Thalidomide, administered as a
sedative and
antiemetic decades ago, was considered responsible for numerous devastating cases of
birth defects and consequently was banned from markets worldwide. However, the
drug remarkably has resurfaced with promise of immunomodulatory benefit in a wide array of immunologic disorders for which available treatments were limited. It is approved by the Food and Drug Administration for
erythema nodosum leprosum (ENL). Although the relative paucity of
leprosy and ENL worldwide may perceivably limit interest in and knowledge about
thalidomide, increasing numbers of new and potential uses expand its applicability widely beyond ENL.
Thalidomide, an inhibitor of
tumor necrosis factor a, is the best known agent for short-term treatment of ENL
skin manifestations, as well as postremission maintenance
therapy to prevent recurrence. For this indication, it is effective as monotherapy and as part of combination
therapy with
corticosteroids. Studies of
thalidomide in
chronic graft-versus-host disease showed benefit in children and adults as treatment, but not as prophylaxis. The agent has been administered successfully for treatment of
cachexia related to
cancer,
tuberculosis, and human immunodeficiency virus
infection, although evidence of efficacy is inconclusive.
Thalidomide monotherapy effectively induced objective response in trials in patients with both newly diagnosed and advanced or refractory
multiple myeloma. Combination
therapy with
thalidomide and
corticosteroids was also effective in these patients, as well as in treatment of aphthous and genital
ulcers. Limited evidence supports the
drug's benefit in treatment of
Kaposi's sarcoma. Other
thalidomide applications include
Crohn's disease,
rheumatoid arthritis, and
multiple sclerosis.
Somnolence,
constipation, and
rash were the most frequently cited adverse effects in studies, but
thalidomide-induced neuropathy and idiopathic
thromboembolism were critical causes for
drug discontinuation.
Thalidomide is still contraindicated in pregnant women, women of childbearing age, and sexually active men not using
contraception. Clinicians should be conversant with
thalidomide in ENL (its primary application) in the natural course of
leprosy, as well as in the agent's other applications.