Thalidomide for Erythema Nodosum Leprosum and Other Applications

Mark C. Okafor, Pharm.D.


Pharmacotherapy. 2003;23(4) 

In This Article

Abstract and Introduction

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 , 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.

Thalidomide, an agent rejected for its induction of birth defects in the 1950s and 1960s, has found new life with new applications. Before its withdrawal, it had been administered as a sedative and antiemetic in pregnant women. The United States was spared from its ill effects, since it awaited Food and Drug Administration (FDA) approval while a definite link was established, in 1961, between the drug and reported cases of birth defects in many other countries.[1] This caused its removal from the market in Britain, Germany, and most of the world. In 1998, however, after years of evidence of benefit in leprosy, the FDA approved the drug for treatment of cutaneous lesions associated with erythema nodosum leprosum (ENL).[2] The drug also has been employed successfully for other investigational disorders including human immunodeficiency virus (HIV) infection, cancer-related cachexia, multiple myeloma, Kaposi's sarcoma, oral ulcers, and chronic graft-versus-host disease.[3]

To determine resources regarding the agent's various applications, a thorough search of MEDLINE from January 1966-December 2002 was conducted. This led to evaluation of research, clinical trial literature, and pertinent abstracts on thalidomide therapy for each listed condition.


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