Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: An observational study
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Abstract
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 a combination of standard-of-care (SOC) and targeted immunosuppressive therapy including anti-IL-17A (netakimab), anti-IL-6R (tocilizumab), or JAK1/JAK2 inhibitor (baricitinib) or with a standard-of-care therapy alone.
Methods
The 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 only: hydroxychloroquine, antiviral, antibacterial, anticoagulant, and dexamethasone (n = 34).
Results
CRP levels significantly decreased after 72 h in the tocilizumab (p = 1 x 10 -5 ) and netakimab (p = 8 x 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 x 10 -5 ) and netakimab (p = 0.01) therapy, and 120 h after the start of tocilizumab (p = 8.6 x 10 -5 ), netakimab (p = 0.001), or baricitinib (p = 4.6 x 10 -4 ) therapy, but not in the SOC group. Blood neutrophil counts (p = 6.4 x 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 of the 34; 8.8%), mortality was lower in netakimab (0 of the 48; 0%, RR = 0.1 (95% CI: 0.0054 to 1.91)), tocilizumab (0 of the 34; 0%, RR = 0.14 (95% CI: 0.0077 to 2.67)), and baricitinib (1 of the 38; 2.6%, RR = 0.3 (95% CI: 0.033 to 2.73)) groups.
Conclusion
In hospitalized patients with mild-to-moderate COVID-19, the combination of SOC with anti-IL-17A or anti-IL-6R therapy were superior or comparable to the combination with JAK1/JAK2 inhibitor, and all three were superior to SOC alone. 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 count 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.
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SciScore for 10.1101/2022.03.31.22269942: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All patients who received tocilizumab, netakimab, or baricitinib provided written informed consent.
IRB: The study was approved by the local ethical committee of the City Clinical Hospital No.52. Procedures: All patients received SOC treatment at the time of hospital admission according to the corresponding COVID-19 Russian guidelines 2020 (Interim guidelines for the prevention, diagnosis and treatment of novel coronavirus infection (COVID-19).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. …
SciScore for 10.1101/2022.03.31.22269942: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: All patients who received tocilizumab, netakimab, or baricitinib provided written informed consent.
IRB: The study was approved by the local ethical committee of the City Clinical Hospital No.52. Procedures: All patients received SOC treatment at the time of hospital admission according to the corresponding COVID-19 Russian guidelines 2020 (Interim guidelines for the prevention, diagnosis and treatment of novel coronavirus infection (COVID-19).Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT03447704 Active, not recruiting International Multicenter Comparative Randomized Placebo-con… NCT03598751 Active, not recruiting Clinical Study of Efficacy and Safety of BCD-085 (Monoclonal… NCT04356937 Completed Efficacy of Tocilizumab on Patients With COVID-19 NCT04320615 Completed A Study to Evaluate the Safety and Efficacy of Tocilizumab i… NCT04381936 Recruiting Randomised Evaluation of COVID-19 Therapy NCT04421027 Completed A Study of Baricitinib (LY3009104) in Participants With COVI… NCT03390101 Active, not recruiting An International Multicenter, Randomized, Double-blind, Plac… NCT05302947 Completed COVID-19 Study at the Russian Clinical and Research Center o… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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