Sarilumab for hospitalized patients with COVID-19
References
1. Afra K, Chen LYC, Sweet D. Tocilizumab for hospitalized patients with COVID-19. CMAJ 2021 Apr 12;193(15):E521.
2. Pai M, Morris A, Murthy S. Opinion: Canadians should ask why we are running out of drugs to treat COVID-19. The Globe and Mail 2021 April 25.
3. Product monograph: KEVZARA® sarilumab. Sanofi-aventis Canada Inc., Laval (QC). 2017 Jan. 12, revised 2019 Aug. 8. Available from: https://pdf.hres.ca/dpd_pm/00052589.PDF.
4. REMAP-CAP Investigators; Gordon AC, Mouncey PR, Al-Beidh F, et al. Interleukin-6 receptor antagonists in critically ill patients with COVID-19. N Engl J Med 2021 Apr 22;384(16):1491-1502.
5. Lescure FX, Honda H, Fowler RA, et al. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2021 Mar 4:S2213-2600(21)00099-0.
Afra and colleagues provide a timely review of a crucial treatment for hospitalized patients with COVID-19.(1) Unfortunately, ongoing tocilizumab shortages with uncertain future supply threatens our ability to optimally care for patients.(2)
Akin to tocilizumab, another repurposed interleukin-6 (IL-6) receptor inhibitor is sarilumab, a fully human monoclonal antibody that is currently approved in Canada for moderate-severe rheumatoid arthritis.(3)
In the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community-Acquired Pneumonia study, both tocilizumab (n=353) and sarilumab (n=48) treated patients had improved outcomes, including survival.(4) Median organ support-free days with sarilumab was 11 (10 with tocilizumab). Mortality with sarilumab was 22%, versus 36% in the standard of care group - a number needed to treat of approximately 7, acknowledging the small sample size.(4) These outcomes are somewhat tempered by the results of a placebo-controlled randomized trial of sarilumab 200mg (n=159) and 400mg (n=178),(5) which demonstrated a non-statistically significant trend towards improved survival. This study acknowledges they may not have recruited sufficiently critically ill patients, with only approximately 60% of patients receiving at least one dose of systemic corticosteroids.(5)
The main practical limitations of sarilumab include uncertain supply and logistical preparation/administration barriers. While sarilumab is formulated as a pre-filled syringe for subcutaneous injection, most COVID-19 studies administered sarilumab as an intravenous infusion.(4,5) Clinicians will need to appropriately prepare, administer and monitor treatment.
Sarilumab should be considered as an alternative to tocilizumab to extend supply of IL-6 receptor inhibitor therapy while, hopefully, efforts to procure adequate tocilizumab supply are made.