing [EXTEND]) evaluated adalimumab for induction and maintenance of mucosal healing in 135 adults with moderate to severe ileocolonic CD. The baseline degree of mucosal ulceration was documented by ileocolonoscopy. All patients received induction therapy (subcutaneous adalimumab 160/80 mg at weeks 0/2). At week 4, patients were randomly assigned to groups given 40 mg adalimumab or placebo every other week through week 52. Open-label adalimumab was given to patients with flares or no response, starting at week 8. Mucosal healing was reassessed by ileocolonoscopy at weeks 12 and 52. RESULTS: Twenty-seven percent of patients receiving adalimumab had mucosal healing at week 12 (the primary end point) versus 13% given placebo (P < .056). At week 52, rates of mucosal healing were 24% and 0, respectively (P < .001). Remission rates, based on the Crohn's Disease Endoscopic Index of Severity, were 52% for adalimumab and 28% for placebo at week 12 (P < .006) and 28% and 3%, respectively, at week 52 (P < .001). Rates of clinical remission based on the Crohn's Disease Activity Index were greater among patients given continuous adalimumab therapy versus placebo at weeks 12 (47% vs 28%; P < .021) and 52 (33% vs 9%; P < .001). Five serious (1 during induction and 4 during open-label therapy) and 3 opportunistic infections (1 in each group during double-blind therapy and 1 during open-label therapy) were reported (n = 135). CONCLUSIONS: Following induction therapy with adalimumab, patients with moderately to severely active CD who continue to receive adalimumab are more likely to achieve mucosal healing than those given placebo.