Thalidomide

Thalidomide is a biologic response modifier with an increasing number of applications in severe inflammatory, immune, or dermatologic diseases. It is anti-inflammatory, anti-angiogenic, and immulomodulatory. Originally introduced as a sedative in the 1950s, it causes extreme fetal malformations or fetal death, and was unavailable for many years. It was reintroduced for the narrow indication of preventing and treating severe skin reactions in leprosy, and for multiple myeloma.

Thalidomide is absolutely contraindicated in pregnancy. Female patients who receive it must use two forms of contraception.

Indications

Erythema Nodosum Leprosum, Multiple Myeloma, Prevention of Erythema Nodosum Leprosum

Thalidomide also has been designated an orphan drug by FDA for treatment of wasting syndrome associated with human immunodeficiency virus (HIV) infection†; prevention and treatment of severe recurrent aphthous stomatitis in severely, terminally immunocompromised patients†; prevention and treatment of graft-versus-host disease in patients receiving bone marrow transplantation†; treatment of clinical manifestations of mycobacterial infection caused by Mycobacterium tuberculosis and nontuberculous mycobacteria†; treatment of Crohn’s disease†; and treatment of primary brain tumors†. In addition, thalidomide has been used for the treatment of a variety of inflammatory and/or dermatologic disorders, treatment of various HIV-associated conditions, and treatment of various malignancies. Use of thalidomide may not limit disease progression and/or death.

Pharmacology

While all of its mechanisms are not fully understood, its functions include:

• immunomodulator for tumor necrosis factor-alpha
• costimulatory or adjuvant effect on T-lymphocytes resulting in increased T-cell proliferation and increased production of interleukin-2 and interferon gamma
• modulation of leukocyte migration and chemotaxis.
• Possible suppression of macrophage involvement of prostaglandin synthesis and modulation of interleukin-10 and interleukin-12 production by peripheral blood monocytes.

While its anti-inflammatory and immunomodulatory effects are complex, they appear different from those of other agents, including corticosteroids, cyclosporin (e.g., cyclosporine) or macrolide (e.g., tacrolimus) immunosuppressants, pentoxifylline, immunosuppressive purine analogs (e.g. azathioprine) and purine metabolism inhibitors (e.g., mycophenolic acid), and nonsteroidal anti-inflammatory agents.

It does not appear to interfere with antimicrobial defense mechanisms, lyphocyte proliferation, granuloma formation, and delayed hypersensitivity reactions.