Effect of Thalidomide on Clinical Remission in Children and Adolescents with Ulcerative Colitis Refractory to Other Immunosuppressives: Pilot Randomized Clinical Trial

Inflamm Bowel Dis. 2015 Aug;21(8):1739-49. doi: 10.1097/MIB.0000000000000437.

Abstract

Background: In a randomized controlled trial, thalidomide has shown to be effective in refractory Crohn's disease in children. This pilot study aimed at evaluating thalidomide in refractory pediatric ulcerative colitis (UC).

Methods: Double-blind, placebo-controlled randomized clinical trial on thalidomide 1.5 to 2.5 mg/kg/day in children with active UC despite multiple immunosuppressive treatments. In an open-label extension, nonresponders to placebo received thalidomide for an additional 8 weeks; all responders were followed up for a minimum of 52 weeks.

Results: Twenty-six children with refractory UC were randomized to thalidomide or placebo. Clinical remission at week 8 was achieved by significantly more children treated with thalidomide {10/12 (83.3%) versus 2/11 (18.8%); risk ratio, 4.5 (95% confidence interval [CI], 1.2-16.4); P = 0.005; number needed to treat, 1.5}. Of the nonresponders to placebo who were switched to thalidomide, 8 of 11 (72.7%) subsequently reached remission at week 8 (risk ratio, 4.0 [95% CI, 1.1-14.7]; number needed to treat, 2.45; P = 0.01). Clinical remission in the thalidomide group was 135.0 weeks (95% CI, 32-238), compared with 8.0 weeks (95% CI, 2.4-13.6) in the placebo group (P < 0.0001). Cumulative incidence of severe adverse events was 3.1 per 1000 patient-weeks. Peripheral neuropathy and amenorrhea were the most frequent adverse events.

Conclusions: In this pilot randomized controlled trial on cases of UC refractory to immunosuppressive therapy, thalidomide compared with placebo resulted in improved clinical remission at 8 weeks of treatment and in longer term maintenance of remission. These findings require replication in larger clinical studies evaluating both thalidomide efficacy and safety.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Colitis, Ulcerative / drug therapy*
  • Double-Blind Method
  • Drug Resistance / drug effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Pilot Projects
  • Prognosis
  • Remission Induction
  • Salvage Therapy*
  • Thalidomide / therapeutic use*

Substances

  • Immunosuppressive Agents
  • Thalidomide

Supplementary concepts

  • Pediatric ulcerative colitis