Efficacy and safety of anakinra in adults presenting deteriorating respiratory symptoms from COVID-19: A randomized controlled trial

Abstract

Objective We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. Methods In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. Results Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference—21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). Conclusion This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

HIV and COVID-19 Co-Infection: Epidemiology, Clinical Characteristics, and Treatment

“…There exist several trials investigating its potential use as an adjunctive medication for COVID-19 infection, with conflicting results. One major positive blinded trial from Greece showed that the use of anakinra among patients with suPAR ≥ 6 mg/dl (a surrogate marker of inflammation) cut mortality in half [ 136 ]. The generalizability of the results is limited due to the use of a not widely available biomarker, although the authors also suggested that a score using lymphocytes and ferritin levels could be used in its place.…”

“…The generalizability of the results is limited due to the use of a not widely available biomarker, although the authors also suggested that a score using lymphocytes and ferritin levels could be used in its place. On the other hand, a multi-center open-label French study was halted prematurely due to safety concerns after an interim analysis revealed that anakinra use was associated with worse prognosis on day 14 (treatment success 70% vs. 91%, OR 0.23, 95%CI 0.06 to 0.91, p = 0.027) and a marginally non-significant increase in 28-day mortality [ 136 ]. A Cochrane meta-analysis included four anakinra RCTs and was not able to find any significant effect of anakinra on 28-day mortality or disease progression, albeit with low or very low level of certainty [ 137 ].…”

Anti-Interleukins for Severe Coronavirus Disease-2019: Hype or Hope?

“… 16 A recently published RCT also failed to document any treatment benefit with anakinra among subjects hospitalised due to severe COVID-19. 17 Similarly, in the formerly published DAWn-Antico study, anakinra treatment in patients with severe COVID-19 and hyper-inflammation did not result in significant improvement in efficacy outcomes, including COVID-19 related mortality. 18 …”

Evaluation of anakinra in the management of patients with COVID-19 infection: A randomized clinical trial

“…However, such observational findings required extensive assessments in well-conducted randomized clinical trials to verify the reported outcomes ( Cavalli et al, 2020 ; Langer-Gould et al, 2020 ). Later, few small randomized trials and meta-analyses were conducted to assess the benefit of anakinra in COVID-19 patients with inconclusive outcomes ( Balkhair et al, 2021 ; Barkas et al, 2021 ; Declercq et al, 2021 ; Audemard-Verger et al, 2022 ; Kharazmi et al, 2022 ; Malık et al, 2022 ; Naveed et al, 2022 ). As in selected patients with severe COVID-19 pneumonia, anakinra has demonstrated beneficial outcomes, while it did not show a significant benefit in other patient groups ( Balkhair et al, 2021 ; Barkas et al, 2021 ; Declercq et al, 2021 ; Audemard-Verger et al, 2022 ; Kharazmi et al, 2022 ; Malık et al, 2022 ; Naveed et al, 2022 ).…”

“…Later, few small randomized trials and meta-analyses were conducted to assess the benefit of anakinra in COVID-19 patients with inconclusive outcomes ( Balkhair et al, 2021 ; Barkas et al, 2021 ; Declercq et al, 2021 ; Audemard-Verger et al, 2022 ; Kharazmi et al, 2022 ; Malık et al, 2022 ; Naveed et al, 2022 ). As in selected patients with severe COVID-19 pneumonia, anakinra has demonstrated beneficial outcomes, while it did not show a significant benefit in other patient groups ( Balkhair et al, 2021 ; Barkas et al, 2021 ; Declercq et al, 2021 ; Audemard-Verger et al, 2022 ; Kharazmi et al, 2022 ; Malık et al, 2022 ; Naveed et al, 2022 ). The presented open-label randomized clinical trial aimed to explore the safety and efficacy of anakinra in addition to standard of care (SOC) compared to SOC alone in patients with confirmed COVID-19 infection with respiratory distress and evidence of cytokine release syndrome.…”