Longitudinal profiles of fecal calprotectin and C-reactive protein in relation to outcomes in Crohn’s disease patients on infliximab

Abstract Background and Aims This study explored the relationship between fecal calprotectin (FCAL) and C-reactive protein (CRP) trajectory classes and composite outcomes (COs) in Crohn’s disease (CD) patients under infliximab (IFX). COs reflected disease progression, including surgery, hospitalizations, new fistulas, abscesses, strictures, and treatment escalation. Methods The DIRECT study was a multicenter, prospective investigation (2016–2019), including moderate–severe CD patients on IFX. Latent class mixed models were used to identify subgroups based on longitudinal FCAL and CRP trajectories. Results FCAL trajectory analysis identified four clusters; CRP analysis revealed three. Patients in the U-shaped FCAL trajectory (Class 1) were more likely to achieve the global CO [odds ratio (OR) 3.263, 95% confidence interval (CI) 1.050–10.144, P = .041] and the CO without symptoms and IFX adjustments compared to those in the subthreshold decline (Class 4) (OR 9.639, 95% CI 1.147–81.025, P = .037). In CRP trajectories, patients in the upward trend (Class C) had a higher odds of achieving the global CO compared to the flat trajectory (Class B) (OR 2.171, 95% CI 1.059–4.449, P = .034). In multivariable regression models, class membership improved composite outcome discrimination. Conclusions Patients under IFX therapy with near or above-threshold FCAL levels or a history of high CRP were more likely to experience adverse outcomes. Regression analyses demonstrated that class membership provided additional prognostic value beyond baseline variables alone. These findings highlight the clinical relevance of trajectory-based monitoring for optimizing treatment strategies and underscore the importance of controlling inflammation early to prevent disease progression in CD.