Biologics targeting type I interferons in SLE: A meta-analysis and systematic review of randomised controlled trials. (December 2020)

• Record Type: Journal Article
• Authors: Koh, Jeffery Wei Heng; Ng, Cheng Han; Tay, Sen Hee
• Is Part Of: Lupus. Volume 29:Number 14(2020)
• Page Start: 1845
• Page End: 1853
• Publication Date: 2020-12
• Subjects: Systemic lupus erythematosus -- interferon type I -- anifrolumab -- meta-analysis; Systemic lupus erythematosus -- Periodicals; 616.772005
• DOI: 10.1177/0961203320959702
• Languages: English
• ISSNs: 0961-2033

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 IFNα 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 IFNα or IFNAR. Methods: A search was done using Medline, Embase and ClinicalTrials.gov for biologics targeting IFNα 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 IFNα 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.