Effect of thalidomide on clinical remission in children and adolescents with ulcerative colitis refractory to other immunosuppressives: Pilot randomized clinical trial

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 ManentiGiuliana Decorti, Sara De Iudicibus, Rossella Paparazzo, Marcella Montico, Alessandro Ventura

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1739-1749
Number of pages11
JournalInflammatory Bowel Diseases
Volume21
Issue number8
DOIs
Publication statusPublished - Apr 29 2015

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Thalidomide
Immunosuppressive Agents
Ulcerative Colitis
Randomized Controlled Trials
Placebos
Confidence Intervals
Numbers Needed To Treat
Odds Ratio
Amenorrhea
Peripheral Nervous System Diseases
Double-Blind Method
Crohn Disease
Therapeutics
Safety

Keywords

  • Children
  • Randomized clinical trial
  • Thalidomide
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Effect of thalidomide on clinical remission in children and adolescents with ulcerative colitis refractory to other immunosuppressives : Pilot randomized clinical trial. / Lazzerini, Marzia; Martelossi, Stefano; Magazzù, Giuseppe; Pellegrino, Salvatore; Lucanto, Maria Cristina; Barabino, Arrigo; Calvi, Angela; Arrigo, Serena; Lionetti, Paolo; Lorusso, Monica; Mangiantini, Francesca; Fontana, Massimo; Zuin, Giovanna; Palla, Gabriella; Maggiore, Giuseppe; Bramuzzo, Matteo; Pellegrin, Maria Chiara; Maschio, Massimo; Villanacci, Vincenzo; Manenti, Stefania; Decorti, Giuliana; De Iudicibus, Sara; Paparazzo, Rossella; Montico, Marcella; Ventura, Alessandro.

In: Inflammatory Bowel Diseases, Vol. 21, No. 8, 29.04.2015, p. 1739-1749.

Research output: Contribution to journalArticle

Lazzerini, M, Martelossi, S, Magazzù, G, Pellegrino, S, Lucanto, MC, Barabino, A, Calvi, A, Arrigo, S, Lionetti, P, Lorusso, M, Mangiantini, F, Fontana, M, Zuin, G, Palla, G, Maggiore, G, Bramuzzo, M, Pellegrin, MC, Maschio, M, Villanacci, V, Manenti, S, Decorti, G, De Iudicibus, S, Paparazzo, R, Montico, M & Ventura, A 2015, 'Effect of thalidomide on clinical remission in children and adolescents with ulcerative colitis refractory to other immunosuppressives: Pilot randomized clinical trial', Inflammatory Bowel Diseases, vol. 21, no. 8, pp. 1739-1749. https://doi.org/10.1097/MIB.0000000000000437
Lazzerini, Marzia ; Martelossi, Stefano ; Magazzù, Giuseppe ; Pellegrino, Salvatore ; Lucanto, Maria Cristina ; Barabino, Arrigo ; Calvi, Angela ; Arrigo, Serena ; Lionetti, Paolo ; Lorusso, Monica ; Mangiantini, Francesca ; Fontana, Massimo ; Zuin, Giovanna ; Palla, Gabriella ; Maggiore, Giuseppe ; Bramuzzo, Matteo ; Pellegrin, Maria Chiara ; Maschio, Massimo ; Villanacci, Vincenzo ; Manenti, Stefania ; Decorti, Giuliana ; De Iudicibus, Sara ; Paparazzo, Rossella ; Montico, Marcella ; Ventura, Alessandro. / Effect of thalidomide on clinical remission in children and adolescents with ulcerative colitis refractory to other immunosuppressives : Pilot randomized clinical trial. In: Inflammatory Bowel Diseases. 2015 ; Vol. 21, No. 8. pp. 1739-1749.
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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.",
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T1 - Effect of thalidomide on clinical remission in children and adolescents with ulcerative colitis refractory to other immunosuppressives

T2 - Pilot randomized clinical trial

AU - Lazzerini, Marzia

AU - Martelossi, Stefano

AU - Magazzù, Giuseppe

AU - Pellegrino, Salvatore

AU - Lucanto, Maria Cristina

AU - Barabino, Arrigo

AU - Calvi, Angela

AU - Arrigo, Serena

AU - Lionetti, Paolo

AU - Lorusso, Monica

AU - Mangiantini, Francesca

AU - Fontana, Massimo

AU - Zuin, Giovanna

AU - Palla, Gabriella

AU - Maggiore, Giuseppe

AU - Bramuzzo, Matteo

AU - Pellegrin, Maria Chiara

AU - Maschio, Massimo

AU - Villanacci, Vincenzo

AU - Manenti, Stefania

AU - Decorti, Giuliana

AU - De Iudicibus, Sara

AU - Paparazzo, Rossella

AU - Montico, Marcella

AU - Ventura, Alessandro

PY - 2015/4/29

Y1 - 2015/4/29

N2 - 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.

AB - 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.

KW - Children

KW - Randomized clinical trial

KW - Thalidomide

KW - Ulcerative colitis

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