Comparison of Two Adalimumab Treatment Schedule Strategies for Moderate-to-Severe Crohn's Disease: Results From the CHARM Trial
Comparison of Two Adalimumab Treatment Schedule Strategies for Moderate-to-Severe Crohn's Disease: Results From the CHARM Trial
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DOI：
10.1038/ajg.2009.59
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发表时间：
2009-05-01
影响因子：
9.8
通讯作者：
Mulani, Parvez M.
中科院分区：
文献类型：
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作者：
Colombel, Jean-Frederic;Sandborn, William J.;Mulani, Parvez M.
目的：比较诱导给药后连续阿达木单抗治疗与诱导给药后重新开始阿达木单抗治疗的结局（在临床恶化的情况下）用于参与完全人抗体阿达木单抗用于缓解维持的克罗恩试验（CHARM）的患有中度至重度克罗恩病（CD）的患者。在CHARM试验中，所有患者分别在第0周和第2周接受阿达木单抗80 mg和40 mg的开放标签诱导治疗。总共有778名患者在第4周被随机分配到三个组之一：（1）初始诱导剂量后的安慰剂（随后重新开始阿达木单抗治疗）;（2）阿达木单抗40 mg每隔一周（e.o.w.）的连续维持治疗;阿达木单抗40 mg/周持续维持治疗。在第12周时/之后，接受安慰剂治疗的复发或无应答患者可以重新开始开放标签阿达木单抗40 mg e.o.w.治疗，接受连续盲态阿达木单抗治疗的患者可转换为开放标签40 mg e.o.w.。所有组中的患者可转换为每周一次治疗，持续发作/无应答。在先前发表的主要分析中，仅分析了那些在第4周有应答（克罗恩病活动指数（CDAI）降低>= 70分，称为“随机应答者”）并仍接受盲法治疗的患者的结果。在这项分析中，所有随机化患者的数据均基于原始随机化治疗使用意向治疗分析进行分析，无论他们随后是否转为开放标签治疗。疾病活动，临床缓解，耀斑的数量，炎症性肠病问卷（IBDQ）评分，CD相关手术的数量，住院率之间进行了比较连续和诱导只/重新开始阿达木单抗group.RESULTS：结果所有的结果指标是上级为两个连续组相比，诱导只/重新开始组。基于中位CDAI和IBDQ结果，两个连续治疗组中的患者与仅诱导/重新开始组相比实现了统计学显著更大的改善（P < 0.05）。在第56周，接受连续阿达木单抗治疗的患者百分比显著更高（e.o.w.每周一次治疗组临床缓解率为49%，单纯诱导/再开始治疗组临床缓解率为38%（P < 0.05）。连续阿达木单抗治疗也与更少的发作和更少的CD相关手术相关（P < 0.05）。两个连续阿达木单抗治疗组患者CD相关和全因住院的风险均显著低于仅诱导治疗/重新开始治疗组患者（P < 0.05）。对于活动性CD患者，阿达木单抗连续治疗比诱导给药后在出现临床恶化时重新开始阿达木单抗治疗以维持临床缓解的策略更有效，改善生活质量，减少突发事件，减少手术次数和住院风险。
OBJECTIVES: To compare outcomes of induction dosing followed by continuous adalimumab treatment with those of induction dosing with reinitiation of adalimumab (in the event of clinical deterioration) for patients with moderate-to-severe Crohn's disease (CD) who participated in the Crohn's Trial of the Fully Human Antibody Adalimumab for Remission Maintenance (CHARM).METHODS: In the CHARM trial, all patients received open-label induction therapy with adalimumab 80 mg and 40 mg at weeks 0 and 2, respectively. In total, 778 patients were randomized at week 4 to one of three groups: (1) placebo after initial induction doses (followed by reinitiation of adalimumab therapy); (2) continuous maintenance treatment with adalimumab 40 mg every other week (e.o.w.); and (3) continuous maintenance treatment with adalimumab 40 mg every week. At/after week 12, patients receiving placebo with flare or non-response could reinitiate open-label adalimumab 40 mg e.o.w., and patients receiving continuous blinded adalimumab therapy could switch to open-label 40 mg e.o.w. Patients in all groups could switch to weekly therapy with continued flare/non-response. In the previously published primary analysis, results for only those patients who had responded at week 4 (decrease in Crohn's Disease Activity Index (CDAI) of >= 70 points, referred to as "randomized responders") and remained on blinded therapy were analyzed. In this analysis, data from all randomized patients were analyzed based on original randomized treatment using an intention-to-treat analysis, regardless of whether they subsequently switched to open-label therapy. Disease activity, clinical remission, number of flares, Inflammatory Bowel Disease Questionnaire (IBDQ) score, number of CD-related surgeries, and hospitalization incidence were compared between the continuous and induction only/reinitiation adalimumab groups.RESULTS: Results for all outcome measures were superior for both continuous groups compared with the induction only/reinitiation group. On the basis of median CDAI and IBDQ results, patients in both continuous treatment groups achieved statistically significantly greater improvements vs. the induction only/reinitiation group (P < 0.05). At week 56, a significantly greater percentage of patients who had received continuous adalimumab (51% for e.o.w. and 49% for weekly) were in clinical remission vs. the induction only/reinitiation group (38%, P < 0.05). Continuous adalimumab therapy was also associated with fewer flares and fewer CD-related surgeries (P < 0.05). Patients in both continuous adalimumab groups had significantly lower risks of CD-related and all-cause hospitalizations than did patients in the induction only/reinitiation group (P < 0.05).CONCLUSIONS: For patients with active CD, continuous treatment with adalimumab was more effective than a strategy of induction dosing followed by reinitiation of adalimumab with clinical deterioration for maintenance of clinical remission, improved quality-of life outcomes, reduced flares, and a decrease in number of surgeries and risk of hospitalization.