Antirheumatic Disease Therapies for the Treatment of COVID‐19: A Systematic Review and Meta‐Analysis

Abstract

Objective Antirheumatic disease therapies have been used to treat coronavirus disease 2019 (COVID‐19) and its complications. We conducted a systematic review and meta‐analysis to describe the current evidence. Methods A search of published and preprint databases in all languages was performed. Included studies described one or more relevant clinical outcomes in five or more people who were infected with SARS‐CoV‐2 and were treated with antirheumatic disease therapy between 01/01/2019 and 05/29/2020. Pairs of reviewers screened articles and extracted data and assessed risk of bias. A meta‐analysis of effect sizes using the random‐effects models was performed when possible. Results The search identified 3,935 articles, of which 45 were included (4 randomized controlled trials, 29 cohort studies, and 12 case series). All studies evaluated hospitalized patients and 29 out of 45 had been published in a peer‐reviewed journal. In a meta‐analysis of three cohort studies with a low risk of bias, hydroxychloroquine use was not significantly associated with mortality (pooled hazard ratio (HR) 1.41, 95% confidence interval (CI) 0.83‐2.42). In a meta‐analysis of two cohort studies with some concerns/high risk of bias, anakinra use was associated with lower mortality (pooled HR 0.2, 95% CI 0.1‐0.4). Evidence was inconclusive with regard to other antirheumatic disease therapies and the majority of other studies had a high risk of bias. Conclusion In this systematic review and meta‐analysis, hydroxychloroquine use was not associated with benefit or harm with regard to COVID‐19 mortality. The evidence supporting the effect of other antirheumatic disease therapies in COVID‐19 is currently inconclusive.

Hydroxychloroquine for the treatment of COVID-19 and its potential cardiovascular toxicity: Hero or villain?

“…By June 2020, the data from large, well-designed observational studies and emerging evidence from RCTs pointed towards a lack of efficacy for antimalarials in the treatment of COVID-19. The systematic review and meta-analysis by Putman, et al reported data from 45 studies up until May 2020, which included hospitalized COVID-19 patients who were treated with medications commonly used as antirheumatic therapies medication [ 25 ]. When pooled, the three included cohort studies assessing HCQ did not demonstrate an association with COVID-19 mortality.…”

The protective effect of rheumatic disease agents in COVID-19

“…It should be noted that 24% of patients treated with high doses of anakinra developed adverse effects that required discontinuation of the drug, including bacteremia and elevations in liver enzymes [ 7 ]. In a meta-analysis of both studies, anakinra was associated with a significantly lower risk of mortality (pooled HR: 0.2; CI 0.1–0.4) [ 66 ]. Table 2 summarizes the ongoing actively recruiting, phase 3 or 4 clinical trials using anakinra.…”

Prospektive Verlaufsbeobachtung einer universitären Rheumaambulanzkohorte während der ersten Welle der COVID-19-Pandemie

“…Eine COVID-19-Erkrankung unter einer fortgesetzten immunsuppressiven DMARD("disease modifiying antirheumatic drug")-Therapie oder eine COVID-19-Erkrankung in einer Situation, in der wir durch eine Therapiepause möglicherweise einen Schub der Grunderkrankung provozieren, was uns zu einer mittelhoch oder hoch dosierten Glukokortikoidtherapie zwingen würde? In beeindruckender Geschwindigkeit haben zur Klärung die-ser Frage nationale und internationale wissenschaftliche Allianzen Register für rheumatologische Patienten mit SARS-CoV-2-Infektion ins Leben gerufen, und die ersten Publikationen daraus liegen bereits vor [4][5][6][7]. Während die verschiedenen Register den Fokus klar auf die infizierten Patienten richten, lag unser Interesse neben der Inzidenz und dem Verlauf der Infektion in unserer Kohorte auch darauf, wie mit nicht an COVID-19 erkrankten Patienten hinsichtlich der Fortführung ihrer Therapie verfahren wird.…”

“…Eine Therapiereduktion oder -beendigung erfolgte nur bei Patienten mit einem stabilen Krankheitsverlauf. Zudem wurde die fachspezifische Literatur aufmerksam nach Daten bei Rheumapatienten verfolgt und unsere Therapiestrategie entsprechend angepasst [4][5][6]. Results.…”

“…Erste Daten der internationalen Studien der COVID-19 Global Rheumatology Alliance deuten darauf hin, dass ein Fortführen der meisten immunsuppressiven Therapien relativ sicher zu sein scheint [4,5]. Zu beachten gilt, dass v. a. eine mittlere bis hohe Glukokortikoiddosis (äquivalent ≥10 mg Prednisolon/Tag) mit einem höheren Risiko für eine Hospitalisierung aufgrund von COVID-19 assoziiert war, wohingegen DMARDs nicht mit einem erhöhten Risiko assoziiert waren [5].…”