Anakinra for the treatment of COVID-19 patients: a systematic review and meta-analysis

Abstract

Background At the end of 2021, the European Medicines Agency (EMA) expanded its approval for the recombinant human interleukin-1 (IL-1) receptor antagonist Anakinra for the treatment of COVID-19 patients with elevated soluble urokinase plasminogen activator receptor (suPAR). However, the role of Anakinra in COVID-19 remains unanswered, especially in patients receiving different forms of respiratory support. Therefore, the objective of this systematic review is to assess the safety and effects of Anakinra compared to placebo or standard care alone on clinical outcomes in adult hospitalized patients with SARS-CoV-2 infection. Methods We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, medRxiv, and the Cochrane Central Register of Controlled Trials (CCSR)) and the WHO COVID-19 Global literature on coronavirus disease database to identify completed and ongoing studies from inception of each database to December 13, 2021. Since then, we monitored new published studies weekly up to June 30, 2022 using the CCSR. We included RCTs comparing treatment with Anakinra to placebo or standard care alone in adult hospitalized patients with SARS-CoV-2 infection. Results We included five RCTs with 1,627 patients (nAnakinra = 888, ncontrol = 739, mean age 59.63 years, 64% male). Random-effects meta-analysis was used to pool data. We found that Anakinra makes little or no difference to all-cause mortality at up to day 28 compared to placebo or standard care alone (RR 0.96, 95% CI 0.64–1.45; RD 9 fewer per 1000, 95% CI 84 fewer to 104 more; 4 studies, 1593 participants; I2 = 49%; low certainty of evidence). Conclusions Anakinra has no effect on adult hospitalized patients with SARS-CoV-2 infection regarding mortality, clinical improvement and worsening as well as on safety outcomes compared to placebo or standard care alone. Trial Registration: PROSPERO Registration Number: CRD42021257552.

Use of high-dose steroid therapy: addition of anakinra in the treatment of severe COVID-19

“…In a systematic review in which the efficacy of anakinra was evaluated in hospitalized patients with COVID-19, mortality did not decrease compared to placebo and standard treatment groups in patients receiving anakinra 12 . In another study, clinical outcomes were not better in patients receiving anakinra than the standard care group and placebo group 13 .…”

Interleukin-1 Blockers: A Paradigm Shift in the Treatment of Recurrent Pericarditis

“…Following the results of the SAVE-MORE trial, anakinra was approved for the treatment of COVID-19 in adult patients with pneumonia requiring supplemental oxygen and who are at risk of developing severe respiratory failure, as determined by elevated suPAR (soluble urokinase plasminogen activator receptor) at values > 6 ng/mL, providing a potential benefit in the early stages of SARS-CoV-2 infection [ 105 ]. However, in more recent systematic reviews and meta-analyses, anakinra and canakinumab exhibited little to no effect on mortality, safety outcomes, and disease progression in adult hospitalized patients with SARS-CoV-2 infection [ 106 , 107 ]. Given that patients with autoinflammatory conditions are at increased risk for relapse after discontinuation of IL-1 inhibitors, the authors would recommend conditionally continuing anakinra in patients contracting COVID-19 while on long-term treatment.…”

Anakinra authorized to treat severe coronavirus disease 2019; Sepsis breakthrough or time to reflect?

“…This design employs external deliberate specific intervention on a proposed cause of disease (excessive IL-1β for the case of anakinra trials) to assess effect on outcome or clinical course of COVID-19. Two recent systematic reviews and meta-analyses including only RCTs in adults hospitalized with COVID-19 evaluated anakinra therapy with study accrual extending to 2022 and no language restriction ( Dahms et al, 2023 ; Shang et al, 2023 ). These 2 analyses pooled data from the same 5 anakinra RCTs, and the SAVE-MORE study was included in both reports.…”