Induction and maintenance therapy with infliximab for children with moderate to severe ulcerative colitis
Jeffrey Hyams1, Lakshmi Damaraju, Marion Blank
1Division of Digestive Diseases and Nutrition, Connecticut Children’s Medical Center, 282 Washington Street, Hartford, Connecticut 06106, USA. jhyams@ccmckids.org
Insights
Infliximab effectively treated pediatric ulcerative colitis (UC), inducing a response in 73.3% of patients. By week 54, 28.6% achieved remission, with a favorable safety profile in this study of pediatric UC patients.
Area of Science:
- Pediatric Gastroenterology
- Immunopharmacology
- Inflammatory Bowel Disease Research
Background:
- Ulcerative colitis (UC) significantly impacts children's quality of life.
- Conventional therapies often fail or are poorly tolerated in pediatric UC.
- There is a need for effective treatments for moderate to severe pediatric UC.
Purpose of the Study:
- To assess infliximab's efficacy in inducing and maintaining clinical response in pediatric UC.
- To evaluate the safety and tolerability of infliximab in this population.
- To compare maintenance dosing strategies (every 8 vs. 12 weeks) for infliximab therapy.
Main Methods:
- A cohort of pediatric patients (6-17 years) with active UC received infliximab (5 mg/kg) at weeks 0, 2, and 6.
- Response at week 8 was defined by significant improvements in Mayo scores and rectal bleeding.
- Responders were randomized to infliximab every 8 (q8w) or 12 weeks (q12w) through week 54, with remission defined by the Pediatric UC Activity Index.
Main Results:
- Infliximab induced a clinical response in 73.3% of pediatric UC patients by week 8.
- Among responders, remission rates at week 54 were higher with q8w (38.1%) versus q12w (18.2%) infliximab.
- The overall estimated remission rate at week 54 was 28.6%, with no significant differences in serious adverse events or infusion reactions between dosing groups.
Conclusions:
- Infliximab is a safe and effective induction therapy for moderate to severe pediatric UC unresponsive to conventional treatments.
- Maintenance therapy with infliximab every 8 weeks may offer a higher remission rate compared to every 12 weeks.
- Infliximab demonstrated a favorable safety profile, with no reported deaths, malignancies, or opportunistic infections.
Background & Aims:
We evaluated the efficacy and safety of infliximab for inducing and maintaining benefit in children with moderately to severely active ulcerative colitis (UC).
Methods:
Patients (6-17 years old) who had active UC (Mayo scores of 6-12; endoscopic subscores ≥ 2) and had not responded to or tolerated conventional treatment were given 5 mg/kg infliximab at weeks 0, 2, and 6. The primary end point was response at week 8 (decreases in Mayo scores ≥ 30% and ≥ 3 points and decreases in rectal bleeding subscores of ≥ 1 or an absolute subscore of ≤ 1). At week 8, only responders were randomly assigned to groups given infliximab every 8 or 12 weeks (q8w or q12w) and followed through week 54. Maintenance end points included pediatric UC activity index scores <10 points, defined as remission.
Results:
At week 8, infliximab induced a response in 73.3% of patients (44 of 60) (95% confidence interval, 62.1%-84.5%; a positive result was defined by 95% confidence interval lower limit >40%). Among responders, twice as many were in remission at week 54 after q8w (8 of 21, 38.1%) than q12w (4 of 22, 18.2%; P = .146) therapy. Assuming the q8w remission rate for responders, the overall remission rate at week 54 would be 28.6%. Serious adverse events and infusion reactions occurred in similar proportions in the q8w and q12w groups. No deaths, malignancies, opportunistic infections, tuberculosis, or delayed hypersensitivity reactions were reported.
Conclusions:
Infliximab was safe and effective, inducing a response at week 8 in 73.3% of pediatric patients with moderate to severely active UC who did not respond to conventional therapy. The overall remission rate at week 54 for all enrolled patients was 28.6%, assuming the more effective q8w remission rate.
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