دورية أكاديمية
Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: An observational study.
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. |
References: | Dermatol Ther (Heidelb). 2021 Aug;11(4):1319-1332. (PMID: 34060012) Ther Clin Risk Manag. 2008 Aug;4(4):767-75. (PMID: 19209259) Front Immunol. 2018 Jun 28;9:1510. (PMID: 30002661) Int Immunopharmacol. 2020 Sep;86:106749. (PMID: 32645632) Leukemia. 2021 Oct;35(10):2917-2923. (PMID: 34385593) Cytokine. 2018 Apr;104:8-13. (PMID: 29414327) Crit Care Med. 2016 Mar;44(3):496-502. (PMID: 26540401) Hum Vaccin Immunother. 2017 Sep 2;13(9):1972-1988. (PMID: 28841363) Clin Med (Lond). 2019 May;19(3):260. (PMID: 31092526) Scand J Trauma Resusc Emerg Med. 2020 Jul 13;28(1):66. (PMID: 32660623) Expert Opin Drug Saf. 2021 Sep;20(9):1125-1136. (PMID: 34162299) Cytokine. 2021 Jan;137:155323. (PMID: 33045526) Am J Respir Crit Care Med. 2020 Sep 15;202(6):812-821. (PMID: 32584597) N Engl J Med. 2021 Feb 25;384(8):693-704. (PMID: 32678530) Biosci Rep. 2019 Feb 8;39(2):. (PMID: 30655311) Lancet Respir Med. 2020 Apr;8(4):420-422. (PMID: 32085846) Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620933508. (PMID: 32539627) Nat Commun. 2020 Jul 6;11(1):3434. (PMID: 32632085) Pharmacotherapy. 2020 Aug;40(8):843-856. (PMID: 32542785) Front Immunol. 2021 Feb 18;12:613422. (PMID: 33679753) Eur Cytokine Netw. 2021 Mar 1;32(1):8-14. (PMID: 34346869) Nat Rev Immunol. 2010 Jul;10(7):479-89. (PMID: 20559326) J Clin Pharmacol. 2014 Dec;54(12):1354-61. (PMID: 24965573) Rheumatol Ther. 2018 Jun;5(1):21-42. (PMID: 29502236) Lancet Respir Med. 2021 Dec;9(12):1407-1418. (PMID: 34480861) Trials. 2021 Jan 11;22(1):43. (PMID: 33430891) Lancet Reg Health Am. 2021 Oct;2:100062. (PMID: 34485970) Mucosal Immunol. 2016 May;9(3):610-20. (PMID: 26376362) Eur J Immunol. 2013 Jun;43(6):1529-44. (PMID: 23505056) Drugs. 2020 Dec;80(18):1929-1946. (PMID: 33068263) Lancet Rheumatol. 2020 Aug;2(8):e474-e484. (PMID: 32835257) Immunity. 2008 Oct 17;29(4):628-36. (PMID: 18848474) J Immunol. 2015 Jul 1;195(1):87-95. (PMID: 26002979) Cytokine. 2021 Oct;146:155627. (PMID: 34237556) Oncotarget. 2017 Oct 4;8(55):93704-93711. (PMID: 29212183) Nat Rev Rheumatol. 2020 Aug;16(8):465-470. (PMID: 32561873) N Engl J Med. 2020 Dec 10;383(24):2333-2344. (PMID: 33085857) J Microbiol Immunol Infect. 2020 Jun;53(3):368-370. (PMID: 32205092) Ther Clin Risk Manag. 2020 Aug 04;16:705-714. (PMID: 32801727) J Allergy Clin Immunol. 2020 Jul;146(1):128-136.e4. (PMID: 32425269) Sci Adv. 2021 Jan 1;7(1):. (PMID: 33187978) Cells. 2021 Jun 19;10(6):. (PMID: 34205262) Br J Clin Pharmacol. 2021 Mar;87(3):1533-1540. (PMID: 32639062) Proc Natl Acad Sci U S A. 2020 May 19;117(20):10970-10975. (PMID: 32350134) Lancet. 2020 Feb 15;395(10223):497-506. (PMID: 31986264) Signal Transduct Target Ther. 2021 Jul 7;6(1):255. (PMID: 34234112) Int Immunopharmacol. 2020 Dec;89(Pt A):107018. (PMID: 33045577) J Immunol. 2017 Apr 1;198(7):2805-2818. (PMID: 28219889) Arthritis Res Ther. 2020 May 12;22(1):111. (PMID: 32398096) JAMA Intern Med. 2021 Jan 1;181(1):32-40. (PMID: 33080017) Resuscitation. 2021 Feb;159:150-157. (PMID: 33176170) Lancet Respir Med. 2020 Dec;8(12):1233-1244. (PMID: 33075298) J Rheumatol. 2018 Jan;45(1):14-21. (PMID: 28811354) Lancet. 2020 Mar 28;395(10229):1033-1034. (PMID: 32192578) Infect Dis (Lond). 2022 Aug;54(8):591-599. (PMID: 35485381) Expert Rev Anti Infect Ther. 2022 May;20(5):773-779. (PMID: 34743661) N Engl J Med. 2021 Apr 22;384(16):1503-1516. (PMID: 33631066) J Med Virol. 2021 Mar;93(3):1459-1464. (PMID: 32790075) J Investig Med. 2022 Jan;70(1):55-60. (PMID: 34561232) |
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 |
تدمد: | 1932-6203 |
---|---|
DOI: | 10.1371/journal.pone.0273340 |