Sandborn William J, Rutgeerts Paul, Enns Robert, Hanauer Stephen B, Colombel Jean-Frédéric, Panaccione Remo, D'Haens Geert, Li Ju, Rosenfeld Marie R, Kent Jeffrey D, Pollack Paul F
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Ann Intern Med. 2007 Jun 19;146(12):829-38. doi: 10.7326/0003-4819-146-12-200706190-00159. Epub 2007 Apr 30.
Adalimumab, a fully human tumor necrosis factor (TNF) antagonist, is an effective treatment for patients with Crohn disease who are naive to the chimeric TNF antagonist, infliximab. No anti-TNF agent has been evaluated prospectively in patients with Crohn disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent.
To determine whether adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who have symptoms despite infliximab therapy or who cannot take infliximab because of adverse events.
4-week, randomized, double-blind, placebo-controlled trial (November 2004 to December 2005).
52 sites in the United States, Canada, and Europe.
325 adults 18 to 75 years of age who had a history of Crohn disease for 4 months or more that was moderate to severe at baseline (Crohn's Disease Activity Index [CDAI] score, 220 to 450 points).
Patients were randomly assigned to receive induction doses of adalimumab, 160 mg and 80 mg, at weeks 0 and 2, respectively, or placebo at the same time points.
The primary end point was induction of remission at week 4. Decreases in CDAI score by 70 or more and 100 or more points (secondary end points) were also measured.
A total of 301 patients completed the trial. Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P < 0.001). The absolute difference in clinical remission rates was 14.2 percentage points (95% CI, 6.7 to 21.6 percentage points). A 70-point response occurred at week 4 in 52% (82 of 159) of patients in the adalimumab group versus 34% (56 of 166) of patients in the placebo group (P = 0.001). The absolute difference in 70-point response rates was 17.8 percentage points (CI, 7.3 to 28.4 percentage points). Two of 159 patients in the adalimumab group and 4 of 166 patients in the placebo group discontinued treatment because of adverse events. No patients in the adalimumab group and 4 of 166 patients in the placebo group had a serious infection.
The trial did not directly compare alternative active treatments and did not evaluate maintenance of response or long-term immunogenicity of adalimumab.
Adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who cannot tolerate infliximab or have symptoms despite receiving infliximab therapy. For more information on adalimumab in Crohn disease, click here. ClinicalTrials.gov registration number: NCT00105300.
阿达木单抗是一种全人源肿瘤坏死因子（TNF）拮抗剂，对于未使用过嵌合TNF拮抗剂英夫利昔单抗的克罗恩病患者是一种有效的治疗药物。对于曾对另一种抗TNF药物有反应但后来失去反应或不耐受该药物的克罗恩病患者，尚无抗TNF药物进行过前瞻性评估。
确定在尽管接受英夫利昔单抗治疗仍有症状或因不良事件而不能使用英夫利昔单抗的成年克罗恩病患者中，阿达木单抗诱导缓解的频率是否高于安慰剂。
为期4周的随机、双盲、安慰剂对照试验（2004年11月至2005年12月）。
美国、加拿大和欧洲的52个研究点。
325名年龄在18至75岁之间的成年人，有4个月或更长时间的克罗恩病病史，基线时病情为中度至重度（克罗恩病活动指数[CDAI]评分220至450分）。
患者被随机分配在第0周和第2周分别接受诱导剂量的阿达木单抗（160mg和80mg），或在相同时间点接受安慰剂。
主要终点是第4周时诱导缓解。还测量了CDAI评分降低70分或更多以及100分或更多（次要终点）。
共有301名患者完成试验。阿达木单抗组21%（159名中的34名）的患者在第4周实现缓解，而安慰剂组为7%（166名中的12名）（P<0.001）。临床缓解率的绝对差异为14.2个百分点（95%CI，6.7至21.6个百分点）。阿达木单抗组52%（159名中的82名）的患者在第4周出现70分的反应，而安慰剂组为34%（166名中的56名）（P = 0.001）。70分反应率的绝对差异为17.8个百分点（CI，7.3至28.4个百分点）。阿达木单抗组159名患者中有2名因不良事件停药，安慰剂组166名患者中有4名因不良事件停药。阿达木单抗组无患者发生严重感染，安慰剂组166名患者中有4名发生严重感染。
该试验未直接比较其他活性治疗方法，也未评估阿达木单抗的反应维持情况或长期免疫原性。
在不能耐受英夫利昔单抗或尽管接受英夫利昔单抗治疗仍有症状的成年克罗恩病患者中，阿达木单抗诱导缓解的频率高于安慰剂。有关阿达木单抗治疗克罗恩病的更多信息，请点击此处。ClinicalTrials.gov注册号：NCT00105300。
