Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: The CHARM trial
Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: The CHARM trial
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DOI：
10.1053/j.gastro.2006.11.041
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发表时间：
2007-01-01
期刊：
影响因子：
29.4
通讯作者：
Pollack, Paul F.
中科院分区：
文献类型：
--
作者：
Colombel, Jean-Frederic;Sandborn, William J.;Pollack, Paul F.
背景和目标：本研究评价了阿达木单抗（一种全人源抗肿瘤坏死因子单克隆抗体）皮下给药在中重度克罗恩病（CD）患者中维持应答和缓解的疗效和安全性。方法：患者接受阿达木单抗80 mg（第0周）和40 mg（第2周）的开放标签诱导治疗。第4周时，患者按缓解（克罗恩病活动指数较基线降低70分）分层，并随机接受安慰剂、阿达木单抗40 mg每隔一周（eow）或阿达木单抗40 mg每周一次双盲治疗，直至第56周。共同主要终点是在第26周和第56周达到临床缓解（克罗恩病活动指数评分< 150）的随机应答者的百分比。结果如下：阿达木单抗40 mg eow组和40 mg每周一次组在第26周（分别为40%、47%和17%; P <0.001）和第56周（分别为36%、41%和12%; P <0.001）时缓解的随机应答者百分比显著高于安慰剂组。未观察到阿达木单抗eow和每周一次之间的疗效存在显著差异。安慰剂组因不良事件而终止治疗的患者（13.4%）多于阿达木单抗组（40 mg eow组和40 mg每周一次组分别为6.9%和4.7%）。结论：在对阿达木单抗有应答的患者中，阿达木单抗eow和每周一次在维持中重度CD缓解至56周方面均显著优于安慰剂。阿达木单抗耐受性良好，安全性特征与既往用药经验一致。
Background & Aims: This study evaluated the efficacy and safety of adalimumab, a fully human, anti-tumor necrosis factor monoclonal antibody administered subcutaneously, in the maintenance of response and remission in patients with moderate to severe Crohn's disease (CD). Methods: Patients received open-label induction therapy with adalimumab 80 mg (week 0) followed by 40 mg (week 2). At week 4, patients were stratified by response (decrease in Crohn's Disease Activity Index 70 points from baseline) and randomized to double-blind treatment with placebo, adalimumab 40 mg every other week (eow), or adalimumab 40 mg weekly through week 56. Coprimary end points were the percentages of randomized responders who achieved clinical remission (Crohn's Disease Activity Index score < 150) at weeks 26 and 56. Results: The percentage of randomized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 (40%, 47%, and 17%, respectively; P < .001) and week 56 (36%, 41%, and 12%, respectively; P < .001). No significant differences in efficacy between adalimumab eow and weekly were observed. More patients receiving placebo discontinued treatment because of an adverse event (13.4%) than those receiving adalimumab (6.9% and 4.7% in the 40-mg eow and 40-mg weekly groups, respectively). Conclusions: Among patients who responded to adalimumab, both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks. Adalimumab was well-tolerated, with a safety profile consistent with previous experience with the drug.