Gastroenterology Department, Sheba Medical Center, Tel Hashomer, Tel-Aviv University, Israel.
Inflamm Bowel Dis. 2012 Nov;18(11):2026-33. doi: 10.1002/ibd.22902. Epub 2012 Jan 31.
Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose-doubling.
A multicenter retrospective study of CD patients losing response to infliximab was undertaken. The clinical outcome of patients whose infusion intervals were halved (5 mg/kg/4 weeks) was compared with patients treated by dose-doubling (10 mg/kg/8 weeks).
In all, 168 patients were included from 18 centers in Europe, USA, and Israel. Of these, 112 were intensified by dose-doubling and 56 received interval-halving strategy. Early response to dose-escalation was experienced by 86/112 (77%) patients in the dose-doubling group compared with 37/56 patients (66%) in the interval-halving group (odds ratio [OR] 1.7, 95% confidence interval [CI] 0.8-3.4, P = 0.14). Sustained clinical response at 12 months postescalation was maintained in 50% of patients in the dose-doubling group compared with 39% in the interval-halving group (OR 1.5, 95% CI 0.8-2.9, P = 0.2). On multivariate analysis, predictors of long-term response to escalation were a nonsmoking status, CD diagnosis between 16-40 years of age, and normal C-reactive protein (CRP).
Dose intensification leads to a sustained regained response in 47% of CD patients who lost response to standard infliximab dose, but halving the infusion intervals is probably not superior to dose-doubling. Given the costs and patient inconvenience incurred by an additional infusion visit, the dose-doubling strategy may be preferable to the interval-halving strategy.
在克罗恩病（CD）患者对药物失去反应时，通常会加强英夫利昔单抗治疗，但尚无数据表明减半间隔是否优于加倍剂量。我们旨在评估与剂量加倍相比，通过间隔减半来增强英夫利昔单抗剂量的疗效。
对失去英夫利昔单抗反应的 CD 患者进行了一项多中心回顾性研究。将输注间隔减半（5mg/kg/4 周）的患者的临床结果与接受剂量加倍（10mg/kg/8 周）的患者进行比较。
共纳入来自欧洲、美国和以色列的 18 个中心的 168 例患者。其中，112 例患者通过剂量加倍进行强化治疗，56 例患者采用间隔减半策略。在剂量加倍组中，86/112（77%）的患者早期对剂量升级有反应，而间隔减半组中，37/56（66%）的患者有反应（比值比 [OR] 1.7，95%置信区间 [CI] 0.8-3.4，P=0.14）。在剂量升级后 12 个月，剂量加倍组中 50%的患者维持持续的临床缓解，而间隔减半组中为 39%（OR 1.5，95%CI 0.8-2.9，P=0.2）。多变量分析显示，长期对升级有反应的预测因素是非吸烟状态、16-40 岁之间的 CD 诊断以及正常 C 反应蛋白（CRP）。
在失去标准英夫利昔单抗剂量反应的 CD 患者中，有 47%的患者通过剂量强化治疗可获得持续的缓解，但减半间隔可能并不优于剂量加倍。鉴于增加一次输注就诊带来的成本和患者不便，剂量加倍策略可能优于间隔减半策略。
