Subtherapeutic infliximab trough levels and complete mucosal healing are associated with sustained clinical remission after infliximab cessation in paediatric-onset Crohn's disease patients treated with combined immunosuppressive therapy

Background and Aims: We aimed to investigate the outcome in paediatric-onset Crohn's disease patients who had discontinued infliximab after maintaining clinical remission with combined immunosuppression, and to determine factors associated with clinical relapse. Methods: We conducted a retrospective observational study of 63 paediatric-onset Crohn's disease patients who had stopped scheduled infliximab during sustained corticosteroid-free clinical remission for at least 1 year with infliximab and azathioprine, and were followed up for at least 1 year thereafter. Cumulative relapse rates and the median time to relapse were estimated statistically. Factors at cessation were also evaluated for their association with clinical relapse. Results: After a median follow-up period of 4.3 years [range, 1-7.5 years], 60.3% [38/63] of patients had experienced clinical relapse. According to Kaplan-Meier survival analysis, the estimated cumulative relapse rates at 1, 4, and 6 years were 19.0%, 62.2%, and 75.2%, respectively, and the median relapse time was 3.3 years from infliximab cessation. According to multivariate Cox proportional hazard regression analysis, infliximab trough levels of ≥2.5 μg/mL and incomplete mucosal healing were associated with clinical relapse (hazard ratio [HR] = 7.199, 95% confidence interval [CI] = 1.641-31.571, p = 0.009 and HR = 3.628, 95% CI = 1.608-8.185, p = 0.002, respectively). Although re-treatment with infliximab was effective in 90.9% [30/33] of patients, 7.9% [3/38] eventually underwent surgery within 1 year of relapse. Conclusions: Considering the high cumulative relapse rates in the long term and cases of severe relapse requiring surgery, discontinuing infliximab in paediatric-onset Crohn's disease patients is currently inadvisable. However, there may be a subgroup of patients who are good candidates for infliximab withdrawal.