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New immune modulatory drugs for systemic lupus erythematosus—what can we expect?

Nature Clinical Practice Rheumatology volume 2, pages 638–639 (2006)Cite this article

Systemic lupus erythematosus (SLE) is a disease triggered by environmental factors in individuals with a genetically predetermined alteration of the threshold for induction or maintenance of immune tolerance. In mice, SLE can result from many different genetic defects that affect tolerance, including increased antigen load, alterations in lymphocyte signaling or death, increased co-stimulation, and inappropriate cytokine production.1 The immune-system activation pathways that initiate SLE might not always perpetuate disease, however, and factors that protect against disease initiation might be pathogenic during the effector phase. Furthermore, inflammatory environments can alter signaling cascades or provide redundant survival signals.2 Thus, targeting a single pathway might not be sufficient to induce remission once inflammation is present.

New immunomodulatory therapies for SLE target pathways associated with immune activation, including B-cell survival (BAFF blockade) or signaling (anti-CD22), T-cell co-stimulation (CTLA4Ig), and inflammatory cytokines (interferon [IFN]-α, tumor necrosis factor [TNF], or interleukin [IL]-6 blockade). Given the heterogeneity of the disease, it can be expected that each approach will only be effective in specific subsets of patients. The challenge, therefore, is to determine the mechanism of action of each drug and identify the appropriate patient population, in order to design clinical trials that most accurately test therapeutic efficacy.

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  1. Professor in the Departments of Medicine and Microbiology at Columbia University, New York, NY, USA

    Anne Davidson

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  1. Anne Davidson
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Correspondence to Anne Davidson.

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Competing interests

A Davidson is a Consultant for Abbott Pharmaceuticals. She has participated in clinical trials of CTLA4Ig. Dr Davidson has received NIH grant support to study STLA4Ig in murine SLE.

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Davidson, A. New immune modulatory drugs for systemic lupus erythematosus—what can we expect?. Nat Rev Rheumatol 2, 638–639 (2006). https://doi.org/10.1038/ncprheum0301

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