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Thalidomide for rheumatic disease: the best of both worlds?

Nature Clinical Practice Rheumatology volume 3, pages 308–309 (2007)Cite this article

As rheumatologists, each of us is keenly aware of the fine balance between therapeutic suppression of inflammatory reactions to prevent tissue damage and the corresponding increased risk of severe infection. A variety of biologic agents are now available that interfere with tumor necrosis factor (TNF) or interleukin (IL)-1β, and additional agents that block IL-6 are likely to be available in the near future. Each of these agents is associated with a dramatic reduction in the inflammatory response, but each has also been associated with an increased risk of infection.1,2 In addition, although it is clear that TNF and IL-1β act in concert in vivo, the use of combinations of biologics to block both of these cytokines leads to an unacceptable incidence of infection in treated patients. Because the biologic agents must be administered parenterally, emphasis has been placed on agents with a long half-life to minimize the inconvenience of administration. When patients treated with these agents develop infections, however, the period of vulnerability is prolonged by the long half-lives. It would, therefore, be very positive for both patients and clinicians if there was a readily available oral agent that blocked TNF, IL-1β and IL-6 with a short half-life that could be safely used in patients at risk of serious infection.

Although thalidomide was widely disparaged after recognition of its teratogenicity,3 its immunomodulatory activities have become increasingly apparent.4 These effects were first observed following the discovery that thalidomide alleviated the symptoms of patients with erythema nodosum leprosum in 1965.3,5 Interest in the immunomodulatory activities of thalidomide increased dramatically when it was found to be beneficial for complications of HIV without an increased risk of infections.6,7 Although at present thalidomide is approved by the FDA only for use in the treatment of multiple myeloma and erythema nodosum leprosum, reports in the literature indicate that thalidomide is effective for a wide variety of immune-mediated conditions without an evident increase in the risk of infection.4

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  1. Division of Pediatric Rheumatology, Hospital for Special Surgery, 535 E 70 Street, New York, NY 10021, USA goldscout@aol.com

Authors and Affiliations

  1. TJA Lehman is Chief of the Division of Pediatric Rheumatology at the Hospital for Special Surgery and Professor of Clinical Pediatrics at the Weill Medical College of Cornell University, New York, NY, USA.,

    Thomas JA Lehman

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Dr. Lehman is the past recipient of a research grant from Celgene.

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Lehman, T. Thalidomide for rheumatic disease: the best of both worlds?. Nat Rev Rheumatol 3, 308–309 (2007). https://doi.org/10.1038/ncprheum0504

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