Real-world effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab on preventing hospital admission among higher-risk patients with COVID-19 in Wales: a retrospective cohort study

Abstract

Objective To compare the effectiveness of molnupiravir, nirmatrelvir-ritonavir, and sotrovimab with no treatment in preventing hospital admission or death in higher-risk patients infected with SARS-CoV-2 in the community. Design Retrospective cohort study of non-hospitalised adult patients with COVID-19 using the Secure Anonymised Information Linkage (SAIL) Databank. Setting A real-world cohort study was conducted within the SAIL Databank (a secure trusted research environment containing anonymised, individual, population-scale electronic health record (EHR) data) for the population of Wales, UK. Participants Adult patients with COVID-19 in the community, at higher risk of hospitalisation and death, testing positive for SARS-CoV-2 between 16th December 2021 and 22nd April 2022. Interventions Molnupiravir, nirmatrelvir-ritonavir, and sotrovimab given in the community by local health boards and the National Antiviral Service in Wales. Main outcome measures All-cause admission to hospital or death within 28 days of a positive test for SARS-CoV-2. Statistical analysis Cox proportional hazard model with treatment status (treated/untreated) as a time-dependent covariate and adjusted for age, sex, number of comorbidities, Welsh Index of Multiple Deprivation, and vaccination status. Secondary subgroup analyses were by treatment type, number of comorbidities, and before and on or after 20th February 2022, when omicron BA.1 and omicron BA.2 were the dominant subvariants in Wales. Results Between 16th December 2021 and 22nd April 2022, 7,103 higher-risk patients were eligible for inclusion in the study. Of these, 2,040 received treatment with molnupiravir (359, 17.6%), nirmatrelvir-ritonavir (602, 29.5%), or sotrovimab (1,079, 52.9%). Patients in the treatment group were younger (mean age 53 vs 57 years), had fewer comorbidities, and a higher proportion had received four or more doses of the COVID-19 vaccine (36.3% vs 17.6%). Within 28 days of a positive test, 628 (9.0%) patients were admitted to hospital or died (84 treated and 544 untreated). The primary analysis indicated a lower risk of hospitalisation or death at any point within 28 days in treated participants compared to those not receiving treatment. The adjusted hazard rate was 35% (95% CI: 18-49%) lower in treated than untreated participants. There was no indication of the superiority of one treatment over another and no evidence of a reduction in risk of hospitalisation or death within 28 days for patients with no or only one comorbidity. In patients treated with sotrovimab, the event rates before and on or after 20th February 2022 were similar (5.0% vs 4.9%) with no significant difference in the hazard ratios for sotrovimab between the time periods. Conclusions In higher-risk adult patients in the community with COVID-19, those who received treatment with molnupiravir, nirmatrelvir-ritonavir, or sotrovimab were at lower risk of hospitalisation or death than those not receiving treatment.

Nirmatrelvir and risk of hospital admission or death in adults with covid-19: emulation of a randomized target trial using electronic health records

“…Real world effectiveness studies from Israel, Hong Kong, and the UK provided evidence of the effectiveness of nirmatrelvir during the early days of the omicron surge when BA.1 or BA.2 was the predominant subvariant. [3][4][5] Most people infected in the omicron predominant era had been vaccinated (80% of people in the US, 80% in the UK, and 69.1% in the world had received at least one dose of a covid-19 vaccine) and a growing number of people have been reinfected. Our study suggests that the effectiveness of nirmatrelvir is maintained in people who are not vaccinated, in those who are vaccinated, or have received a booster dose, and in those with a primary infection or reinfection.…”

“…Real world evidence studies from Israel, Hong Kong, and the UK suggested that nirmatrelvir was associated with a reduced risk of admission to hospital or death during the early days of the omicron surge. [3][4][5] Omicron has since replaced previous variants, has spawned subvariants, many people recently infected have been vaccinated, and many people have been reinfected (ie, had a previous SARS-CoV-2 infection). [6][7][8] The effectiveness of nirmatrelvir in reducing the risk of admission to hospital or death by vaccination status and by previous history of SARS-CoV-2 infection is not known.…”

Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 and BA.5 subvariant predominance: a systematic literature review

“…Up to February 27, 2023, seven of the 14 studies were published in an international peer-reviewed journal, [26][27][28][29][30][31][32] and seven were published as pre-prints. [33][34][35][36][37][38][39] Three of the preprints have since been published in a peer-reviewed journal . [40][41][42] Studies reported on populations from the US (n=2), UK (n=6), Italy (n=1), Denmark (n=1), France (n=1), Japan (n=2), and Qatar (n=1).…”

“…Seven studies were conducted via secondary analyses of healthcare data, with sources including OpenSAFELY, 38,39 Discover-NOW dataset, 36 SAIL Databank, 33 and the Hospital Episode Statistics database. 35 Other data sources included patient electronic medical records or charts, 27,28,32,37 insurance claims, 26 and laboratory data.…”

“…Four studies compared the effectiveness of sotrovimab relative to untreated control groups or no mAb treatment. 26,31,33,37 Two provided comparative effectiveness data for sotrovimab relative to other treatments (e.g., mAbs, antivirals, corticosteroids). 38,39 Four studies comprised a single-arm treatment design and compared clinical outcomes of sotrovimab-treated patients during BA.2 and/or BA.5 predominant periods versus the BA.1 period.…”