Randomized Trial Comparing 5-Year Follow-Up of First-Line Infliximab to Conventional Therapy in Pediatric Crohn's Disease.

BACKGROUND & AIMS: The TISKids study previously demonstrated that first-line infliximab was more effective than conventional treatment in achieving clinical remission without treatment escalation at 52 weeks in children with moderate-to-severe Crohn's disease. We investigated 5-year outcomes.

METHODS

The TISKids study is a multicenter, open-label, randomized controlled trial in newly diagnosed, untreated patients with Crohn's disease aged 3 to 17 years (weighted Pediatric Crohn's Disease Activity Index >40). Patients were randomized to first-line infliximab (5 infliximab infusions, then stopped) or conventional treatment (exclusive enteral nutrition or prednisolone). Both groups received azathioprine maintenance. The primary outcome was sustained clinical remission (weighted Pediatric Crohn's Disease Activity Index <12.5, Crohn's Disease Activity Index <150, or Physician Global Assessment remission) without additional Crohn's disease-related therapy at 5 years. Secondary outcomes included time to (re)start infliximab or another biological treatment.

RESULTS

One hundred patients were randomized; 6 were lost to follow-up. At 5 years, sustained clinical remission without additional Crohn's disease-related therapy was observed in 3 of 48 (6%) first-line infliximab patients vs 1 of 46 (2%) conventionally treated patients (P = .617), whereas 42 of 48 (88%) in first-line infliximab and 44 of 46 conventionally treated patients required additional Crohn's disease-related treatment (P = .271). The median time to the (re)start of biologic therapy was 65 weeks (95% confidence interval, 53-122 weeks) for first-line infliximab vs 31 weeks (95% confidence interval, 22-57 weeks) for conventional treatment (P = .037).

CONCLUSIONS

After 5 years of follow-up in the TISKids trial, we found that almost all patients required additional Crohn's disease-related treatment, irrespective of induction therapy with 5 infusions of first-line infliximab or conventional treatment. First-line infliximab delayed the need for additional biological treatment, indicating its potential as preferred treatment option for patients with moderate-to-severe Crohn's disease at diagnosis. These findings underscore that patients with moderate-to-severe Crohn's disease require early and maintained treatment with infliximab. This trial is registered in the European Clinical Trials Register (EudraCT 2014-005702-37) and on https://clinicaltrials.gov/study/NCT02517684, Number: NCT02517684.