Why has this been in the news?
Researchers have questioned whether repurposing already approved drugs offers any effective treatments of COVID-19. One class of drugs that may improve the body’s immune response to illness is immune modulators (Lancet, May 20, 2020). Coronaviruses may induce the production of cytokines that are present in many auto-inflammatory disorders. Some researchers have suggested that immune modulators might help to neutralize the hyperinflammatory state that is caused by COVID-19 and can be a cause of respiratory distress among patients (Lancet Rheumatology, May 29, 2020).
Monoclonal Antibodies have received media attention as pharmaceutical company Regeneron has applied for Emergency Use Authorization from the US Food and Drug Administration (Johns Hopkins Center for Health Security, October 9, 2020). Researchers are considering the effectiveness of monoclonal antibodies as a treatment for Covid-19 to block or neutralize Coronavirus in affected patients (Biomedicine and Pharmacotherapy, June 4, 2020). The U.S. Food and Drug Administration issued an Emergency Use Authorization for the investigational monoclonal antibody therapy Bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients. Bamlanivimab is authorized for patients who are 12 years of age and older weighing at least 40 kilograms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization (U.S. Food and Drug Administration, November 9, 2020).
How does this apply to my practice?
Bamlanivimab, Sotrovimab, Casirivimab / Imdevimab are the only monoclonal antibody treatments approved for treatment of COVID-19 by Health Canada. They have been approved for treatment of adults and pediatric patients 12 years of age or older with mild to moderate coronavirus disease 2019 (COVID-19), who weigh at least 40 kg and who are at high risk of progressing to severe COVID-19 illness and/or hospitalization. For more information, see the product monographs for these treatments (Health Canada, November 15, 2021). Bamlanivimab is formulated as a solution for infusion (35 mg/mL) and the recommended dose is a single infusion of 700 mg to be administered as soon as possible after a positive test for COVID-19 and to be administered within 10 days following the onset of clinical signs and symptoms of infection. For more information, refer to the Product Monograph for Bamlanivimab (Health Canada, November 20, 2020). Other Immune Modulators are not authorized in Canada for treatment or prophylaxis outside of a randomized controlled trial (Health Canada, December 22, 2020).
The BC Centre for Disease Control (January 29, 2021) recommends Tocilizumab for patients requiring life support due to confirmed COVID-19, including high-flow oxygen support (e.g., Optiflow) if flow rate > 30 L/min and FiO2 > 0.4 OR invasive or non-invasive ventilation OR vasopressor or inotropic support. The REMAP-CAP trial utilized a dosage of 8 mg/kg IV (single dose; up to maximum 800 mg) for this treatment. The BCCDC recommends that Tocilizumab must be administered within 24 hours of the initiation of life support measures. Tocilizumab is not recommended for patients admitted to hospital for more than 14 days with symptoms of COVID-19 or when life support is required for causes other an COVID-19 (BCCDC, January 29, 2021).
Anakinra: Anakinra is currently not recommended for treatment or prophylaxis for COVID-19 as there is insufficient data (NIH, May 12, 2020). Clinical trials are ongoing. Two retrospective trials evaluated the efficacy of Anakinra in Covid-19 patients and found the drug may be effective in reducing mortality, although there are safety concerns related to its use and further research is needed in this area (Drugs, October 17, 2020)
Interferon-α: There is very low-quality evidence that the addition of interferon-α to umifenovir therapy may not affect time to viral clearance or length of hospital stay relative to umifenovir alone (CMAJ, April 29, 2020). There is no evidence available on the harms.
Interferon-β: There is no published evidence regarding benefit or harm of interferon-β in patients with mild to moderate COVID-19 (CMAJ, April 29, 2020). A randomized controlled trial in severe Covid-19 patients indicated that Interferon- β-1b may be effective in shortening the time to clinical improvement without serious adverse events. Further clinical trials with larger sample size are required in this area (International Immunopharmacology, August 24, 2020).
Interferon-λ: There is no published evidence on the benefits and harms in COVID-19. Clinical trials are ongoing.
Intravenous immunoglobulin (IVIG): The BC Centre for Disease Control states that intravenous immunoglobulin G is not recommended for treatment or prophylaxis outside of a randomized controlled trial (October 16, 2020).
Monoclonal antibodies: Bamlanivimab is the only monoclonal antibody treatment approved for treatment of COVID-19 by Health Canada. Approval of Bamlanivimab was based on Health Canada’s analysis of BLAZE-1 Phase 2, randomized, double-blind, placebo-controlled clinical trial studying bamlanivimab for the treatment of subjects with mild to moderate COVID-19. The study identified a potential reduction in the number of Covid-19-related hospitalizations among participants (Health Canada, November 20, 2020). Other Monoclonal Antibodies are not recommended for treatment or prophylaxis outside of a randomized controlled trial (BC Centre for Disease Control, July 6, 2021).
Sarilumab: Not recommended for treatment or prophylaxis outside of a randomized controlled trial (BC Centre for Disease Control,June 13, 2021).
Tocilizumab: In a retrospective observational cohort study, tocilizumab reduced the risk of a composite endpoint of invasive mechanical ventilation or death in adults with severe COVID-19 pneumonia (adjusted hazard ratio 0.61, 95% CI 0.40-0.92; Lancet, June 24, 2020). Another observational study of compassionate use of tocilizumab in patients with COVID-19 pneumonia found that tocilizumab reduced inflammation (measured by C-reactive protein), oxygen requirements, vasopressor support, and mortality. Adverse events and serious adverse events were minimal, but two deaths (7.4%) occurred that were felt unrelated to tocilizumab (Clin Inf Dis, June 23, 2020). A systematic review of retrospective studies indicated Tocilizumab may have potential to treat Covid-19. Due to limitations of this evidence, further large-scale studies are needed in this area (European Journal of Clinical Pharmacology, October 31, 2020).
A systematic review found that, based on low-quality evidence, there is no conclusive evidence that tocilizumab would provide any additional benefit to patients with severe COVID-19 (Int J Antimicrob Agents, July 23, 2020).