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Interferon-directed therapies for the treatment of systemic lupus erythematosus: a critical update

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Abstract

The interferon (IFN) pathway, especially type I IFN, plays a critical role in the immunopathogenesis of systemic lupus erythematosus (SLE). We have gained significant insights into this pathway over the past two decades, including a better understanding of the key mediators of inflammation upstream and downstream of type I IFN. This has led to the identification of multiple potential targets for the treatment of SLE, for which a significant unmet need remains due to the failure of many patients to adequately respond to standard-of-care medications. Unfortunately, most new therapies in SLE have disappointed in preclinical or clinical trials to date, including a number that target type I IFN. Nevertheless, several IFN-directed therapies aimed at specific steps within this immunologic pathway have recently shown promise, and additional agents are in the treatment pipeline. In this review, we focus on the results of key therapeutic studies targeting the type I IFN pathway and discuss the future state of IFN-blockade in SLE.

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Authors and Affiliations

  1. Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA, USA

    Yashaar Chaichian & Vibeke Strand

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  1. Yashaar Chaichian
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  2. Vibeke Strand
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Correspondence to Yashaar Chaichian.

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YC has received support from AMPEL BioSolutions, Gilead Sciences, the Lupus Research Alliance, Pfizer, Amgen, and Lilly to conduct clinical research, and has served in an advisory board role for GSK. VS has received consulting fees or honoraria from AbbVie, Amgen, Arena, Asana, AstraZeneca, BMS, Boehringer Ingelheim, Celltrion, EMD Serono, Equillium, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Janssen, Kypha, Lilly, Merck, MyoKardia, Novartis, Pfizer, Regeneron, Samsung Bioepis, Sandoz, Sanofi, and UCB.

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Key points

• Type I interferon (IFN) is a key mediator of systemic lupus erythematosus (SLE) pathogenesis.

• In recognition of its importance in SLE, multiple therapies targeted to the type I IFN pathway have been or are being studied in randomized controlled trials (RCTs) or are currently in development.

• Despite notable failures emblematic of SLE RCTs in general, several promising type I IFN-directed therapies have emerged and provide hope that additional effective management options for patients with SLE will be forthcoming.

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Chaichian, Y., Strand, V. Interferon-directed therapies for the treatment of systemic lupus erythematosus: a critical update. Clin Rheumatol 40, 3027–3037 (2021). https://doi.org/10.1007/s10067-020-05526-1

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  • DOI: https://doi.org/10.1007/s10067-020-05526-1

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