Proactive anti-inflammatory therapy with levilimab for patients with COVID-19

Abstract

Objective. To analyze the efficacy of levilimab in patients with COVID-19 to optimize proactive anti-inflammatory therapy. Patients and methods. This single-center retrospective observational controlled study included 75 COVID-19 patients with a mean age of 58.6 years who received intravenous (71%) or subcutaneous (29%) levilimab at a dose of 324 mg on day 9 of the disease [range: 7.0–12.0 days]. Ten patients (14%) additionally received tocilizumab, whereas 14 participants (19%) received only levilimab without dexamethasone. The control group (received no levilimab) included 29 matched patients. The levels of C-reactive protein (CRP), ferritin, fibrinogen, creatine phosphokinase (CPK), D-dimer, as well as lymphocyte and white blood отсутcell (WBC) counts were measured daily. The percentage of lung damage was assessed using computed tomography (CT) at baseline and later in dynamics. The primary endpoint was patient's transfer to the intensive care unit (ICU). Statistical analysis was performed using the Statistica v. 12 software (StatSoft, USA); the risk of transfer to ICU was evaluated using the Kaplan-Meier cumulative proportional risk method and Cox proportional hazards model by calculating relative risks with a 95% confidence interval (RR [CI]). The dynamics of patients' status and its association with the route of levilimab administration was evaluated using a seven-point scale (seven-category scale) approved by the World Health Organization. Results. No lethal outcomes were registered in this study. Levilimab reduced the risk of transfer to the ICU; significant covariates included obesity (RR = 11.09 [1.29–95.72]) and percentage of lung damage on CT scans (RR = 1.06 [1.01–1.13]). The target group for levilimab therapy should include patients with moderate COVID-19 before day 10 of the disease, who have not yet received corticosteroids (CSs), with a maximum body temperature of ≤38.5°C, lung damage <40% on CT at the time of therapy initiation, and CPK <300 U/L. Levilimab therapy is more beneficial for patients with diabetes mellitus, obesity, severe arterial hypertension, and stomach and duodenal ulcers. Intravenous administration of levilimab at a dose of 324 mg is optimal for a reliable prevention of excessive cytokine release. Levilimab demonstrated equivalent positive effects both together with CSs, and when used alone. Levilimab without CSs alleviated hyperglycemia and normalized WBC count. The following laboratory parameters were found to be most important for the decision on levilimab initiation and further control of treatment efficacy: absolute lymphocyte count, CRP, fibrinogen, and CPK. Levels of lactate dehydrogenase, ferritin, platelets, D-dimer did not provide any reliable information on the mitigation of systemic inflammation. Key words: interleukin-6 receptor blockers, levilimab, COVID-19 treatment