Real-world effectiveness of sotrovimab for the treatment of SARS-CoV-2 infection during Omicron BA.2 subvariant predominance: a systematic literature review
Notice bibliographique
Résumé
Abstract Purpose Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have impacted the in vitro activity of sotrovimab 500 mg, with reduced fold change in EC 50 for the Omicron BA.2 sublineage and onward. The correlation between this reduction and clinical efficacy outcomes is unknown. In the absence of clinical trials assessing the efficacy of sotrovimab against emerging variants, real-world evidence becomes a critical source of information. A systematic literature review (SLR) of published observational studies was undertaken to evaluate the effectiveness of sotrovimab on severe clinical outcomes during the Omicron BA.2 subvariant predominance period. Methods Searches of indexed electronic databases for peer-reviewed journals, preprint articles, and conference abstracts published between January 1, 2022 and November 3, 2022 were undertaken using a combination of search terms for COVID-19, sotrovimab, and observational study design. Study quality was assessed using the Newcastle Ottawa Scale (NOS). Results From the 343 unique titles and abstracts identified, five studies were eligible for inclusion in the SLR. Included studies displayed heterogeneity in study design and population. The OpenSAFELY study, which received a high NOS score and had a sufficient sample of patients treated with sotrovimab during BA.2 predominance, demonstrated clinical effectiveness during both BA.1 (adjusted hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.33–0.88; p = 0.014) and BA.2 (adjusted HR 0.44, 95% CI 0.27–0.71; p = 0.001) periods vs molnupiravir. Furthermore, a US-based study that also received a high NOS score reported that sotrovimab was associated with a lower risk of 30-day all-cause hospitalization or mortality compared with no monoclonal antibody treatment during the BA.2 subvariant surge in March (adjusted relative risk (RR) 0.41, 95% CI 0.27–0.62) and April 2022 (adjusted RR 0.54, 95% CI 0.08–3.54). Although only a limited number of studies evaluated sotrovimab during both the BA.1 and BA.2 periods, these demonstrated that clinical outcomes in patients with COVID-19 treated with sotrovimab were consistently low across both periods. One large study directly compared data from the two periods and found no evidence of a difference in the clinical outcomes of sotrovimab-treated patients with sequencing-confirmed BA.1 and BA.2 (HR 1.17, 95% CI 0.74–1.86). Conclusion The observational data presented in this SLR provide evidence that the effectiveness of sotrovimab (IV 500 mg) is maintained against Omicron BA.2 in both ecological and sequencing-confirmed studies, either through the demonstration of low and comparable rates of severe clinical outcomes between the Omicron BA.1 and BA.2 periods, or by comparison against an active comparator or no treatment within the Omicron BA.2 period. Key points Why carry out this study? Emerging SARS-CoV-2 variants have impacted the in vitro activity of sotrovimab 500 mg, with reduced fold change in EC 50 relative to wild-type for the Omicron BA.2 sublineage and onward; the clinical relevance of this difference on outcomes for BA.2 (and other variants) is unknown. Given the complexity of generating formal clinical trial data in the context of the constantly evolving SARS-CoV-2 landscape, real-world evidence is a key source of information with which to assess the effectiveness of treatments such as sotrovimab on newly predominant or emerging variants. We conducted a systematic literature review to evaluate the effectiveness of sotrovimab for the early treatment of COVID-19 on clinical outcomes during the period predominated by the Omicron BA.2 subvariant. What was learned from the study? Sotrovimab treatment was associated with low proportions of severe clinical outcomes (such as all-cause or COVID-19-related hospitalization or mortality) in patients infected during periods of Omicron BA.2 predominance, despite reduction in the in vitro neutralization activity of sotrovimab. These data support continued clinical effectiveness of sotrovimab during Omicron BA.2 predominance.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».