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 language | English |
|---|---|
| Pages (from-to) | 1739-1749 |
| Number of pages | 11 |
| Journal | Inflammatory Bowel Diseases |
| Volume | 21 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Apr 29 2015 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84925324411&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925324411&partnerID=8YFLogxK
U2 - 10.1097/MIB.0000000000000437
DO - 10.1097/MIB.0000000000000437
M3 - Article
C2 - 26185909
AN - SCOPUS:84925324411
VL - 21
SP - 1739
EP - 1749
JO - Inflammatory Bowel Diseases
JF - Inflammatory Bowel Diseases
SN - 1078-0998
IS - 8
ER -