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.

COVID-19 in patients with systemic lupus erythematosus: lessons learned from the inflammatory disease

“…As expected, the use of systemic glucocorticoids (sGC) and immunosuppressants such as cyclophosphamide are also associated with a greater risk of herpes zoster and other viral infections. 24,34,35 Cytomegalovirus D 1 1 2 X Xand upper respiratory tract viral infections are common in the SLE population, and may present with severe and atypical manifestations that mimic SLE flares. 28,36 Respiratory infections are one of the most common causes of hospitalization and early mortality in patients with SLE.…”

What's New in the Treatment of Systemic Lupus Erythematosus

“…A meta-analysis of randomized controlled trials of mAbs targeting IFNα or type I IFN receptor subunit 1 (IFNAR) has been recently published (35). Three studies including a total of 927 patients showed that anifrolumab 300 mg was more effective than placebo in achieving SRI-4 and BICLA responses.…”

New possibilities of pharmacotherapy for systemic lupus erythematosus: Prospects for the use of anifrolumab (monoclonal antibodies to type I interferon receptor)

“…Основные результаты, касающиеся эффективности и безопасности АФМ при СКВ, суммированы в серии аналитических обзоров [59,60] и метаанализах РПКИ [61][62][63].…”

“…Данные метаанализа РПКИ MUSE и TULIP, в которые вошли 839 пациентов, получавших АФМ (n=372) и плацебо (n=467) [63], свидетельствуют о более высокой эффективности АФМ по сравнению с плацебо в отношении следующих параметров: эффект по индексу BICLA (отношение шансов (ОШ) -0,44; 95%-й доверительный интервал (ДИ): 0,34-0,59; p<0,00001); снижение ≥50% счета CLASI (ОШ=0,36; 95% ДИ: 0,21-0,60; p=0,0001); эффект по индексу SRI (4) (ОШ=0,52; 95% ДИ: 0,30-0,90; p=0,02). Сходные данные получены в другом метаанализе [61], включавшем 459 пациентов, леченых АФМ, и 468 пациентов, получавших плацебо. Установлено, что лечение АФМ ассоциировалось с увеличением эффективности терапии по индексам SRI (4) (ОШ=1,91; p=0,02), BICLA (ОШ=2,25; p<0,00001), снижением ≥50% по индексу CLASI (ОШ=2,79, p=0,0002 через 12 нед., ОШ=2,61, p=0,004 через 52 нед.)…”