Casirivimab and imdevimab in patients admitted to hospital with COVID-19: RECOVERY Trial

Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor-binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. RECOVERY is a randomized, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. The current study is aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19.

Study Design:

• Eligibility criteria: Patients admitted to the hospital were eligible for the study if they had clinically suspected or laboratory-confirmed SARS-CoV-2 infection and no medical history that might put the patient at significant risk.
• Total 9785 patients enrolled among which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone.
• Primary outcome: 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomization (ie, those who were seronegative) and then in the overall population.
• Secondary outcomes: Time to discharge from hospital, and, in patients not on invasive mechanical ventilation at randomisation, the composite outcome of invasive mechanical ventilation (including ECMO) or death.
• Safety was assessed in all participants who received casirivimab and imdevimab.

Results:

Baseline Characteristics:

• At randomisation, 5272 (54%) were seropositive at baseline, 3153 (32%) were seronegative, and serostatus was unknown for 1360 (14%).
• Other COVID-19 treatments was similar among patients allocated casirivimab and imdevimab and among those allocated usual care, with about 25% receiving remdesivir and about 15% receiving tocilizumab or sarilumab.

Primary Outcome:

• In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab vs. 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69–0·91; p=0·0009). Significant redction by 20%
• If treated with Usual care only, seronegative patients had twice the risk of death of seropositive patients (30% vs 15% mortality)
• Casirivimab and imdevimab significantly reduced mortality in seronegative patients by 20% (absolute benefit: from 30% to 24% mortality).
• The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p =0·002).
• In all randomly assigned patients, there was no significant difference in the primary outcome. 943 (19%)/4839 patients of casirivimab and imdevimab vs. 1029 (21%)/4946 patients of usual care died within 28 days (RR 0·94, 95% CI 0·86–1·02; p=0·14).
• In seronegative patients, discharge alive within 28 days was more common in casirivimab and imdevimab than usual care group patients.

Secondary Outcome:

• The proportional effects of casirivimab and imdevimab on the secondary outcomes of discharge alive from hospital and invasive mechanical ventilation or death differed significantly between seropositive and seronegative patients (p <0·001).
• In seronegative patients not on invasive mechanical ventilation at baseline, casirivimab and imdevimab was associated with a lower risk of progressing to the composite secondary outcome of invasive mechanical ventilation or death.

Safety:

• In the overall study population;

Frequency of fever (in 79 [4%] of 1792 vs 52 [3%] of 1715)

Sudden hypotension (66 [4%] vs 39 [2%]),

• Thrombotic events (31 [2%] vs 24 [1%]) was numerically higher in the casirivimab and imdevimab group vs usual care group,
• While frequency of sudden worsening in respiratory status (369 [21%] vs 372 [22%]) and clinical haemolysis (26 [1%] vs 31 [2%]) was numerically lower casirivimab and imdevimab group vs usual care group.
• Serious adverse reactions reported in seven (<1%) participants were believed to be related to treatment with casirivimab and imdevimab.

Conclusion:

This randomised trial result support the use of combination of casirivimab and imdevimab in seronegative patients admitted to hospital with COVID-19 caused by SARS-CoV-2 variants that are sensitive to these antibodies.

For more details about the prescribing information, click here

Reference: RECOVERY Collaborative Group. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2022 Feb 12;399(10325):665-676. doi: 10.1016/S0140-6736(22)00163-5.

Disclaimer: This article has been published under MD Brand Connect Initiative.

Disclaimer: This content and information provided is intended for update strictlyforRegistered MedicalPractitioners/ Physicians treating Covid 19 only. The information mentioned herein is not intended nor implied to be a substitute for professional medical advice. Any advice regarding the management of any medical condition is totally in the discretion of doctor (Registered Medical Practitioner)/ physician treating Covid 19 patients. Prescription of the drug is the prerogative of doctors (Registered Medical Practitioner/ Physician treating Covid 19) at his /her sole discretion. Physicians treating Covid 19 patients must refer to the fullprescribing information of the product for use of product. Copying, reproduction, circulation of the information published here in any form or by any means either mechanically/ print or electronically without prior consent is strictly prohibited. Any unauthorised person having possession of this document should discard the same or inform/ notify/ return to Cipla Ltd. To report any adverse events/special situation with Cipla medicinal products email at drugsafety@cipla.com. or via the national Pharmacovigilance Programme of India by calling on 1800267 7779 (Cipla number) or you can report to PvPI on 1800 180 3024. By reporting side effects, you can help provide more information on the safetyofthis product. For complete prescribing information, please login www.ciplamed.com.