Biologics targeting type I interferons in SLE: A meta-analysis and systematic review of randomised controlled trials.

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Koh JWH, Ng CH, Tay SH

Biologics targeting type I interferons in SLE: A meta-analysis and systematic review of randomised controlled trials.

Lupus. 2020 Dec;29(14):1845-1853. doi: 10.1177/0961203320959702. Epub 2020 Sep 22.

PubMed ID
32960720 [ View in PubMed
]
Abstract

OBJECTIVE: The feed-forward loop of type I interferons (IFNs) production and subsequent immunopathology of systemic lupus erythematosus (SLE) has been hypothesised to be disrupted with inhibition of IFNalpha or type I IFN receptor subunit 1 (IFNAR). This systematic review and meta-analysis present the treatment efficacy and safety profile of monoclonal antibodies inhibiting IFNalpha or IFNAR. METHODS: A search was done using Medline, Embase and ClinicalTrials.gov for biologics targeting IFNalpha or IFNAR in SLE up to 3 Jan 2020. For the meta-analysis, analyses of binary variables were pooled using odds ratio (OR) with the Mantel Haenszel model. RESULTS: Anifrolumab 300 mg (n = 3 studies, 927 patients) was more effective than placebo in achieving SRI(4) (pooled OR = 1.91, CI 1.11-3.28, P = 0.02) and BICLA response (pooled OR = 2.25, CI 1.72-2.95, P < 0.00001). In SLE patients with high type I IFN gene signature, SRI(4) response was not achieved with anifrolumab in 2 studies, 450 patients. Treatment with IFNalpha and IFNAR inhibitors (n = 7 studies, 1590 patients) increased the risk of herpes zoster infection (pooled OR = 3.72, CI 1.88-7.39, P = 0.0002), upper respiratory tract infections, nasopharyngitis and bronchitis. CONCLUSION: This meta-analysis substantiates IFNAR as a therapeutic target in SLE. Inhibition of type I IFNs predisposes to herpes zoster and other viral infections.

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