Gastrointestinal Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4283, USA.
Clin Gastroenterol Hepatol. 2010 Jul;8(7):600-9. doi: 10.1016/j.cgh.2010.01.014. Epub 2010 Feb 1.
BACKGROUND & AIMS: The safety and efficacy of maintenance therapy with the anti-tumor necrosis factor certolizumab pegol has not been reported beyond 6 months. We assessed the long-term efficacy, safety, and immunogenicity of continuous versus interrupted maintenance therapy with subcutaneous certolizumab pegol in patients with Crohn's disease.
Patients who responded to induction therapy at week 6 of the PEGylated Antibody Fragment Evaluation in Crohn's Disease: Safety and Efficacy (PRECiSE) 2 trial were assigned randomly to groups given certolizumab pegol (continuous) or placebo (drug-interruption) during weeks 6 to 26. Patients who completed PRECiSE 2 were eligible to enter PRECiSE 3, an ongoing, prospective, open-label extension trial in which patients have received certolizumab pegol (400 mg) every 4 weeks for 54 weeks to date, and were not offered the option to increase their dose. Disease activity was measured by the Harvey-Bradshaw Index.
Harvey-Bradshaw Index responses at week 26 for the continuous and drug-interruption groups were 56.3% and 37.6%, respectively; corresponding remission rates were 47.9% and 32.4%, respectively. Of patients responding at week 26, response rates at week 80 after the start of PRECiSE 2 in the continuous and drug-interruption groups were 66.1% and 63.3%, respectively; among patients in remission at week 26, week 80 remission rates were 62.1% and 63.2%, respectively. More patients in the drug-interruption group developed antibodies against certolizumab pegol (and had lower plasma concentrations of certolizumab pegol) than the continuously treated group.
Certolizumab pegol effectively maintains remission of Crohn's disease for up to 18 months. Continuous therapy is more effective than interrupted therapy.
尚未报道抗肿瘤坏死因子培塞丽珠单抗的维持治疗安全性和疗效超过 6 个月。我们评估了克罗恩病患者皮下注射培塞丽珠单抗连续与间断维持治疗的长期疗效、安全性和免疫原性。
对 PEGylated Antibody Fragment Evaluation in Crohn's Disease：Safety and Efficacy（PRECiSE）2 试验第 6 周时应答诱导治疗的患者，随机分为培塞丽珠单抗（连续）或安慰剂（药物中断）组，治疗时间为第 6 周至第 26 周。完成 PRECiSE 2 试验的患者有资格进入正在进行的前瞻性开放标签延伸试验 PRECiSE 3，迄今为止，患者已接受培塞丽珠单抗（400mg）每 4 周治疗 54 周，目前不提供增加剂量的选择。疾病活动度采用 Harvey-Bradshaw 指数评估。
连续组和药物中断组第 26 周时 Harvey-Bradshaw 指数应答率分别为 56.3%和 37.6%，相应的缓解率分别为 47.9%和 32.4%。第 26 周时应答的患者中，连续组和药物中断组在 PRECiSE 2 开始后第 80 周的应答率分别为 66.1%和 63.3%；第 26 周时缓解的患者中，第 80 周缓解率分别为 62.1%和 63.2%。与连续治疗组相比，药物中断组有更多患者产生针对培塞丽珠单抗的抗体（且培塞丽珠单抗的血浆浓度更低）。
培塞丽珠单抗可有效维持克罗恩病缓解长达 18 个月。连续治疗比间断治疗更有效。
