Fecal calprotectin is an early predictor of endoscopic response and histologic remission after the start of vedolizumab in inflammatory bowel disease

Background and aims: Early prediction of the effect of vedolizumab (VDZ) in inflammatory bowel disease (IBD) is of paramount importance to guide clinical decisions. This study assessed whether early fecal calprotectin (FC) can predict endoscopic response and histologic remission after VDZ initiation. Methods: This was a prospective study. Inclusion criteria were endoscopic inflammation and FC >100 µg/g. FC was determined at baseline and weeks 2, 4, 8 and 16. At week 16, endoscopies with ileal and colonic biopsies were performed. FC changes were assessed with Wilcoxon Rank Sum tests. ROC statistics were used to assess the diagnostic accuracy of FC. Results: In total, 45 patients [27 Crohn’s disease (CD), 16/2 ulcerative colitis (UC)/IBD-unclassified] [40% males, median age 39 (28–51) years] were included. Week 16 endoscopic response and histologic remission rates were 58% and 33%. A median 37% decline in FC at week 2 was observed only in endoscopic responders, p = 0.025. FC <250 µg/g at week 8 predicted endoscopic response in both UC and CD (positive predictive value 100%), whereas absence of FC decline at week 8 corresponded with absence of endoscopic response in CD [negative predictive value (NPV) 82%] and absence of histologic remission in both UC and CD (NPV 90%). Conclusion: The onset of a decline in FC as early as week 2 is associated with endoscopic response to VDZ induction. FC <250 µg/g at week 8 is associated with endoscopic response, whereas absence of FC decline at week 8 is associated with absence of both endoscopic response and histologic remission. FC levels 8 weeks after the start of VDZ could be used to guide clinical decisions and might substitute for endoscopic response evaluation

Prediction of Relapse After Anti–Tumor Necrosis Factor Cessation in Crohn's Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies

Background & Aims: Tools for stratification of relapse risk of Crohn's disease (CD) after anti–tumor necrosis factor (TNF) therapy cessation are needed. We aimed to validate a previously developed prediction model from the diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressants (STORI) trial, and to develop an updated model. Methods: Cohort studies were selected that reported on anti-TNF cessation in 30 or more CD patients in remission. Individual participant data were requested for luminal CD patients and anti-TNF treatment duration of 6 months or longer. The discriminative ability (concordance-statistic [C-statistic]) and calibration (agreement between observed and predicted risks) were explored for the STORI model. Next, an updated prognostic model was constructed, with performance assessment by cross-validation. Results: This individual participant data meta-analysis included 1317 patients from 14 studies in 11 countries. Relapses after anti-TNF cessation occurred in 632 of 1317 patients after a median of 13 months. The pooled 1-year relapse rate was 38%. The STORI prediction model showed poor discriminative ability (C-statistic, 0.51). The updated model reached a moderate discriminative ability (C-statistic, 0.59), and included clinical symptoms at cessation (hazard ratio [HR], 2.2; 95% CI, 1.2–4), younger age at diagnosis (HR, 1.5 for A1 (age at diagnosis ≤16 years) vs A2 (age at diagnosis 17 - 40 years); 95% CI, 1.11–1.89), no concomitant immunosuppressants (HR, 1.4; 95% CI, 1.18–172), smoking (HR, 1.4; 95% CI, 1.15–1.67), second line anti-TNF (HR, 1.3; 95% CI, 1.01–1.69), upper gastrointestinal tract involvement (HR, 1.3 for L4 vs non-L4; 95% CI, 0.96–1.79), adalimumab (HR, 1.22 vs infliximab; 95% CI, 0.99–1.50), age at cessation (HR, 1.2 per 10 years younger; 95% CI, 1–1.33), C-reactive protein (HR, 1.04 per doubling; 95% CI, 1.00–1.08), and longer disease duration (HR, 1.07 per 5 years; 95% CI, 0.98–1.17). In subanalysis, the discriminative ability of the model improved by adding fecal calprotectin (C-statistic, 0.63). Conclusions: This updated prediction model showed a reasonable discriminative ability, exceeding the performance of a previously published model. It might be useful to guide clinical decisions on anti-TNF therapy cessation in CD patients after further validation. © 2021 AGA Institut

Discontinuation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn's Disease

The risk of relapse after anti-tumour necrosis factor [TNF] therapy discontinuation in Crohn's disease patients with perianal fistulas [pCD] is unclear. We aimed to assess this risk.A systematic literature search was conducted to identify cohort studies on the incidence of relapse following anti-TNF discontinuation in pCD patients. Individual Participant Data were requested from the original study cohorts. Inclusion criteria were age ≥16 years, pCD as (co)indication for start of anti-TNF therapy, >3 doses, and remission of luminal and pCD at anti-TNF discontinuation. Primary outcome was the cumulative incidence of CD relapse using Kaplan-Meier estimates. Secondary outcomes included response to retreatment and risk factors associated with relapse as assessed by Cox regression analysis.309 patients from 12 studies in 10 countries were included. Median duration of anti-TNF treatment was 14 months [IQR 5.8 - 32.5]. Most patients were treated for pCD without active luminal disease [89%], received first line anti-TNF therapy [87%] and continued immunomodulatory following anti-TNF discontinuation [78%]. Overall cumulative incidence of relapse was 36% [95% CI 25-48%] and 42% [95% CI 32-53%] at 1 and 2 years after anti-TNF discontinuation. Risk factors for relapse included smoking [HR 1.5 (1.0, 2.1)] and history of proctitis [HR 1.7 (1.1, 2.5)]. Overall retreatment response rate was 82%.This IPD-MA, on predominantly patients with pCD without active luminal disease and first line anti-TNF therapy, shows that over half of patients remain in remission 2 years after anti-TNF discontinuation. Therefore, anti-TNF discontinuation may be considered in this subgroup