Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19

Caricchio, Roberto; Abbate, Antonio; Гордеев, И. Г.; Meng, Jamie; Hsue, Priscilla Y.; Neogi, Tuhina; Arduino, Roberto C.; Fomina, Daria; Bogdanov, Roman; Степаненко, Т. А.; Ruíz-Seco, Pilar; González-García, Andrés; Chen, Yu; Li, Yuhan; Whelan, Sarah; Noviello, Stephanie

doi:10.1001/jama.2021.9508

Cited by 153 publications

(82 citation statements)

References 29 publications

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“…Since that initial recommendation, several randomized controlled trials evaluating IL‐1 inhibition in adults with COVID‐19 have been published, with conflicting results. The CAN‐COVID study showed no benefit of canakinumab compared to placebo in adults with COVID‐19 pneumonia and systemic inflammation who were not yet mechanically ventilated (134). The CORIMUNO‐ANA‐1 trial evaluating anakinra for adults with mild‐to‐moderate COVID‐19 and elevated CRP levels was stopped for futility (135).…”

Section: Resultsmentioning

confidence: 99%

American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 3

Henderson

Canna

Friedman

et al. 2022

Arthritis & Rheumatology

182

201

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Objective To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of SARS–CoV‐2 infection. Recommendations are also provided for children with hyperinflammation during COVID‐19, the acute, infectious phase of SARS–CoV‐2 infection. Methods The Task Force is composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS‐C and hyperinflammation in COVID‐19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9‐point scale was used to determine the appropriateness of each statement (median scores of 1–3 for inappropriate, 4–6 for uncertain, and 7–9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting. Results The guidance was approved in June 2020 and updated in November 2020 and October 2021, and consists of 41 final guidance statements accompanied by flow diagrams depicting the diagnostic pathway for MIS‐C and recommendations for initial immunomodulatory treatment of MIS‐C. Conclusion Our understanding of SARS–CoV‐2–related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.

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Section: Resultsmentioning

confidence: 99%

American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 3

Henderson

Canna

Friedman

et al. 2022

Arthritis & Rheumatology

182

201

View full text Add to dashboard Cite

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“…Many trials mainly with IL‐1 or IL‐6 blockade and Janus‐kinase inhibition have been performed to see whether these treatments inhibit the severity of COVID‐19, resulting in positive or negative results with speculation on these results. 41 , 42 , 43 , 44 , 45 On the other hand, recent studies have indicated that treatment with anakinra, an IL‐1 α/β inhibitor, decreased the 28 day mortality only in patients with a plasma level higher than 6 ng/mL of soluble urokinase plasminogen activator receptor (suPAR), an early predictor of severe respiratory failure in COVID‐19 patients, 46 who received dexamethasone. 47 This result suggests that conditions of cytokine production induced by the infection is fairly complex in that the cell interactions involved in cytokine production sequentially change depending on many determinants such as viral dose, functional conditions of involved inflammatory/immune cells, and genetic factors of infected hosts.…”

Section: The Importance Of Sequence and Tempo Of Inflammatory And Imm...mentioning

confidence: 99%

Targeting of neutrophil activation in the early phase of the disease for prevention of Coronavirus disease‐19 severity

Sendo

Yoshitake

Araki

2022

Microbiology and Immunology

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The prevention of the disease severity seems critical for reducing the mortality of Coronavirus (CoV) disease‐19. The neutrophils play a key role in the induction of severity. It is proposed here that inhibition of neutrophil activation and/or cascade reactions of complement, leading to this cell activation at the early phase of the disease, is a potential tool to inhibit aggravation of the disease. The need for appropriate timing in intervention is emphasized as follows. (1) Intervention at the very early stage of severe acute respiratory syndrome‐CoV‐2 infection may harm the defensive host response to the infection because of the critical function of neutrophils in this response, and (2) intervention at too late a stage will not stop the infiltration of fully activated neutrophils that produce large amounts of toxic substances.

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“…However, further revision of available data [64] showed no added benefit to anti-IL-1 agents when compared to standard care that includes dexamethasone or other glucocorticoids [65, 66]. Limited clinical data regarding canakinumab [67] and rilonacept [65, 66] show similar, and disappointing, results. While no RCTs evaluated patients with HM specifically, anecdotal evidence supports the lack of added efficacy of anakinra to standard COVID-19 therapy in patients with HM [68, 69].…”

Section: Resultsmentioning

confidence: 99%

COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response

et al. 2022

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Background: The clinical presentation of coronavirus disease 19 (COVID-19) is the result of intricate interactions between the novel coronavirus and the immune system. In patients with hematologic malignancies (HM), these interactions dramatically change the clinical course and outcomes of COVID-19. Summary: Patients with HM and COVID-19 are at an increased risk for prolonged viral shedding, more protracted and severe presentation, and death, even when compared to other immunocompromised hosts. HM (e.g., multiple myeloma, chronic lymphocytic leukemia) and anticancer treatments (e.g., anti-CD20 agents) that impair humoral immunity markedly increase the risk of severe COVID-19 as well as protracted viral shedding and possibly longer infectivity. Cytokine release syndrome (CRS) is an important player in the pathophysiology of severe and fatal COVID-19. Treatments targeting specific cytokines involved in CRS such as interleukin-6 and Janus kinase have proven beneficial in COVID-19 patients but were not assessed specifically in HM patients. Although neutropenia (as well as neutrophilia) was associated with increased COVID-19 mortality, granulocyte colony-stimulating factors were not beneficial in patients with COVID-19 and may have been associated with worse outcomes. Decreased levels of T lymphocytes and especially decreased CD4+ counts, and depletion of CD8+ lymphocytes, are a hallmark of severe COVID-19, and even more so among patients with HM, underlying the important role of T-helper dysfunction in severe COVID-19. In HM patients with intact cellular immunity, robust T-cell responses may compensate for an impaired humoral immune system. Further prospective studies are needed to evaluate the mechanisms of severe COVID-19 among patients with HM and assess the efficacy of new immunomodulating COVID-19 treatments in this population. Key Messages: Understanding the immunopathology of COVID-19 has greatly benefited from the previous research in patients with HM. So far, no COVID-19 treatments were properly evaluated in patients with HM. Patients with HM should be included in future RCTs assessing treatments for COVID-19.

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Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19

Cited by 153 publications

References 29 publications

American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 3

American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 3

Targeting of neutrophil activation in the early phase of the disease for prevention of Coronavirus disease‐19 severity

COVID-19 in Patients with Hematologic Malignancies: Clinical Manifestations, Persistence, and Immune Response

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