The safety of antivirals and neutralising monoclonal antibodies used in prehospital treatment of Covid-19

This proof-of-principle pharmacovigilance study used Electronic Health Record (EHR) data to examine the safety of sotrovimab, paxlovid and molnupiravir in prehospital treatment of Covid-19 In this guest blog, Katie Bechman describes the research that she has undertaken with the help of her team from King’s College London using OpenSAFELY.

Summary

Our research team at King’s College London have been using the OpenSAFELY platform to examine the safety of COVID-19 therapies that are prescribed in community settings. This was a ‘proof of principle’ study, to show that studying drug safety using routinely captured health data is feasible and effective. Our findings were recently published in the Journal of Infection here.

Why did we do this study?

The management of COVID-19 among high-risk non-hospitalised patients has been improved with the introduction of effective treatments including oral antivirals, paxlovid (nirmatrelvir/ritonavir) and molnupiravir, and intravenous neutralising monoclonal antibodies (nMAB), sotrovimab. These medications have been shown to reduce the risk of developing severe Covid-19 outcomes in patients with underlying health conditions or characteristics that increase their likelihood of severe disease, such as chronic respiratory diseases, cardiovascular disease, and immunocompromising conditions. The safety of these medications has been assessed through clinical trials. However, these trials primarily aim to demonstrate the drugs’ effectiveness and often involve smaller groups of patients, typically without underlying health conditions. As a result, the safety profile may not be fully captured, and rare side effects may be missed.

How did we do this study?

We analysed GP and hospital data for 24 million people in England via the OpenSAFELY platform. We identified all high-risk individuals with COVID-19 who were eligible for treatment. We then examined GP visits, A&E visits and hospital admission occurring within 28 days of treatment. These events were categorised into symptoms or illnesses that were listed in the drug’s Summary of Product Characteristics e.g. diarrhoea or were drug-reactions e.g. anaphylaxis or were immune-mediated events e.g. a new diagnosis of rheumatoid arthritis.

What did we find?

We identified 150,000 patients who were eligible for COVID-19 therapies, and one quarter of them received treatment with either sotrovimab, paxlovid, or molnupiravir. Reassuringly, the number of events was low overall. However, we did find that the rate of events was highest with sotrovimab, showing an increased risk when compared to those eligible for treatment but not receiving any therapy. This increased risk was not observed with paxlovid or molnupiravir. Our work has demonstrated how drug safety can be effectively examined using data from primary and secondary care electronic health records. Working in this way permits a comprehensive understanding of medication safety in a real-world healthcare setting, involving a larger and more diverse patient population and enabling the near-real-time identification of emerging safety signals.

Conclusion

Using the OpenSAFELY platform, we have demonstrated that COVID-19 therapies prescribed in community settings generally have an acceptable safety profile. While an increased risk of adverse events was observed with sotrovimab, this was not seen with paxlovid or molnupiravir, and overall rates of adverse events were low. The most important takeaway from our work is the ability to use routinely collected health data via OpenSAFELY to carry out rapid observational work to improve our understanding of medication safety in real-world settings and inform the roll-out of new treatments.

Get in touch

All of the code used for our analyses is open and reusable here so that other researchers can adapt these methods for their own work. If you have more questions about any of our research, please get in touch via katie.bechman@kcl.ac.uk.