Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
Clin Gastroenterol Hepatol. 2014 Sep;12(9):1474-81.e2; quiz e91. doi: 10.1016/j.cgh.2014.01.033. Epub 2014 Jan 29.
BACKGROUND & AIMS: Few agents are available for the treatment of inflammatory bowel diseases, and patients frequently become unresponsive to biologics. We investigated the feasibility of reinitiating infliximab therapy for patients who previously received only episodic therapy with, lost response to, or had infusion reactions to infliximab. We also aimed to identify factors associated with the success and safety of restarting infliximab, such as antibodies to infliximab and trough levels of the drug.
From the inflammatory bowel disease biobank, we identified 128 consecutive patients (105 patients with Crohn's disease, 23 patients with ulcerative colitis) who restarted infliximab after a median 15-month discontinuation (range, 6-125 mo; 28 patients for loss of response or infusion reactions, 100 patients for remission or pregnancy). We also analyzed serum samples that had been collected during the first period of infliximab therapy (T-1), when therapy was reinitiated (T0), and at later time points (T+1, T+2) for trough levels and antibodies to infliximab. We investigated correlations among response to treatment, infusion reactions, treatment modalities, trough levels, and antibodies to infliximab.
Reinitiation of infliximab therapy produced a response in 84.5% of patients at week 14, 70% of patients at 1 year, and in 61% of patients at more than 4 years. Fifteen patients had acute infusion reactions and 10 patients had delayed infusion reactions. The absence of antibodies to infliximab at T+1 (hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.026-0.74; P = .021) and reinitiation with concomitant immunomodulator therapy were associated with short-term responses (HR, 6.0; 95% CI, 1.3-27; P = .019). Pregnancy or remission as reason for discontinuation (HR, 2.70; 95% CI, 1.09-6.67; P = .033) and higher trough levels at T+1 (HR, 2.94; 95% CI, 1.18-7.69; P = .021) were associated with long-term response. Undetectable antibodies to infliximab at T+1 were associated with the safety of reinitiating therapy (HR for infusion reaction with detectable antibodies to infliximab, 7.7; 95% CI, 1.88-31.3; P = .004).
Reinitiating infliximab therapy can be safe and effective for patients with Crohn's disease or ulcerative colitis after a median 15-month discontinuation period.
目前用于治疗炎症性肠病的药物寥寥无几，而且患者常常对生物制剂失去反应。我们研究了重新启动英夫利昔单抗治疗的可行性，这些患者之前仅接受过间歇性治疗，对英夫利昔单抗失去了反应，或出现了输注反应。我们还旨在确定与重新启动英夫利昔单抗的安全性和疗效相关的因素，例如针对英夫利昔单抗的抗体和药物谷浓度。
从炎症性肠病生物库中，我们确定了 128 例连续患者（105 例克罗恩病患者，23 例溃疡性结肠炎患者），他们在中位停药 15 个月后重新开始使用英夫利昔单抗（范围为 6-125 个月；28 例因失去反应或输注反应，100 例因缓解或妊娠而停药）。我们还分析了在英夫利昔单抗治疗的第一个时期（T-1）、重新开始治疗时（T0）和以后的时间点（T+1、T+2）收集的血清样本，以检测药物谷浓度和针对英夫利昔单抗的抗体。我们研究了治疗反应、输注反应、治疗方式、药物谷浓度和针对英夫利昔单抗的抗体之间的相关性。
重新启动英夫利昔单抗治疗后，14 周时 84.5%的患者有反应，1 年时 70%的患者有反应，4 年以上时 61%的患者有反应。15 例患者出现急性输注反应，10 例患者出现迟发性输注反应。在 T+1 时未检测到针对英夫利昔单抗的抗体（风险比 [HR]，0.14；95%置信区间 [CI]，0.026-0.74；P =.021）和同时使用免疫调节剂进行重新启动与短期反应相关（HR，6.0；95%CI，1.3-27；P =.019）。停药的原因是妊娠或缓解（HR，2.70；95%CI，1.09-6.67；P =.033）和 T+1 时较高的药物谷浓度（HR，2.94；95%CI，1.18-7.69；P =.021）与长期反应相关。在 T+1 时未检测到针对英夫利昔单抗的抗体与重新开始治疗的安全性相关（T+1 时检测到针对英夫利昔单抗的抗体的输注反应风险比，7.7；95%CI，1.88-31.3；P =.004）。
在中位停药 15 个月后，重新启动英夫利昔单抗治疗对克罗恩病或溃疡性结肠炎患者既安全又有效。
