Background Anti-tumor necrosis factor (TNF) therapy is effective for the treatment of Crohn's disease. Cessation may be considered in patients with a low risk of relapse. We aimed to externally validate and update our previously developed prediction model to estimate the risk of relapse after cessation of anti-TNF therapy. Methods We performed a retrospective cohort study in 17 Dutch hospitals. Crohn's disease patients in clinical, biochemical or endoscopic remission were included after anti-TNF cessation. Primary outcome was a relapse necessitating treatment. Discrimination and calibration of the previously developed model were assessed. After external validation, the model was updated. The performance of the updated prediction model was assessed in internal-external validation and by using decision curve analysis. Results 486 patients were included with a median follow-up of 1.7 years. Relapse rates were 35 and 54% after 1 and 2 years. At external validation, the discriminative ability of the prediction model was equal to that found at the development of the model [c-statistic 0.58 (95% confidence interval (CI) 0.54-0.62)], though the model was not well-calibrated on our cohort [calibration slope: 0.52 (0.28-0.76)]. After an update, a c-statistic of 0.60 (0.58-0.63) and calibration slope of 0.89 (0.69-1.09) were reported in internal-external validation. Conclusion Our previously developed and updated prediction model for the risk of relapse after cessation of anti-TNF in Crohn's disease shows reasonable performance. The use of the model may support clinical decision-making to optimize patient selection in whom anti-TNF can be withdrawn. Clinical validation is ongoing in a prospective randomized trial. Eur J Gastroenterol Hepatol 34: 983-992
Background
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.
Methods
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.
Results
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%.
Conclusions
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.
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