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

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.

journal_name

Lupus

journal_title

Lupus

authors

Koh JWH,Ng CH,Tay SH

doi

10.1177/0961203320959702

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

1845-1853

issue

14

eissn

0961-2033

issn

1477-0962

journal_volume

29

pub_type

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