Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform

Zheng, Bang; Tazare, John; Nab, Linda; Mehrkar, Amir; MacKenna, Brian; Goldacre, Ben; Douglas, Ian; Tomlinson, Laurie A.

doi:10.1101/2023.01.20.23284849

Cited by 21 publications

(70 citation statements)

References 16 publications

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“…The lack of pharmacy data in HES required indirect identification of assumed treatment with sotrovimab. Nonetheless, our results are consistent with those from a recent study, conducted between 16 th December 2021 and 10 th February 2022 using the OpenSAFELY-TPP platform, which reported that 0.96% of patients confirmed to have been treated with sotrovimab had a COVID-19-attributable hospitalisation or death within 28 days of treatment [14]; in our study, 1.0% of patients who were assumed to have been treated with sotrovimab experienced a COVID-19-attributable hospitalisation in the 28-day post-treatment acute period. The results are also similar to those of another recently completed analysis that used data from the Discover database in North-West London, which reported 0.7% of people confirmed to have been treated with sotrovimab experiencing a COVID-19-attributable hospitalisation during the 28 days following treatment (study period was 1 st December 2021 -31 st May 2022 with subvariants predominance as follows: Omicron BA.1 from 1 st December 2021 -28 th February 2022 and Omicron BA.2 from 1 st March 2022 -31 st May 2022) [15].…”

Section: Discussionsupporting

confidence: 92%

“…Similarly, our findings of low rates of COVID-19-attributable deaths and hospitalisations in patients with advanced kidney disease are consistent with a those from a recent study in non-hospitalised patients with COVID-19 on kidney replacement therapy; treatment with sotrovimab resulted in a substantially lower risk of severe COVID-19 outcomes compared with molnupiravir during periods of Omicron BA.1 through to BA.5 subvariant dominance [16]. Finally, our findings are also consistent with the most recent data from the OpenSAFELY-TPP platform, comparing the effectiveness of sotrovimab and Paxlovid in preventing severe COVID-19 outcomes when different subvariants of Omicron were dominant [17]; the risk of severe outcomes was similar between the treatment groups, with no changes observed due to circulation of the BA.5 subvariant.…”

Section: Discussionsupporting

confidence: 89%

“…Recent studies have demonstrated that the Omicron BA.2 variant is similar in severity to the Omicron BA.1 variant [13, 14, 18, 19], although it may have increased severity in certain populations such as the elderly [20]. Our large population-based study across England contributes to the overall favorable weight of evidence to support clinical benefit of sotrovimab as an early treatment for COVID-19 through Omicron sub-variant predominance periods, especially for patients at higher risk of developing severe symptoms such as those with severe renal diseases and active cancer.…”

Section: Discussionmentioning

confidence: 99%

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Characteristics and Outcomes of COVID-19 Patients Presumed to be Treated with Sotrovimab in NHS Hospitals in England

Levick

Boult

Gibbons

et al. 2023

Preprint

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Introduction:There is limited real-world evidence describing the effectiveness of early treatments for Coronavirus disease 2019 (COVID-19) during the period where Omicron was the dominant variant. Here we describe characteristics and acute clinical outcomes in patients with COVID-19 treated with a monoclonal antibody (mAb; presumed to be sotrovimab) across six distinct periods covering the emergence and subsequent dominance of Omicron subvariants (BA.1, BA.2 and BA.5) in England.Methods:Retrospective cohort study using data from Hospital Episode Statistics database between 1stJanuary – 31stJuly 2022. Included patients were aged ≥12 years and received a mAb delivered by a National Health Service (NHS) hospital as a day-case, for which the primary diagnosis was COVID-19. Patients were presumed to have received sotrovimab on the basis of available NHS data showing that 99.98% of individuals who received COVID-19 treatment during the period covered by the study were actually treated with sotrovimab. COVID-19-attributable hospitalisations were reported overall and across six distinct periods of Omicron sub-variant prevalence. A multivariate Poisson regression model was used to estimate incidence rate ratios for each period. Subgroup analyses were conducted in patients with severe renal disease and active cancer.Results:In total, 10,096 patients were included. The most common high-risk comorbidities were Immune-Mediated Inflammatory Disorders (43.0%; n = 4,337), severe renal disease (14.1%; n = 1,422), rare neurological conditions (10.4%; n = 1,053) and active cancer (9.0%; n = 910). The proportions of patients with a COVID-19-attributable hospitalisation was 1.0% (n = 96), or with a hospital visit due to any cause was 4.6% (n = 465) during the acute period. The percentage of patients who died due to any cause during the acute study period was 0.3% (n = 27). COVID-19-attributable hospitalisation rates were consistent among subgroups and no significant differences (p-values ranged from 0.13 to 0.64) were observed across periods of Omicron subvariants.Conclusion:Low levels of COVID-19-attributable hospitalisations and deaths were recorded in mAb-treated patients. Results were consistent for patients with severe renal disease and active cancer. No evidence of differences in hospitalisation rates were observed whilst Omicron BA.1, and BA.2 or BA.5 subvariants were predominant, despite reported reductions in in vitro neutralisation activity of sotrovimab against BA.2 and BA.5.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Characteristics and Outcomes of COVID-19 Patients Presumed to be Treated with Sotrovimab in NHS Hospitals in England

