Thalidomide Induced Remission in Early-Onset Crohn's Disease

Ricki Lewis, PhD

November 26, 2013

Thalidomide induced remission in children and adolescents with treatment-refractory Crohn's disease in 8 weeks, according to the results of a small randomized trial In addition, patients continued to respond beyond a year in an open-label continuation phase of the trial, researchers report in an article published in the November 27 issue of JAMA.

One quarter of patients with Crohn's disease developed it during childhood. Such early-onset cases tend to be more severe than adult-onset disease. Moreover, pediatric and adolescent patients may sustain permanent damage and are more likely to be resistant to or unable to tolerate standard treatment (ie, steroids or other immunosuppressive drugs).

About 30% of childhood-onset cases are refractory to standard treatment. Observational studies suggested the possible efficacy of thalidomide in treating Crohn's disease. Thalidomide is known for its teratogenicity but is an effective treatment for inflammatory diseases of the skin and mucous membranes, as well as for multiple myeloma.

In the current study, Marzia Lazzerini, PhD, from the Institute for Maternal and Child Health, Trieste, Italy, and colleagues evaluated thalidomide in children and adolescents with refractory Crohn's disease.

Between August 2008 and September 2012, the researchers enrolled 56 children from 6 pediatric care centers in Italy who did not respond to immunosuppressants. They randomly assigned them to receive either placebo (26) or thalidomide (28) daily for 8 weeks. Nonresponders to placebo received thalidomide for an additional 8 weeks. All responders continued to receive thalidomide for at least 52 weeks beyond the initial 8 weeks.

The primary outcome was remission according to reduction in the Pediatric Crohn Disease Activity Index score at 4 weeks (≥25%) and at 8 weeks (≥75%). During the open-label follow-up period, primary outcomes were 75% response and clinical remission.

More children in the treatment group went into remission compared with those in the placebo group (13/28 [46.4%] vs 3/26 [11.5%]). The thalidomide group showed evidence of improvement by 8 weeks, but not by 4 weeks.

Of the nonresponders to placebo who began receiving thalidomide, 11 (52.4%) of 21 reached remission by 8 weeks after treatment began. Overall, 31 (63.3%) of 49 of children who received the drug achieved clinical remission, and 32 (65.3%) of 49 achieved a 75% response.

Clinical remission persisted on average for 181 weeks (95% confidence interval, 144.53 - 217.76 weeks) vs 6.3 weeks (95% confidence interval, 3.51 - 9.15 weeks) in the placebo group (P < .001).

The investigators conclude that in children and adolescents with refractory Crohn's disease, thalidomide improved clinical remission better than placebo at the 8-week mark, as well as during a year of open-label follow-up.

A limitation of the study is the small number of participants. Replication of the findings is necessary to determine clinical utility of thalidomide as a first-line treatment for pediatric cases of Crohn's disease that have not responded to immunosuppressive drugs.

This study was supported by the Italian Medicines Agency. The drug producer (Pharmion until 2009; Celgene after 2009) provided the study drug. The authors have disclosed no relevant financial relationships.

JAMA. 2013;310:2164-2173.

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