Influence of Trough Serum Levels and Immunogenicity on Long-term Outcome of Adalimumab Therapy in Crohn's Disease
Influence of Trough Serum Levels and Immunogenicity on Long-term Outcome of Adalimumab Therapy in Crohn's Disease
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DOI：
10.1053/j.gastro.2009.07.062
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发表时间：
2009-11-01
期刊：
影响因子：
29.4
通讯作者：
Rutgeerts, Paul
中科院分区：
文献类型：
--
作者：
Karmiris, Konstantinos;Paintaud, Gilles;Rutgeerts, Paul
背景与目的：阿达利单抗是治疗活动期克罗恩病的有效方法，但长期资料缺乏。我们进行了一项观察性研究，以评估对英夫利昔单抗无效的患者使用阿达利单抗的长期临床益处，特别是关注低谷血清浓度和抗阿达利单抗抗体对临床结果的影响。方法：共有168名克罗恩病患者在三级中心接受阿达利单抗治疗，纳入一项前瞻性随访计划。用酶联免疫吸附试验检测预定时间点的血药浓度和抗阿达单抗抗体。结果：分别有71%和67%的患者在第4周和第12周有反应；其中61.5%的患者表现出持续的临床益处，直到随访结束(中位数[四分位数范围]，20.4[11.7-30.0]个月)。在接受维持治疗的156名患者中，102名(65.4%)不得不每周增加到40毫克，60名(38.5%)最终停止阿达利单抗治疗，主要原因是失去反应。与继续接受阿达单抗治疗的患者相比，在整个随访期内，停止治疗的患者的血药浓度显著低于继续接受阿达利马治疗的患者。9.2%的患者存在抗阿达利单抗抗体，并影响血清浓度。12%的患者发生严重不良事件。结论：在英夫利昔单抗治疗失败后，在中位数近2年的随访期内，2/3的患者获得了持续的临床益处。停药与阿达单抗血药浓度低直接相关，在产生抗阿达单抗抗体的患者中观察到更多。
BACKGROUND & AIMS: Adalimumab is an efficacious therapy for active Crohn's disease, but long-term data are scarce. We conducted an observational study to assess the long-term clinical benefit of adalimumab in patients who failed to respond to infliximab, specifically focusing on the influence of trough serum concentration and antibodies against adalimumab on clinical outcome. METHODS: A total of 168 patients with Crohn's disease treated with adalimumab in a tertiary center were included in a prospective follow-up program. Trough serum concentration and antibodies against adalimumab were measured at predefined time points using enzyme-linked immunosorbent assays. RESULTS: A total of 71% and 67% of patients responded by weeks 4 and 12, respectively; among them, 61.5% demonstrated sustained clinical benefit until the end of follow-up (median [interquartile range], 20.4 [11.7-30.0] months). Of the 156 patients receiving maintenance therapy, 102 (65.4%) had to step up to 40 mg weekly and 60 (38.5%) eventually stopped adalimumab therapy mainly due to loss of response. Significantly lower adalimumab trough serum concentrations were measured throughout the follow-up period in patients who discontinued therapy as compared with patients who stayed on adalimumab. Antibodies against adalimumab were present in 9.2% of the patients and affected trough serum concentration. Serious adverse events occurred in 12% of the patients. CONCLUSIONS: Introduction of adalimumab after failure of infliximab therapy resulted in a sustained clinical benefit in two thirds of patients during a median follow-up period of almost 2 years. Discontinuation was directly related to low adalimumab trough serum concentration, which was observed more frequently in patients who developed antibodies against adalimumab.