Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: a retrospective cohort study
Authors: Bryushkova E.A. , Skatova V.D. , Mutovina Z.Y. , Zagrebneva A.I. , Fomina D.S. , Kruglova T.S. , Akopyan A. , Strazhesko I.D. , Lukyanov S. , Tkacheva O.N. , Lysenko M.A. , Chudakov D.M. 
Published: April 2022

Background

The aim of the study was to assess inflammatory markers and clinical outcomes in adult patients admitted to hospital with mild-to-moderate COVID-19 and treated with targeted immunosuppressive therapy using anti-IL-17A (netakimab), anti-IL-6R (tocilizumab), or JAK1/JAK2 inhibitor (baricitinib) or with standard-of-care (SOC) therapy.

Methods

The retrospective, observational cohort study included 154 adults hospitalized between February and August, 2020 with RT-PCR-confirmed SARS-CoV-2 with National Early Warning Score2 (NEWS2) < 7 and C-reactive protein (CRP) levels ≤ 140 mg/L on the day of the start of the therapy or observation. Patients were divided into the following groups: I) 4 mg baricitinib, 1 or 2 times a day for an average of 5 days (n = 38); II) 120 mg netakimab, one dose (n = 48); III) 400 mg tocilizumab, one dose (n = 34), IV) SOC: hydroxychloroquine, antiviral, antibacterial, anticoagulant, and dexamethasone (n = 34).

Findings

CRP levels significantly decreased after 72 h in the tocilizumab (p = 1 × 10−5) and netakimab (p = 8 × 10−4) groups and remained low after 120 h. The effect was stronger with tocilizumab compared to other groups (p = 0.028). A significant decrease in lactate dehydrogenase (LDH) levels was observed 72 h after netakimab therapy (p = 0.029). NEWS2 scores significantly improved 72 h after tocilizumab (p = 6.8 × 10−5) and netakimab (p = 0.01) therapy, and 120 h after the start of tocilizumab (p = 8.6 × 10−5), netakimab (p = 0.001), or baricitinib (p = 4.6 × 10−4) therapy, but not in the SOC group. Blood neutrophil counts (p = 6.4 × 10−4) and neutrophil-to-lymphocyte ratios (p = 0.006) significantly increased 72 h after netakimab therapy and remained high after 120 h. The percentage of patients discharged 5-7 days after the start of therapy was higher in the tocilizumab (44.1%) and netakimab (41.7%) groups than in the baricitinib (31.6%) and SOC (23.5%) groups. Compared to SOC (3/34, 8.8%), mortality was lower in netakimab (0/48, 0%, RR=0.1 (95% CI: 0.0054 to 1.91)), tocilizumab (0/34, 0%, RR=0.14 (95% CI: 0.0077 to 2.67)), and baricitinib (1/38, 2.6%, RR=0.3 (95% CI: 0.033 to 2.73)) groups.

Interpretation

In hospitalized patients with mild-to-moderate COVID-19, anti-IL-17A or anti-IL-6R therapy were superior or comparable to the JAK1/JAK2 inhibitor, and all three were superior to SOC. Whereas previous studies did not demonstrate significant benefit of anti-IL-17A therapy for severe COVID-19, our data suggest that such therapy could be a rational choice for mild-to-moderate disease, considering the generally high safety profile of IL-17A blockers. The significant increase in blood neutrophil counts in the netakimab group may reflect efflux of neutrophils from inflamed tissues. We therefore hypothesize that neutrophil count and neutrophil-to-lymphocyte ratio could serve as markers of therapeutic efficiency for IL-17A-blocking antibodies in the context of active inflammation.