Blockade of interleukin seventeen (IL-17A) with secukinumab in hospitalized COVID-19 patients - the BISHOP study
BACKGROUND: Patients with severe COVID-19 seem to evolve with a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction/activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could prevent the deleterious hyperinflammation in COVID-19.
METHODS: BISHOP was a randomized, open-label, single-centre, phase-II controlled trial. Fifty adult patients hospitalized with PCR-positive Covid-19, were randomized 1:1 to receive 300 mg of secukinumab subcutaneously at day-0 plus standard of care (group A) or standard of care alone (group B). A second dose of 300 mg of secukinumab could be administered on day-7, according to staff judgement. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored.
RESULTS: An intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p = .62; There was also no difference in hospitalization time, intensive care unit demand and the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections. There was no difference in the incidence of severe adverse events. Pulmonary thromboembolism occurred only in males and was less frequent in secukinumab-treated patients (4.2% vs. 26.2% p = .04). There was one death in each group. Upper airway viral clearance was also similar in both groups.
CONCLUSION: The efficacy of secukinumab in the treatment of Covid19 was not demonstrated. Secukinumab decreased pulmonary embolism in male patients. There was no difference between groups in adverse events and no unexpected events were observed.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:54 |
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| Enthalten in: |
Infectious diseases (London, England) - 54(2022), 8 vom: 24. Aug., Seite 591-599 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Resende, Gustavo Gomes [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal, Humanized |
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| Anmerkungen: |
Date Completed 24.06.2022 Date Revised 07.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/23744235.2022.2066171 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM340142154 |
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| 100 | 1 | |a Resende, Gustavo Gomes |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Blockade of interleukin seventeen (IL-17A) with secukinumab in hospitalized COVID-19 patients - the BISHOP study |
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| 500 | |a Date Revised 07.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Patients with severe COVID-19 seem to evolve with a compromised antiviral response and hyperinflammation. Neutrophils are critical players in COVID-19. IL-17A plays a major role in protection against extracellular pathogens and neutrophil attraction/activation. We hypothesized that secukinumab, an anti-IL17A monoclonal antibody, could prevent the deleterious hyperinflammation in COVID-19 | ||
| 520 | |a METHODS: BISHOP was a randomized, open-label, single-centre, phase-II controlled trial. Fifty adult patients hospitalized with PCR-positive Covid-19, were randomized 1:1 to receive 300 mg of secukinumab subcutaneously at day-0 plus standard of care (group A) or standard of care alone (group B). A second dose of 300 mg of secukinumab could be administered on day-7, according to staff judgement. The primary endpoint was ventilator-free days at day-28 (VFD-28). Secondary efficacy and safety outcomes were also explored | ||
| 520 | |a RESULTS: An intention-to-treat analysis showed no difference in VFD-28: 23.7 (95%CI 19.6-27.8) in group A vs. 23.8 (19.9-27.6) in group B, p = .62; There was also no difference in hospitalization time, intensive care unit demand and the incidence of circulatory shock, acute kidney injury, fungal or bacterial co-infections. There was no difference in the incidence of severe adverse events. Pulmonary thromboembolism occurred only in males and was less frequent in secukinumab-treated patients (4.2% vs. 26.2% p = .04). There was one death in each group. Upper airway viral clearance was also similar in both groups | ||
| 520 | |a CONCLUSION: The efficacy of secukinumab in the treatment of Covid19 was not demonstrated. Secukinumab decreased pulmonary embolism in male patients. There was no difference between groups in adverse events and no unexpected events were observed | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Covid-19 | |
| 650 | 4 | |a IL-17 | |
| 650 | 4 | |a pulmonary thromboembolism | |
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| 700 | 1 | |a Medeiros, Amanda Fonseca |e verfasserin |4 aut | |
| 700 | 1 | |a Costa E Silva, Alessandra Dias |e verfasserin |4 aut | |
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| 700 | 1 | |a Oliveira, Argenil José de Assis |e verfasserin |4 aut | |
| 700 | 1 | |a Sousa, Denise |e verfasserin |4 aut | |
| 700 | 1 | |a Guimarães, Henrique Cerqueira |e verfasserin |4 aut | |
| 700 | 1 | |a Gomes, Isabella Coelho |e verfasserin |4 aut | |
| 700 | 1 | |a Souza, Renan Pedra |e verfasserin |4 aut | |
| 700 | 1 | |a Aguiar, Renato Santana |e verfasserin |4 aut | |
| 700 | 1 | |a Tunala, Roberto |e verfasserin |4 aut | |
| 700 | 1 | |a Forestiero, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Bueno Filho, Julio Silvio Souza |e verfasserin |4 aut | |
| 700 | 1 | |a Teixeira, Mauro Martins |e verfasserin |4 aut | |
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