Department of Biomedicine, Unit of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Porto, Portugal.
Department of Gastroenterology, São João Hospital University Centre, Porto, Portugal.
United European Gastroenterol J. 2023 Jul;11(6):531-541. doi: 10.1002/ueg2.12420. Epub 2023 Jun 15.
Timely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD.
We aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression.
Data from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices.
The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p ≤ 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C-reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 μg/g) in at least one visit were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 μg/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%-63% probability of achieving the composite outcomes.
The combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making.
及时对克罗恩病（CD）进行分层对于患者的管理至关重要。使用非侵入性的准确生物标志物是监测治疗和追求黏膜愈合的关键，黏膜愈合是 CD 的最终治疗终点。
我们旨在评估现有生物标志物的性能，并开发风险矩阵以预测 CD 的进展。
收集了 289 名接受英夫利昔单抗（IFX）维持治疗 2 年的 CD 患者的数据；这些患者被纳入 DIRECT，一项前瞻性多中心观察性研究。使用包含临床和药物相关因素的两个综合结果来评估疾病进展，第一个结果包括 IFX 剂量和/或频率的调整。使用单变量和多变量逻辑回归计算优势比（OR）并开发风险矩阵。
在随访期间至少出现一次贫血是疾病进展的显著预测因子（复合结果 1 和 2 的 OR 分别为 2.436 和 3.396[ p≤0.001]），无论是否存在混杂因素。至少在一次就诊时孤立的高 C 反应蛋白（CRP；>10.0mg/L）和粪便钙卫蛋白（FC；>500.0μg/g）也是显著的预测因子，而较轻的升高（3.1-10.0mg/L 和 250.1-500.0μg/g）仅在至少两次就诊时（连续或不连续）检测到才有意义。在风险矩阵中组合生物标志物具有良好的预测进展的能力；同时在至少一次就诊时出现贫血、CRP 和 FC 显著升高的患者，达到复合结果的概率为 42%-63%。
在至少一个时间点同时评估血红蛋白、CRP 和 FC，并将其纳入风险矩阵，似乎是 CD 管理的最佳策略，因为来自额外就诊的信息并没有显著影响预测结果，反而可能会延迟决策。
