Thalidomide treatment for refractory Crohn's disease: a review of the history, pharmacological mechanisms and clinical literature

Abstract

Several recent case reports and clinical trials have demonstrated that thalidomide is emerging as an efficacious alternative in the treatment of selected patients with refractory Crohn's disease. The effects of thalidomide are at least partly mediated by down-regulation of tumour necrosis factor (TNF)-α, a potent proinflammatory cytokine. However, thalidomide is also known to inhibit angiogenesis, and it has several other well-described immunomodulatory properties. Clinical studies have confirmed that previously refractory Crohn's disease patients respond to thalidomide, and many enter clinical remission. Efficacy usually occurs within 4 weeks. Thalidomide also has steroid-sparing properties, and it is particularly useful in treating oral and fistulous complications of Crohn's disease. Although it is usually tolerable, careful monitoring is recommended to prevent toxicities, such as birth defects and peripheral neuropathy. This review provides a detailed summary of the literature to date on the use of thalidomide treatment for Crohn's disease. Special attention is directed towards its history, mechanisms, and proposed role. The recent development of thalidomide analogues is also discussed briefly.