Abstract

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.

Original languageEnglish
Pages (from-to)1671-1686.e16
JournalClinical Gastroenterology and Hepatology
Volume20
Issue number8
DOIs
StatePublished - Aug 2022

Funding

FundersFunder number
Amgen Biogen
Department of Gastroenterology and Hepatology
Department of Gastroenterology, Sheba Medical Center
Division of Gastroenterology
Erasmus Erasmus University Medical Centre
Faes Farma
Falk Benelux
Hospital Universitario Virgen del Rocío
Klaudia Farkas
Leeds Teaching Hospitals
Liver Unit
Mitsubishi Pharma
National Health Service Foundation Trust
National Health Service Trust
Royal Hallamshire Hospital
Sackler School of Medicine
Samsung Bioepis
Sheffield Teaching Hospitals National Health Service Foundation Trust
Shomron Ben-Horin
St James's University Hospital
Tillotts
Vifor
Zeidler Ledcor Center
Pfizer
Merck
Roche
Gilead Sciences
Teva Pharmaceutical Industries
AbbVie
Meso Scale Diagnostics
Takeda Pharmaceutical Company
Janssen Pharmaceuticals
Hospira
University of Alberta
Herlev Hospital
Shire
Tel Aviv University
Ferring Pharmaceuticals
Vifor Pharma
Erasmus Universitair Medisch Centrum Rotterdam
Tillotts Pharma
Sheffield Teaching Hospitals NHS Foundation Trust
Dr. Falk Pharma

    Keywords

    • Anti-TNF Cessation
    • Crohn's Disease
    • Prediction

    Fingerprint

    Dive into the research topics of 'Prediction of Relapse After Anti–Tumor Necrosis Factor Cessation in Crohn's Disease: Individual Participant Data Meta-analysis of 1317 Patients From 14 Studies'. Together they form a unique fingerprint.

    Cite this