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Randomized Trial Comparing 5-Year Follow-Up of First-Line Infliximab to Conventional Therapy in Pediatric Crohn's
S A Vuijk1, M M E Jongsma1, M A Cozijnsen1
1Department of Paediatric Gastroenterology, Erasmus Medical Centre-Sophia Children's Hospital, Rotterdam, The Netherlands.
Insights
First-line infliximab (FL-IFX) in children with Crohn's disease (CD) delayed the need for additional biologic therapy by 5 years. However, most patients required further treatment regardless of initial therapy for moderate-to-severe CD.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Clinical Therapeutics
Background:
- The TISKids study previously showed first-line infliximab (FL-IFX) superior to conventional therapy for pediatric Crohn's disease (CD) at 52 weeks.
- This study investigates the long-term 5-year outcomes of this cohort.
Purpose of the Study:
- To evaluate sustained clinical remission and treatment escalation at 5 years in children with moderate-to-severe CD treated with FL-IFX versus conventional therapy.
- To compare the time to initiation or re-initiation of biologic therapy between the two groups.
Main Methods:
- A multicenter, open-label randomized controlled trial involving newly diagnosed, untreated pediatric CD patients (aged 3-17 years).
- Patients were randomized to FL-IFX (5 infusions, then stopped) or conventional treatment, both with azathioprine maintenance.
- Primary outcome: sustained clinical remission without additional CD-related therapy at 5 years. Secondary outcome: time to (re)start biologic therapy.
Main Results:
- At 5 years, sustained remission without additional therapy was low in both groups (6% FL-IFX vs. 2% conventional; p=0.617).
- The majority of patients required additional CD-related treatment (88% FL-IFX vs. 86% conventional; p=0.271).
- FL-IFX significantly delayed the median time to (re)start biologic therapy (65 weeks vs. 31 weeks; p=0.037).
Conclusions:
- Nearly all pediatric patients with moderate-to-severe CD require additional CD-related treatment by 5 years, irrespective of initial therapy.
- FL-IFX induction therapy demonstrated a benefit by delaying the need for subsequent biologic treatments.
- Early and sustained treatment, potentially including infliximab, is crucial for managing moderate-to-severe 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.
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