Wong Rochelle, Charilaou Paris, Hemperly Amy, Qin Lihui, Pan Yushan, Mathani Prerna, Longman Randy, Boland Brigid S, Dulai Parambir S, Holmer Ariela K, Lukin Dana, Singh Siddharth, Valasek Mark A, Sandborn William J, Scherl Ellen, Vande Casteele Niels, Battat Robert
Division of Gastroenterology and Liver Diseases, Department of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Medicine, Section of Gastroenterology and Hepatology, Wake Forest Medical School, Charlotte, NC, USA.
Crohns Colitis 360. 2024 Nov 22;6(4):otae052. doi: 10.1093/crocol/otae052. eCollection 2024 Oct.
No models predict future outcomes in inflammatory bowel disease (IBD) patients receiving maintenance infliximab therapy. We created a predictive model for unfavorable outcomes.
Adult patients with IBD receiving maintenance infliximab therapy at 2 centers with matched serum infliximab concentrations and blinded histologic scores (Robarts Histopathologic Index [RHI]) were included. The primary endpoint was an unfavorable outcome of active objective inflammation or need for IBD-related surgery or hospitalization at 6-18 months follow-up. Internal variables were identified using univariable analyses, modeling used multivariable analysis, and performance was assessed (area under receiver-operating curve [AUC]) and externally validated.
In 81 patients, 40.7% developed unfavorable outcomes at follow-up. Infliximab concentration <9.3 µg/mL (odds ratio [OR] 5.3, = .001) and RHI > 12 (OR 3.4, = .03) were the only factors associated with developing the primary unfavorable outcome. A prediction score assigning 1 point to each variable had good discrimination and performed similarly on internal (AUC 0.71) and external (AUC 0.73) cohorts. The risk of primary unfavorable outcomes in internal and external cohorts, respectively, was 23% and 15% for a score of 0, 46% and 50% for a score of 1, and 100% and 75% for a score of 2. Infliximab concentration alone performed similar to the 2-predictor model in internal (AUC 0.65, = .5 vs. 2-predictor model) and external (AUC 0.70, = .9, vs. 2-predictor model) cohorts.
Using unbiased variable selection, a 2-predictor model using infliximab concentrations and histology identified IBD patients on maintenance infliximab therapy at high risk of future unfavorable outcomes. For practical applicability, infliximab concentrations alone performed similarly well.
目前尚无模型可预测接受英夫利昔单抗维持治疗的炎症性肠病（IBD）患者的未来结局。我们创建了一个预测不良结局的模型。
纳入在2个中心接受英夫利昔单抗维持治疗、血清英夫利昔单抗浓度匹配且组织学评分（罗伯茨组织病理学指数[RHI]）设盲的成年IBD患者。主要终点是在6至18个月随访时出现活动性客观炎症、需要进行IBD相关手术或住院等不良结局。通过单变量分析确定内部变量，使用多变量分析进行建模，并评估模型性能（受试者操作特征曲线下面积[AUC]）并进行外部验证。
81例患者中，40.7%在随访时出现不良结局。英夫利昔单抗浓度<9.3µg/mL（比值比[OR]5.3，P = 0.001）和RHI>12（OR 3.4，P = 0.03）是与出现主要不良结局相关的唯一因素。对每个变量赋予1分的预测评分具有良好的区分度，在内部（AUC 0.71）和外部（AUC 0.73）队列中的表现相似。内部和外部队列中，评分为0时主要不良结局的风险分别为23%和15%，评分为1时分别为46%和50%，评分为2时分别为100%和75%。仅英夫利昔单抗浓度在内部（AUC 0.65，P = 0.5，与双预测模型相比）和外部（AUC 0.70，P = 0.9，与双预测模型相比）队列中的表现与双预测模型相似。
通过无偏变量选择，使用英夫利昔单抗浓度和组织学的双预测模型可识别出接受英夫利昔单抗维持治疗且未来发生不良结局风险较高的IBD患者。就实际应用而言，仅英夫利昔单抗浓度的表现同样良好。
