In a recent study posted to the medRxiv* preprint server, researchers compared the efficacy of sotrovimab [an intravenously administered neutralizing monoclonal antibody (nMAb)] and molnupiravir (an orally administered antiviral drug) in preventing severe coronavirus disease 2019 (COVID-19) outcomes among non-hospitalized and high-risk COVID-19 patients across England.
Two phase 3 randomized controlled trials (RCTs) conducted among unvaccinated non-hospitalized COVID-19 patients who were at high risk of progression to severe COVID-19 or death showed that sotrovimab treatment was highly effective in preventing hospitalization or death, whereas molnupiravir was moderately effective (relative risk reductions 79% versus 30%).
However, studies that comparatively evaluate the efficacy of the two medications in routine care settings are limited. It is yet not clear whether their efficacy persists among vaccinated individuals, patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infections, and patients with renal or hepatic impairments. Further, it is uncertain if molnupiravir treatment is effective among non-White patients with prior SARS-CoV-2 infections and diabetes.
About the study
In the present national observational cohort study, researchers compared the efficacy of sotrovimab and molnupiravir in preventing COVID-19 progression among non-hospitalized high-risk SARS-CoV-2-positive patients across England. They also explored the potential modifying effects of different clinical and demographic clinical factors on the effectiveness of the two medications.
The study cohort comprised non-hospitalized lateral flow test- or polymerase chain reaction (PCR)-confirmed SARS-CoV-2-positive adults highly prone to severe COVID-19 outcomes and treated with molnupiravir or sotrovimab between 16 December 2021 and 10 February 2022. COVID-19 medicine delivery units (CMDUs) administered the drugs in community settings. Patients were excluded if they were previously treated with any other antivirals or nMAbs for COVID-19 (n=21).
The high-risk participants were identified as those belonging to any of the following categories: Down syndrome patients, solid organ cancer patients, patients with hematological disorders, renal disorders, hepatic disorders, immune system-associated inflammatory diseases, primary immunodeficiencies, HIV/AIDS (human immunodeficiency virus/ acquired immunodeficiency syndrome), solid organ or stem cell transplant recipients or rare neurological disorders.
Data were obtained from near real-time electronic health records (EHR) of patients of a general practice (GP) which uses the test productivity pack (TPP) software. The EHR data were linked securely with the OpenSAFELY-TPP platform data on SARS-CoV-2 infection and its therapeutics, hospitalizations, and deaths.
The primary outcome was COVID-19-associated hospitalizations or deaths within 28 days of initiating treatment. Secondary outcomes were 28-day all-cause hospitalization or death and 60-day COVID-19-associated hospitalization/death. Cox proportional hazards models and hazard ratio (HR) were used for the analysis.
Out of 5,951 participants, 2,633 and 3,288 participants were treated with molnupiravir and sotrovimab, respectively. The average age of the participants was 52 years, and most of them (59%) were women, 89% were White, and 87.4% had received ≥3 SARS-CoV-2 vaccine doses.
Within a 28-day-period of initiating treatment, 84 COVID-19-associated hospitalizations/deaths were noted among participants treated either with sotrovimab (n=31) or molnupiravir (n=53). Of the 84 patients, 25 (0.4%) COVID-19-associated deaths were observed during the 28-day-follow-up-period (7 and 18 patients were treated with sotrovimab and molnupiravir, respectively). Of the patients who died, 16 and 9 patients were hospitalized and non-hospitalized, respectively.
Cox regression modeling showed that the high-risk categories, calendar week, vaccination status, body mass index (BMI), presence of comorbidities, and sotrovimab treatment were associated with significantly lesser 28-day COVID-19 related hospitalization/death than molnupiravir treatment (HR=0.5). The findings were consistent after propensity score weighted Cox modeling (HR=0.5) and when limiting the analysis to participants who received all COVID-19 vaccine doses. (HR=0.5).
Among the secondary outcomes, 92 cases (1.5%) of COVID-19-associated hospitalizations/deaths were observed during the 60-day-follow-up after initiating treatment (32 and 60 cases among participants treated with sotrovimab and molnupiravir, respectively). Cox regression modeling showed a substantially lower risk among sotrovimab-treated participants than molnupiravir-treated participants (HRs ranged between 0.4 and 0.5).
Overall, the study findings showed that the risk of severe COVID-19 outcomes (hospitalizations and deaths) was substantially lower with sotrovimab treatment than with molnupiravir treatment among non-hospitalized high-risk COVID-19 patients treated in routine care settings across England. The findings support the United Kingdom (UK) current clinical guidelines that prioritize sotrovimab over molnupiravir for preventing COVID-19 progression among non-hospitalized SARS-CoV-2-positive patients.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.