Thalidomide in gastrointestinal disorders.
Thalidomide was originally marketed as a sedative, but was removed from the market in 1961 after it was associated with an epidemic of severe birth defects. Subsequently, it has been shown to have therapeutic efficacy in a number of the gastrointestinal tract conditions characterised by immune dysregulation. The exact mechanism of the immunosuppressive effects of thalidomide is unknown; proposed mechanisms include inhibition of tumour necrosis factor alpha release and inhibition of angiogenesis. In chronic graft versus host disease, use of high dose thalidomide (1200 mg/day) may bring about a response in 20% of patients with refractory disease. Thalidomide 200 mg/day helps eradicate ulcers in 50% of patients with HIV-associated oral aphthous ulceration. In Behçet's disease, thalidomide 100 to 300 mg/day can decrease the number of mucocutaneous ulcers, although full remission occurs in less than 20% of patients. In Crohn's disease, thalidomide 50 to 300 mg/day may decrease the severity of mucosal disease and prompt closure of fistulae. Patients to be placed on thalidomide therapy must practice either abstinence or strict birth control; women must undergo regular pregnancy testing and utilise 2 forms of contraception. Other adverse effects include sedation (present in nearly all patients), symptomatic neuropathy (present in approximately 20%), and skin rashes. Given the potential toxicity, thalidomide use should generally be limited to clinical protocols with institutional review board oversight.
Bousvaros
A
A
Division of Gastroenterology, Boston Children's Hospital/Harvard Medical School, Massachusetts 02115, USA. bousvaros@a1.tch.harvard.edu
Mueller
B
B
D001528:Behcet Syndrome / Q000188:drug therapy; D002448:Cell Adhesion / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000188:drug therapy; D003424:Crohn Disease / Q000188:drug therapy; D005767:Gastrointestinal Diseases / Q000188:drug therapy*; D006086:Graft vs Host Disease / Q000188:drug therapy; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013792:Thalidomide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D013792:Thalidomide