Levick

Boult

Gibbons

et al. 2023

Preprint

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“…Figure 1 shows the flow diagram of study selection according to its title, abstract, and full text. After removing duplicated records, seventeen studies, 19 , 20 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 (two RCTs and fifteen observational studies) with 27,429 patients were included in the meta‐analysis. The main characteristics of included studies are listed in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

“…Data are available online for the included studies. 19 , 20 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 …”

Section: Data Availability Statementmentioning

confidence: 99%

Efficacy and safety of sotrovimab in patients with COVID‐19: A rapid review and meta‐analysis

Amani

2022

Reviews in Medical Virology

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The therapeutic potential of sotrovimab in the treatment of coronavirus disease 2019 (COVID‐19) is a controversial issue. The aim of this study was to evaluate the efficacy and safety of sotrovimab in COVID‐19 patients. To this end, PubMed, Cochrane Library, Embase, Web of Science, medRxiv, and Google Scholar were searched up to 15 August 2022. The reference lists of key studies were also scanned to find additional records. Meta‐analysis was performed using Comprehensive Meta‐Analysis. Seventeen studies involving 27,429 patients were included. A significant difference was observed in mortality rate (odds ratio [OR] = 0.40; 95% CI: 0.25–0.63, p = 0.00), hospitalisation rate (OR = 0.53; 95% CI: 0.43–0.65. p = 0.00), hospital or death rate (OR = 0.43; 95% CI: 0.25–0.73, p = 0.00), the need for mechanical ventilation (OR = 0.57; 95% CI: 0.33–0.96, p = 0.03), and ICU admission (OR = 0.33; 95% CI: 0.17–0.67, p = 0.00) of the sotrovimab‐receiving group compared to those having no sotrovimab. However, no significant difference was observed between the two groups in terms of disease progression (OR = 0.45; 95% CI: 0.16–1.24, p = 0.12) and emergency department visit (OR = 1.01; 95% CI: 0.83–1.24, p = 0.87). The two groups had no significant difference in terms of incidence of adverse events (OR = 0.98; 95% CI: 0.78–1.23, p = 0.88). The findings of the present meta‐analysis support that sotrovimab could be an effective and safe treatment option to reduce mortality and hospitalisation rate in both Delta and Omicron Variants of COVID‐19.

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Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID‐19: A systematic review and meta‐analysis

Amani

Akbarzadeh

Amani

et al. 2023

Journal of Medical Virology

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This study aimed to compare the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) with molnupiravir in the treatment of coronavirus disease 2019 . To end this, PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar were systematically searched to collect relevant evidence up to February 15, 2023. The risk of bias was evaluated using the risk of bias in nonrandomized studies of interventions tool. Data were analyzed using Comprehensive Meta-Analysis software. Eighteen studies involving 57 659 patients were included in the meta-analysis. The meta-analysis showed a significant difference between nirmatrelvir/ritonavir and molnupiravir in terms of all-cause mortality rate (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.44-0.67), all-cause hospitalization rate (OR = 0.61, 95% CI: 0.54-0.69), death or hospitalization rate (OR = 0.61, 95% CI: 0.38-0.99), and negative polymerase chain reaction conversion time (mean difference = −1.55, 95% CI: −1.74 to −1.37). However, no significant difference was observed between the two groups in terms of COVID-19 rebound (OR = 0.87, 95% CI: 0.71-1.07). In terms of safety, although the incidence of any adverse events was higher in the nirmatrelvir/ritonavir group (OR = 2.52, 95% CI:1.57-4.06), no significant difference was observed between the two treatments in terms of adverse events leading to treatment discontinuation (OR = 1.18, 95% CI: 0.69-2.00). The present meta-analysis demonstrated the significant superiority of nirmatrelvir/ritonavir over molnupiravir in improving clinical efficacy in COVID-19 patients during the prevalence of Omicron variant. These findings, however, need to be further confirmed.

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Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in non-hospitalised patients: observational cohort study using the OpenSAFELY platform

Cited by 21 publications

References 16 publications

Characteristics and Outcomes of COVID-19 Patients Presumed to be Treated with Sotrovimab in NHS Hospitals in England

Characteristics and Outcomes of COVID-19 Patients Presumed to be Treated with Sotrovimab in NHS Hospitals in England

Efficacy and safety of sotrovimab in patients with COVID‐19: A rapid review and meta‐analysis

Comparative efficacy and safety of nirmatrelvir/ritonavir and molnupiravir for COVID‐19: A systematic review and meta‐analysis

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