Thalidomide « the First Biologic Drug »

Thalidomide and Analogues: Potential for Immunomodulation for Inflammatory and Neoplastic Dermatologic Disorders.

Ladizinski B, Shannon E, Sanchez M, Levis W.

J. Drugs Dermatol. 2010; 9 (7): 814-826.

• Thalidomide was introduced in 1953 and was prescribed over-the-counter against nausea in pregnant women. It resulted in serious malformations and the drug was rapidly banned.
• Because t of this sad story, we have mainly focused on the side effects of the drug such as demyelinizing polyneuropathy and teratogenic effects. This the drug is now difficult to obtain (in France for example, it is only delivered on a hospital prescription).
• This article explores in detail the mecanisms of action, which consists of the modulation of the activation of lymphocytes T, which results in the liberation of the chemokine TNF alpha. It doesn’t seem so different than ustekimumab, which inhibits the activation of the T lymphocyte, by blocking Il-12 and Il-23 action. More anectdotically other biologics act by linking TNF-alpha (such as efalizumab which was banned from usage in Europe because its dangerous side effect on the nervous system: progressive multifocal leukoencephalopathy).
• The article also shows dermatologic indications where thalidomide is used:

1. Erythema nodosum leprosum
2. Behcet’s disease
3. Lupus erythematosus
4. Sarcoidosis
5. Cutaneous T-cell lymphoma (Mycosis fungoides)
6. Melanoma
7. Actinic prurigo, Adult-onset Langerhans histiocytosis, aphtous stomatitis, erythema multiforme, familial Mediterranean fever, graft-versus-host disease, lichen planus, Kaposi’s sarcoma, Merkelsson-Rosenthal’s syndrome, porphyria cutanea tarda, prurigo nodularis, pyoderma gangrenosum, Schnitzler’s syndrome, lymphocytic infiltrate of Jessner Kanof, uremic pruritus.

• The article also presents potential future indications:

1. Allergic contact dermatitis
2. Atopic dermatitis
3. Psoriasis (..like the biologic drugs)

• Like thalidomide, biologics have a broad mechanism of action on the process of inflammation. We can imagine, that like the former, potentially serious side effects could be discovered (such as that which has already be discovered for efalizumab). However, such findings must not stop the progress of Science, that is the discovery of new therapeutical indications. As F.D Roosevelt said so correctly: “The only thing we have to fear is fear itself.”