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

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.

• Authors: Marzia Lazzerini, Stefano Martelossi, Giuseppe Magazzù, Salvatore Pellegrino, Maria Cristina Lucanto, Arrigo Barabino, Angela Calvi, Serena Arrigo, Paolo Lionetti, Monica Lorusso, Francesca Mangiantini, Massimo Fontana, Giovanna Zuin, Gabriella Palla, Giuseppe Maggiore, Matteo Bramuzzo, Maria Chiara Pellegrin, Massimo Maschio, Vincenzo Villanacci, Stefania Manenti, Giuliana Decorti, Sara De Iudicibus, Rossella Paparazzo, Marcella Montico, Alessandro Ventura
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 21 Issue 8 Pg. 1739-49 (Aug 2015) ISSN: 1536-4844 [Electronic] England
• PMID: 26185909 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Thalidomide

Topics

• 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)