The Role of Thalidomide in the Treatment of Rheumatic Disease

Abstract

Thalidomide was first introduced in 1956 as a sedative hypnotic in Europe and Asia but was soon withdrawn from the market because of its association with severe birth defects. It has experienced a resurgence of interest in recent years as a treatment for inflammatory conditions. Since Jacob Sheskin's linkage of thalidomide with improvement of refractory inflammatory dermatoses, such as erythema nodosum leprosum in the 1960's, more recent work has centered on thalidomide's use in inflammatory rheumatologic conditions. There are varying levels of evidence supporting thalidomide's efficacy in Behcet's disease, refractory oral-genital ulcerations, cutaneous lupus erythematosus, RA, and sarcoidosis, although dosing, clinical response, and frequency of toxicity are variable. Thalidomide seems to have anti-inflammatory, immunomodulatory, and anti-angiogenic properties. It is not clear which of these mechanisms are chiefly responsible for the drug's clinical efficacy. Because of its potential for causing serious and less serious toxic effects, thalidomide should be reserved for the treatment of disease refractory to conventional therapy. In addition to its well known teratogenic potential, thalidomide-induced peripheral neuropathy, in some cases irreversible, has been documented in patients undergoing chronic therapy. Guidelines have been published, and a cooperative effort between the drug manufacturer, Celgene, and the US Food and Drug Administration has resulted in the establishment of a rigorous program governing both the dispensing of thalidomide and monitoring for side effects. Judicious patient selection and intense patient education remain the cornerstone of the safe use of thalidomide.