Mayo Clinic, Rochester, Minnesota, USA.
Clin Gastroenterol Hepatol. 2010 Aug;8(8):688-695.e2. doi: 10.1016/j.cgh.2010.04.021. Epub 2010 May 6.
BACKGROUND & AIMS: Patients with moderate to severe Crohn's disease who receive infliximab may experience secondary failure (loss of response and/or hypersensitivity). Data on the utility of switching to certolizumab pegol in these patients are limited.
A total of 539 patients with active Crohn's disease and secondary failure to infliximab were enrolled in a 26-week trial. Patients received open-label induction with subcutaneous certolizumab pegol 400 mg at weeks 0, 2, and 4. Those in clinical response at week 6 were randomized to certolizumab pegol 400 mg every 2 or every 4 weeks through week 24. The primary end point was response at week 6. Secondary end points included remission at week 6 and response and remission at week 26.
At week 6, 334 of 539 patients (62.0%) achieved response and 212 of 539 (39.3%) achieved remission. A total of 329 patients were randomized and received maintenance therapy. At week 26, 39.9% (67 of 168) and 36.6% (59 of 161) of patients in the every-4-weeks and every-2-weeks groups were in clinical response, respectively (P = .55). Corresponding remission rates at week 26 were 29.2% and 30.4%, respectively (P = .81). Serious infections occurred in 9 of 539 (1.7%) and 12 of 373 (3.2%) of patients during induction and maintenance, respectively. A single malignancy (skin carcinoma) occurred in a patient receiving every-4-weeks maintenance therapy.
Response to open-label induction therapy with certolizumab pegol was achieved by 62% of patients with moderate to severely active Crohn's disease and secondary failure to infliximab. Among these patients, certolizumab pegol 400 mg every 4 weeks showed similar efficacy to every-2-weeks dosing for maintenance of response and remission.
接受英夫利昔单抗治疗的中重度克罗恩病患者可能会出现继发性失效（无应答和/或过敏）。关于这些患者改用培塞利珠单抗的效果的数据有限。
539 例活动性克罗恩病且对英夫利昔单抗继发性失效的患者参加了一项为期 26 周的试验。患者在第 0、2 和 4 周接受皮下注射培塞利珠单抗 400mg 的开放性诱导治疗。在第 6 周有临床应答的患者被随机分配至培塞利珠单抗 400mg 每 2 周或每 4 周治疗至第 24 周。主要终点为第 6 周的应答。次要终点包括第 6 周的缓解和第 26 周的应答和缓解。
第 6 周时，539 例患者中有 334 例（62.0%）达到应答，212 例（39.3%）达到缓解。共有 329 例患者接受了维持治疗。第 26 周时，每 4 周组和每 2 周组的患者分别有 39.9%（67/168）和 36.6%（59/161）达到临床应答（P=.55）。第 26 周时相应的缓解率分别为 29.2%和 30.4%（P=.81）。诱导和维持治疗期间，分别有 9 例（1.7%）和 12 例（3.2%）患者发生严重感染。接受每 4 周维持治疗的 1 例患者发生 1 例单一恶性肿瘤（皮肤癌）。
对英夫利昔单抗继发性失效的中重度活动性克罗恩病患者进行培塞利珠单抗开放性诱导治疗后，有 62%的患者达到应答。在这些患者中，培塞利珠单抗 400mg 每 4 周治疗与每 2 周治疗相比，在维持应答和缓解方面的疗效相似。
