Background and Aims The availability of biological agents for inflammatory bowel disease has increased over the past years. In this systematic review and meta‐analysis, we aimed to explore time trends in clinical response and clinical remission rates in Crohn's disease (CD) patients treated with biologics while discussing the need for new strategies. Methods MEDLINE, Cochrane, and ISI Web of Science databases were searched for randomized placebo‐controlled trials with biological agents in moderate‐to‐severe CD patients. Sub‐group and meta‐regression analyses compared treatment and placebo by calculating the pooled odds ratios of clinical remission and clinical response, across time categories and publication year. We also estimated the proportion of patients achieving clinical remission and clinical response by comparing both groups according to the publication year. Results Twenty‐five trials were included in the systematic review, which enrolled 8879 patients between 1997 and 2022. The clinical remission and clinical response odds, in induction and maintenance, have been constant over time, as no statistically significant differences were found between time categories (interaction p‐values: clinical remission [induction, p = 0.19; maintenance, p = 0.24]; clinical response [induction, p = 0.43; maintenance, p = 0.59]). In meta‐regression analyses, publication year did not influence these outcomes (clinical remission [induction, OR 1.01{95% CI 0.97–1.05}, p = 0.72; clinical response [induction, OR 1.01{95% CI 0.97–1.04]; p = 0.63; maintenance, OR 1.03{95% CI 0.98–1.07}; p = 0.21]), with the exception of clinical remission in maintenance studies, which presented a decreased effect (odds ratio 0.97{95% CI 0.94–1.00}, p = 0.03]). Conclusions Our review highlights that the odds of clinical outcomes in CD patients receiving biological treatment relative to placebo have been stable in the last decades.

Background: 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. Objective:We aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression.Methods: 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. Results: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. Conclusion: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.