Connecticut Children's Medical Center, Hartford, CT, USA.
Gastroenterology. 2012 Aug;143(2):365-74.e2. doi: 10.1053/j.gastro.2012.04.046. Epub 2012 May 2.
BACKGROUND & AIMS: The IMAgINE 1 study (NCT00409682) evaluated the safety and efficacy of adalimumab double-blind maintenance dosing regimens following open-label induction for pediatric patients with moderate to severe Crohn's disease (CD).
We studied 192 patients with Pediatric Crohn's Disease Activity Index (PCDAI) scores >30 for whom conventional treatment was unsuccessful. Patients received open-label induction therapy with subcutaneous adalimumab at weeks 0 and 2 (160 mg and 80 mg, or 80 mg and 40 mg, for body weight ≥40 kg or <40 kg). At week 4, 188 patients were assigned to groups based on achievement of clinical response (defined as decrease in PCDAI ≥15 points from baseline; 155/188 [82.4%]) and prior exposure to infliximab (82/188 [43.6%]). Groups were given double-blind maintenance therapy with adalimumab at high (40 mg or 20 mg for body weight ≥40 kg or <40 kg; n = 93) or low doses (20 mg or 10 mg for body weight ≥40 kg or <40 kg; n = 95) every other week for 48 weeks. Clinical remission (PCDAI ≤10) at week 26 (the primary end point) was compared between groups using the Cochran-Mantel-Haenszel test, adjusting for strata, with nonresponder imputation. Adverse events were monitored to evaluate safety.
A total of 152 of 188 patients (80.9%) completed all 26 weeks of the study. At week 26, 63 patients (33.5%) were in clinical remission, with no significant difference between high- and low-dose groups (36/93 [38.7%] vs 27/95 [28.4%]; P = .075). No new safety signals were detected.
Adalimumab induced and maintained clinical remission of children with CD, with a safety profile comparable to that of adult patients with CD. More children who received high compared with low dose were in remission at week 26, but the difference between dose groups was not statistically significant.
IMA gINE 1 研究(NCT00409682)评估了阿达木单抗在中度至重度克罗恩病(CD)儿科患者接受开放标签诱导治疗后的双盲维持剂量方案的安全性和疗效。
我们研究了 192 名 PCDAI 评分>30 的患有小儿克罗恩病活动指数(PCDAI)的患者,这些患者对常规治疗无效。患者接受皮下阿达木单抗的开放标签诱导治疗,剂量分别为第 0 周和第 2 周的 160 mg 和 80 mg(体重≥40 kg 者)或 80 mg 和 40 mg(体重<40 kg 者)。第 4 周,根据临床应答(定义为 PCDAI 较基线下降≥15 分)和先前接受英夫利昔单抗治疗(82/188 [43.6%]),188 名患者被分为两组。两组患者接受阿达木单抗双盲维持治疗,剂量分别为高剂量(体重≥40 kg 者为 40 mg 或 20 mg,体重<40 kg 者为 20 mg 或 10 mg)或低剂量(体重≥40 kg 者为 20 mg 或 10 mg,体重<40 kg 者为 10 mg 或 5 mg),每两周一次,持续 48 周。使用 Cochran-Mantel-Haenszel 检验比较两组患者在第 26 周(主要终点)时的临床缓解率(PCDAI≤10),调整分层因素,并进行无应答者插补。监测不良反应以评估安全性。
188 名患者中共有 152 名(80.9%)完成了全部 26 周的研究。第 26 周时,63 名患者(33.5%)达到临床缓解,高剂量组与低剂量组之间无显著差异(36/93 [38.7%] vs 27/95 [28.4%];P=.075)。未发现新的安全性信号。
阿达木单抗诱导并维持 CD 患儿的临床缓解,安全性与 CD 成年患者相当。与接受低剂量相比,接受高剂量的患儿在第 26 周时缓解的比例更高,但两组之间的差异无统计学意义。