This article is part of a series: Guest blogs

In a recent OpenSAFELY blog we described some of our research findings on the coverage of COVID-19 treatments and the comparative effectiveness between them using the OpenSAFELY platform. In this guest blog, Bang Zheng and Laurie Tomlinson from the London School of Hygiene and Tropical Medicine are delighted to present some of their new pieces of evidence on the comparative effectiveness and safety of currently recommended COVID-19 therapeutics in the community settings.

Comparative effectiveness of Paxlovid versus sotrovimab and molnupiravir:

Paxlovid (nirmatrelvir/ritonavir), an oral antiviral against COVID-19, is strongly recommended as the first-line treatment for high-risk non-hospitalised patients in guidelines from World Health Organization (WHO) as well as the UK National Institute for Health and Care Excellence (NICE). However, the clinical trial supporting the routine clinical use of Paxlovid was conducted in an unvaccinated population before the Omicron wave, and had limited inclusion of certain vulnerable subgroups such as immunosuppressed individuals. In addition, there have been no clinical trials directly comparing the efficacy between Paxlovid and other alternative COVID-19 therapeutics.

In our study published in The Lancet Regional Health – Europe, we have analysed the clinical data of high-risk COVID-19 patients who have received the outpatient treatment during the Omicron waves. Our analysis with granular real-world data in the OpenSAFELY-TPP database showed similar effectiveness in preventing severe COVID-19 outcomes between Paxlovid and sotrovimab, a neutralising monoclonal antibody against COVID-19. In contrast, Paxlovid appeared to be more effective than molnupiravir, which is another oral antiviral against COVID-19. Such timely real-world evidence on the comparative effectiveness between COVID-19 treatments is important for policy making and clinical care, especially in clinical settings where the decision is over which treatment to use rather than whether to treat or not.

Comparative effectiveness study in patients with kidney replacement therapy:

Paxlovid, though recommended as the first-line treatment, is contraindicated for patients with severe renal impairment or those receiving immunosuppressive drugs for kidney transplantation, who have been consistently at high risk of severe outcomes from COVID-19. Therefore, clinical evidence on the available treatment options for these patients in the UK, namely sotrovimab and molnupiravir, is urgently needed.

In our study published in Clinical Kidney Journal, we have focused on the therapeutics data of COVID-19 patients who were on kidney replacement therapy. Using the securely linked electronic health record data between OpenSAFELY-TPP and the UK Renal Registry, we found that among this population across England, treatment with sotrovimab was associated with substantially lower risk of COVID-19 related hospitalisation/death than molnupiravir. In addition, we have established a research collaboration with the Scottish Renal Registry, and consistent evidence was obtained based on data from patients in Scotland.

This study has been cited in the NICE guideline, which recommends sotrovimab as the treatment option for patients contraindicated to Paxlovid. This work demonstrates the role that OpenSAFELY can play in informing areas of uncertainty in clinical guidelines.

Anaphylaxis risk following COVID-19 treatment for non-hospitalised patients:

Following the change of delivery method for outpatient COVID-19 therapeutics across England in June 2023, the way treatments are delivered has been reorganised by local Integrated care boards (ICB). In this context, data on adverse events like anaphylaxis is important for the safe administration of these treatments in community settings and health service planning, especially for sotrovimab which requires intravenous infusion. We conducted a descriptive analysis on the anaphylaxis events following outpatient COVID-19 treatment, indicating that anaphylaxis risks were similar between sotrovimab and Paxlovid users, which were slightly higher than untreated patients. This work has been published in Wellcome Open Research. A formal and systematic investigation on the safety of COVID-19 therapeutics based on OpenSAFELT platform is being conducted in collaboration with colleagues in KCL.

Future Research and Uncertainty of Data Availability:

Despite this hugely impactful work we are currently unsure if we can continue our work on evaluating the effectiveness of COVID-19 therapeutics. As discussed in our previous blog, in June 2023 there was a significant change to how COVID-19 therapeutics were supplied to patients. This has meant that how services are delivered vary across different localities, resulting in changes in the collected data. Consequently this has posed a challenge in tracking the recipients of COVID-19 therapeutics within OpenSAFELY. While we are closely monitoring the situation, there are two key factors that would help us deliver more of the impactful work described above. First, an increase in GPs prescribing these medicines. If GPs take over responsibility for prescribing these medicines we will be able to see them in OpenSAFELY. Second, the creation of a regularly updated ‘high-cost drug’ dataset for broad accessibility, including through the OpenSAFELY-TPP platform. See our paper on a comprehensive high cost drugs dataset from the NHS in England for further details.

Get in touch:

Using the OpenSAFELY platform has allowed us to generate timely clinical evidence on COVID-19 therapeutics in multiple aspects, and the close collaboration between LSHTM, the Bennett Institute for Applied Data Science at the University of Oxford and TPP improved the efficiency and quality of project management and implementation. All of the code for our projects can be found in the corresponding OpenSAFELY repositories here and here. For more information on our experience with using OpenSAFELY or our OpenSAFELY projects, please contact me at .