Efficacy of long-term treatment with thalidomide in children and young adults with Crohn disease: preliminary results.
BACKGROUND
Several proinflammatory cytokines are involved in the pathogenesis of inflammatory bowel diseases. A significant role has been given to tumor necrosis factor alpha (TNF-alpha) as a guide proinflammatory cytokine. Thalidomide selectively reduces TNF-alpha production by inflammatory cells. The aim of the study was to assess the efficacy of thalidomide to induce and maintain remission in refractory Crohn disease.


METHODS
The decision to administer thalidomide was made on the basis of patient intolerance or resistance to conventional medical treatment or as the last medical resort before surgical intervention. Only 5 of 96 patients with inflammatory bowel disease satisfied these criteria. All five patients had Crohn disease (male: mean age, 17 years). Thalidomide was administered at night at a dose of 1.5-2 mg/kg/day. The Pediatric Crohn Disease Activity Index, modified Harvey-Bradshaw scores, and steroids reduction were used to assess clinical response.


RESULTS
Disease activity decreased consistently in four patients with a reduction of mean Pediatric Crohn Disease Activity Index from 36,9 to 2,5 and the mean Harvey-Bradshaw from 8.5 to 0.75 after 3 months of treatment. Steroid treatment (mean dose, 35 mg/day before treatment) was tapered and then discontinued, in four patients, within 1-3 months. Four patients are in remission after 19-24 months of treatment. The fifth patient discontinued thalidomide after 1 week because of distal paresthesia.


CONCLUSIONS
Thalidomide seems to be an effective and safe treatment in patients with refractory Crohn disease. This is the first report of long-term use of thalidomide in refractory Crohn disease in pediatric patients.
Facchini
S
S
Dipartimento di Scienza della Riproduzione e dello Sviluppo, IRCCS Burlo Garofolo, Università di Trieste, Italia.
Candusso
M
M
Martelossi
S
S
Liubich
M
M
Panfili
E
E
Ventura
A
A
D000293:Adolescent; D000328:Adult; D003424:Crohn Disease / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D012008:Recurrence; D012074:Remission Induction; D012449:Safety; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000187:drug effects
D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide