Novel treatments for systemic lupus erythematosus - PubMed (original) (raw)

Novel treatments for systemic lupus erythematosus

Wen Xiong et al. Ther Adv Musculoskelet Dis. 2011 Oct.

Abstract

There are many new therapeutic directions for the disease systemic lupus erythematosus (SLE). Despite this, the US Food and Drug Administration (FDA) has approved only one biological agent and it involves B cells, now thought to play a significant role in the pathogenesis of SLE. The name of the drug is belimumab, which is an agent that removes the B-cell cytokine called B lymphocyte stimulation factor (BLyS). Rituximab did not achieve its primary endpoints, even though the consensus is that it may be effective in some forms of SLE including renal disease. The anticytokine therapies against interleukin (IL)-6, IL-10, IL-17 and tumor necrosis factor (TNF) are effective in their own ways and phase II and III trials are in progress. Of particular interest to immunologists are the anti-interferon alpha and gamma drugs, which show promise in the animal models. Modulation of costimulatory molecules; specifically, the anti CD40, CTLA-***Ig and ICOS/B7RP blockade agents offer possibilities for the future using new pathways heretofore limited to rheumatoid arthritis. Finally, the use of tyrosine kinase inhibitors is another direction that has been successful in the inhibition of SLE in the murine model; early trials in human SLE have begun.

Keywords: B cells; anticytokine therapies; biologics; lupus; systemic lupus erythematosus.

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Conflict of interest statement

The authors declare no conflicts of interest in preparing this article.

Figures

Figure 1.

Figure 1.

Mechanism of target biological therapies in SLE. Ag: antigen; Ab: antibody; Anti-IL-6: anti-interleukin-6; Anti-IL-10: anti-interleukin-10; Anti-IL-17: anti-interleukin-17; anti-TNF: anti-tumor necrosis factor; anti-IFN-a: anti-interferon-a; Anti-IFN-r: anti-interferon-r; TLR: toll like receptor; CTLA4-Ig: cytotoxic T lymphocyte activator 4-immunoglobulin; ICOS: Inducible co-stimulator; B7RP-1: B7-related protein-1; BAFF-R: B-cell activating factor; TACI: transmembrane activator and calcium-modulating cyclophilin ligand interactor; BCMA: B cell maturation antigen; SyK: Spleen tyrosine kinase. Adapted by the author and reprinted with permission from Klippel, J. H. et al. Primer on the Rheumatic Diseases. 13th ed. pp. 335.

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