A Single Center, Double Blind, Randomized, Placebo-Controlled Trial of Anakinra in Adult Patients with Features of Cytokine Storm Syndrome in COVID-19

Lesley Jackson¹, Randy Cron¹, Nitasha Khullar², Christopher Chapleau³, Dongmei Sun⁴ and Winn Chatham¹, ¹University of Alabama at Birmingham, Birmingham, AL, ²University of Alabama Birmingham, Birmingham, AL, ³UAB Pharmacy, University of Alabama at Birmingham, Birmingham, AL, ⁴Division of Clinical Immunology and Rheumatology, The University of Alabama at Birmingham, Birmingham, AL

Meeting: ACR Convergence 2021

Keywords: Anakinra, clinical trial, COVID-19, macrophage activation syndrome

Session Information

Date: Saturday, November 6, 2021

Session Title: Miscellaneous Rheumatic & Inflammatory Diseases Poster I (0183–0209)

Session Type: Poster Session A

Session Time: 8:30AM-10:30AM

Background/Purpose: Some patients with COVID-19 develop respiratory distress and cytokine storm syndrome (CSS) which is characterized by hyperinflammation and may progress to multi-organ failure. Anakinra is a recombinant interleukin-1 receptor antagonist used to treat some inflammatory disorders and has previously demonstrated mortality benefit in sepsis patients with CSS. Anakinra may play a role in certain patients with COVID-19 to reduce hyperinflammation and improve outcomes. The aim of this study was to assess the efficacy and safety of anakinra when added to standard of care in patients with COVID-19 infection and features of cytokine storm syndrome.

Methods: In this single center, randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov, NCT04362111), adult inpatients were recruited with molecular PCR RNA confirmed SARS-CoV-2 infection, radiographic evidence of COVID-19 pneumonia based on imaging, new or increasing oxygen requirement, ferritin ≥700 ng/ml, and any three of the following: D-dimer ≥500 ng/ml, platelet count < 130,000/mm³, white blood cell count < 3500/mm³ or lymphocyte count < 1000/mm³, AST or ALT >2X the upper limit of normal (ULN), LDH >2X the ULN, C-reactive protein >100 mg/L. Eligible patients were randomly assigned (1:1) to standard of care (SoC) plus anakinra (100 mg subcutaneous every 6 hours for 10 days) or SoC plus placebo. All received dexamethasone. Primary outcome was survival and discharge from the hospital without the need for intubation/mechanical ventilation at day 10. All analyses were done on a modified intention-to-treat basis.

Results: Between August 5, 2020 and January 2, 2021, 32 patients (235 screened) were recruited: 15 assigned to the anakinra group and 17 to placebo group. Two patients in the placebo group withdrew in the initial 48 hours and were excluded from analysis. Mean age was 63 (SD 10.3), 20 (66.7%) participants were men, and 20 (66.7%) were Caucasian. At day 10, 1 (6.7%) patient in the anakinra group had died and 2 (13.3%) patients in the placebo group had died (p=1.0). At hospital discharge, 4 (26.7%) patients in the anakinra group and 4 (26.7%) patients in the usual care group had died. Confirmed microbial infections occurred in 4 patients in the anakinra group and 2 in the placebo group (p=0.7).

Conclusion: Anakinra added to dexamethasone did not significantly impact outcomes in this study of patients with clinical laboratory features of early CSS and mild-to-moderate COVID-19 pneumonia. Additional studies are needed to assess the efficacy and optimal dosing duration of anakinra in patients with more severe COVID-19.

Table 1. Outcomes with anakinra verses placebo, modified intent to treat analysis; N (%) unless otherwise stated.
* P values < 0.05

Table 2. Estimation of anakinra effect on the composite of death from any cause or need for invasive mechanical ventilation, after adjustment for potential confounding factors, using a multivariable Cox proportional hazards model.

Figure 1. Kaplan Meier Curve demonstrating survival according to treatment with anakinra and placebo groups.

Disclosures: L. Jackson, None; R. Cron, SOBI, 1, 2, 5, 6, Pfizer, 1, 5, Novartis, 2, Sironax, 2; N. Khullar, None; C. Chapleau, None; D. Sun, None; W. Chatham, None.

To cite this abstract in AMA style:

Jackson L, Cron R, Khullar N, Chapleau C, Sun D, Chatham W. A Single Center, Double Blind, Randomized, Placebo-Controlled Trial of Anakinra in Adult Patients with Features of Cytokine Storm Syndrome in COVID-19 [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/a-single-center-double-blind-randomized-placebo-controlled-trial-of-anakinra-in-adult-patients-with-features-of-cytokine-storm-syndrome-in-covid-19/. Accessed May 16, 2022.

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