Thalidomide and Lenalidomide for Refractory Systemic/Cutaneous Lupus Erythematosus Treatment

A Narrative Review of Literature for Clinical Practice

Emily Figueiredo Neves Yuki, MD; Clovis A. Silva, MD, PhD; Nadia E. Aikawa, MD, PhD; Ricardo Romiti, MD, PhD; Carlos Otto Heise, MD, PhD; Eloisa Bonfa, MD, PhD; Sandra Gofinet Pasoto, MD, PhD

Disclosures

J Clin Rheumatol. 2021;27(6):248-259. 

In This Article

Thalidomide

Mechanisms of Action

Thalidomide is highly effective in controlling cutaneous lupus activity, and clinical response is very quick.[27,28] Therefore, it is an important therapeutic option for refractory SLE/CLE patients without formal contraindication, requiring strict contraception to avoid teratogenesis.[29] The main proposed mechanisms of action for the effect of thalidomide in cutaneous lupus treatment include (1) modification of integrin receptors, (2) inhibition of tumor necrosis factor α (TNF-α) production, (3) inhibition of angiogenesis, and (4) reduction of phagocytosis by polymorphonuclear cells.[30] Thalidomide acts primarily by reducing the synthesis of TNF-α and modifying the expression of adhesion molecules on the surface of endothelial cells.[29,31] Reinforcing this possible mechanism of action, it has been demonstrated that TNF-α and type 1 interferon (IFN-1) are increased in cutaneous lupus lesions.[32] Indeed, some studies have shown that plasma levels of TNF-α and IFN-1 are higher in SLE patients than those in the normal population, as well as plasma levels of TNF-α were elevated in patients with active SLE compared with those with a quiescent disease.[33] Dall'era et al.[34] also reported a positive correlation of plasma IFN-1 levels with SLE cutaneous activity and also with Systemic Lupus Erythematosus Disease Activity Index values.[34] Thalidomide seems to inhibit keratinocyte apoptosis induced by ultraviolet B,[35] which is another relevant aspect in the pathogenesis of CLE.[36]

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