Anti-IL-17 monoclonal antibodies in hospitalized patients with severe COVID-19: A pilot study

Авдеев, С. Н.; Trushenko, Natalia V.; Tsareva, Natalia A.; Yaroshetskiy, Andrey I.; Merzhoeva, Zamira M.; Нуралиева, Г. С.; Nekludova, Galina; Чикина, С. Ю.; Gneusheva, T. Yu.; Suvorova, O. N.; Shmidt, Anna E.

doi:10.1016/j.cyto.2021.155627

Cited by 42 publications

(39 citation statements)

References 13 publications

(15 reference statements)

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“…These wide favorable actions support a protective role of IL-17 inhibitors in COVID-19 [ 32 ]. Very recently, in a pilot case-control study, it was demonstrated that the patients with severe COVID-19 treated with anti-IL-17 monoclonal antibodies showed moderated inflammatory response and improved oxygenation; however, treatment did not seem to improve survival, or reduce mechanical ventilation requirement [ 33 ]. With the aim of achieving new target-specific drug therapies, examining cytokines known to be associated with chronic hyper-inflammatory diseases could potentially lead us in repurposing drugs and improving the existing therapeutic strategies.…”

Section: Discussionmentioning

confidence: 99%

Evaluating the Role of the Interleukin-23/17 Axis in Critically Ill COVID-19 Patients

Jahaj

Vassiliou

Keskinidou

et al. 2021

JPM

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Studies have hypothesized a potential role of the interleukin (IL)-23/17 axis in coronavirus disease 2019 (COVID-19). However, to date, levels of IL-23 and 17 have not been compared between critically ill COVID-19 patients and critically ill non-COVID-19 patients. IL-23 and 17 were measured on admission to the intensive care unit (ICU) in critically ill COVID-19 (N = 38) and critically ill non-COVID-19 (N = 34) patients with an equal critical illness severity. Critically ill non-COVID-19 patients did not have sepsis or septic shock on ICU admission. None of the enrolled patients had previously received corticosteroids. In our study, circulating IL-17 levels were higher in the COVID-19 patients. More specifically, critically ill COVID-19 patients had levels of 0.78 (0.05–1.8) pg/mL compared to 0.11 (0.05–0.9) pg/mL in the critically ill non-COVID-19 patients (p = 0.04). In contrast, IL-23 levels were comparable between groups. A group of patients hospitalized in the specialized COVID-19 clinic (N = 16) was also used to evaluate IL-17 and IL-23 levels with respect to COVID-19 severity. Non-critically ill COVID-19 patients had undetectable levels of both cytokines. Our results support the notion of inhibiting IL-17 in critical COVID-19 infection.

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Section: Discussionmentioning

confidence: 99%

Evaluating the Role of the Interleukin-23/17 Axis in Critically Ill COVID-19 Patients

Jahaj

Vassiliou

Keskinidou

et al. 2021

JPM

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“…All treatment-related adverse events were typical for IL-17 inhibitors: neutropenia, lymphopenia, and upper respiratory tract infections. The potential efficacy of netakimab for treating cytokine release syndrome in COVID-19 has been examined in at least two retrospective studies: in comparison with patients who did not receive anti-cytokine therapy or were treated by tocilizumab 57 , and in comparison with SOC therapy including hydroxychloroquine, azithromycin, low-molecular-weight heparins, and corticosteroids 58 . Both studies indicated that netakimab is safe.…”

Section: Discussionmentioning

confidence: 99%

Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: a retrospective cohort study

Bryushkova

Skatova

Mutovina

et al. 2022

Preprint

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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 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 (3/34, 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.

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“…IL-17 inhibitors did not increase the risk of progressive COVID-19 [108]. For the use of IL-17 antagonists in COVID-19, there are very scarce data, limited to a recent study from Russia, which fail to show clinical benefit of netakimab [109].…”

Section: Anti-il-17 Antagonistsmentioning

confidence: 98%

Immune dysfunction in COVID-19 and judicious use of antirheumatic drugs for the treatment of hyperinflammation

Tufan¹,

Matucci‐Cerinic²

2021

Turk J Med Sci

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In the Wuhan province of China, almost two years ago, in December 2019, the novel Coronavirus 2019 has caused a severe involvement of the lower respiratory tract leading to an acute life-threatening respiratory syndrome, coronavirus disease-19 (COVID-19). Subsequently, coronavirus 2 (SARS-CoV-2) rapidly spread to the entire world causing a pandemic and affected every single person on earth either directly or indirectly with destroying all facets of social life and economy. Since the announcement of COVID-19 as a global pandemic, we have witnessed tremendous scientific work on all aspects of COVID-19 across the globe, which has never been witnessed before. The most remarkable achievement would be the introduction of vaccines, which provide protection from the severe infection and is the only premise for the control of disease. However, despite the tremendous work, the number of treatments either antiviral or immunomodulatory for infected patients are considerably limited, yet disease is causing substantial morbidity and mortality. COVID-19 follows heterogenous disease course among infected individuals, and dysregulated immune system is primarily responsible for the worse outcomes. Immune deficiency, being on corticosteroids for inflammatory diseases, delayed interferon response and advanced age adversely influence prognosis with impairing viral clearance. On the other hand, exuberant immune response with features of cytokine storm is the leading cause of death, which can be alleviated by use of either general immunosuppression with corticosteroids or selective neutralization of potent pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6. Herein, we summarized the potential effective immunomodulatory treatments emphasizing in which patient population it is the most suitable, which dose should be administered, and which is the most appropriate timepoint to administer the drug during the course of the disease.

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Anti-IL-17 monoclonal antibodies in hospitalized patients with severe COVID-19: A pilot study

Cited by 42 publications

References 13 publications

Evaluating the Role of the Interleukin-23/17 Axis in Critically Ill COVID-19 Patients

Evaluating the Role of the Interleukin-23/17 Axis in Critically Ill COVID-19 Patients

Tocilizumab, netakimab, and baricitinib in patients with mild-to-moderate COVID-19: a retrospective cohort study

Immune dysfunction in COVID-19 and judicious use of antirheumatic drugs for the treatment of hyperinflammation

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