Blockade of interleukin seventeen (IL-17A) with secukinumab in hospitalized COVID-19 patients – the BISHOP study

Abstract

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.

Keywords:

• Covid-19
• secukinumab
• IL-17
• pulmonary thromboembolism
• thromboinflammation

Disclosure statement

GGR received personal payments for lectures from Abbvie, Janssen, Lilly, Novartis and UCB; support for attending meetings and/or travel from Abbvie, Janssen, Lilly, Novartis and UCB; and personal payments for participation on a data safety monitoring board or advisory board Abbvie, Janssen, Lilly and Novartis. RCL received honoraria for presentations and speakers bureaus; and support for attending meetings, including travel and hotel expenses from Novartis. RT and FF were Novartis employees until this submission. ADCS, AFM, ATNS, AJAO, DS, HCG, ICG, MMT, SQL, RSA, JSSBF and RPS declare no competing interests.

Data availability statement

De-identified data can be made available to others on approval of a written reasonable request to the corresponding author.

Additional information

Funding

Novartis Brazil supported this research providing expert input in the development of the project, drug supply, data management, and monitoring. This project was also supported by CNPq (R.S.A.: 312688/2017-2 and 439119/2018-9). MEC/CAPES 118 (14/2020 − 23072.211119/2020-10), FINEP (0494/20 01.20.0026.00), UFMG-NB3, FINEP n° 1139/20 (RSA) and The National Science and Technology Programs (INCT Program project number 465425/2014-3 funded by MCTI/CNPQ/CAPES/FAPS research call 16/2014).