Early studies on the safety and efficacy of thalidomide for symptomatic inflammatory bowel disease.

Abstract

Thalidomide is clinically effective in the treatment of graft versus host disease in bone marrow transplantation and aphthous ulceration in HIV infection. It appears to exert a selective effect on tumor necrosis factor-alpha (TNF-alpha) production. Tumor necrosis factor-alpha is implicated in the pathogenesis of inflammatory bowel disease (IBD). The aim of this study was to assess the efficacy and safety of thalidomide in symptomatic IBD. Eleven patients (nine males, mean age 33 years, range 20-77 years) with chronic inflammatory bowel disease (six Crohn's disease (CD), four ulcerative colitis (UC), one indeterminate colitis (IC)) who were symptomatic despite standard medical therapy were administered a daily dose of thalidomide for 12 weeks in an open-labeled protocol. Their response was assessed by using clinical, colonoscopic, histological, and immunological methods. Two patients withdrew at 3 weeks because of mood disturbances. Of the remaining nine patients, eight (five CD, two UC and one IC) had a marked clinical response, while one patient with CD had no response. The mean stool frequency decreased from 4.3 to 2.3 per day (P = 0.0012), and the stool consistency increased from 2.1 to 1.2 (P = 0.02). The mean Crohn's Disease Activity Index decreased from 117 to 48 (P = 0.0008). Endoscopic inflammatory and histological grade, C-reactive protein and erythrocyte sedimentation rate (ESR) all decreased significantly (P = 0.011, P = 0.03, P = 0.023 and P = 0.044, respectively). However, the serum TNF-alpha levels did not change. Side-effects included mild sedation, xerostomia and skin dryness in all, constipation in three, and minor abnormalities in nerve conduction in one patient. These data strongly suggest that thalidomide is an effective short-term treatment for symptomatic IBD.