دورية أكاديمية
أعرض في EDS

Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: An observational study.

التفاصيل البيبلوغرافية
العنوان: Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: An observational study.
المؤلفون: Bryushkova EA; Pirogov Russian National Research Medical University, Moscow, Russia.; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.; Lomonosov Moscow State University, Moscow, Russia., Skatova VD; Pirogov Russian National Research Medical University, Moscow, Russia.; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia., Mutovina ZY; City Clinical Hospital No.52 of Moscow Healthcare Department, Moscow, Russia., Zagrebneva AI; City Clinical Hospital No.52 of Moscow Healthcare Department, Moscow, Russia., Fomina DS; City Clinical Hospital No.52 of Moscow Healthcare Department, Moscow, Russia.; I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow, Russian Federation., Kruglova TS; City Clinical Hospital No.52 of Moscow Healthcare Department, Moscow, Russia., Akopyan AA; Pirogov Russian National Research Medical University, Moscow, Russia., Strazhesko ID; Pirogov Russian National Research Medical University, Moscow, Russia., Lukyanov SA; Pirogov Russian National Research Medical University, Moscow, Russia., Tkacheva ON; Pirogov Russian National Research Medical University, Moscow, Russia., Lysenko MA; Pirogov Russian National Research Medical University, Moscow, Russia.; City Clinical Hospital No.52 of Moscow Healthcare Department, Moscow, Russia., Chudakov DM; Pirogov Russian National Research Medical University, Moscow, Russia.; Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.
المصدر: PloS one [PLoS One] 2022 Aug 24; Vol. 17 (8), pp. e0273340. Date of Electronic Publication: 2022 Aug 24 (Print Publication: 2022).
نوع المنشور: Journal Article; Observational Study; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: COVID-19 Drug Treatment*, Adult ; Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Azetidines ; Humans ; Purines ; Pyrazoles ; SARS-CoV-2 ; Sulfonamides ; Treatment Outcome
مستخلص: Objective: 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.
Competing Interests: The authors have declared that no competing interests exist.
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المشرفين على المادة: 0 (Anti-Inflammatory Agents)
0 (Antibodies, Monoclonal)
0 (Antibodies, Monoclonal, Humanized)
0 (Azetidines)
0 (Purines)
0 (Pyrazoles)
0 (Sulfonamides)
D3IAG45DAK (netakimab)
I031V2H011 (tocilizumab)
ISP4442I3Y (baricitinib)
تواريخ الأحداث: Date Created: 20220824 Date Completed: 20220826 Latest Revision: 20221207
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9401152
DOI: 10.1371/journal.pone.0273340
PMID: 36001576
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0273340