Trends, variation, and clinical characteristics of recipients of antiviral drugs and neutralising monoclonal antibodies for covid-19 in community settings: retrospective, descriptive cohort study of 23.4 million people in OpenSAFELY

Abstract

ObjectiveTo ascertain patient eligibility status and describe coverage of antiviral drugs and neutralising monoclonal antibodies (nMAB) as treatment for covid-19 in community settings in England.DesignRetrospective, descriptive cohort study, approved by NHS England.SettingRoutine clinical data from 23.4 million people linked to data on covid-19 infection and treatment, within the OpenSAFELY-TPP database.ParticipantsOutpatients with covid-19 at high risk of severe outcomes.InterventionsNirmatrelvir/ritonavir (paxlovid), sotrovimab, molnupiravir, casirivimab/imdevimab, or remdesivir, used in the community by covid-19 medicine delivery units.Results93 870 outpatients with covid-19 were identified between 11 December 2021 and 28 April 2022 to be at high risk of severe outcomes and therefore potentially eligible for antiviral or nMAB treatment (or both). Of these patients, 19 040 (20%) received treatment (sotrovimab, 9660 (51%); molnupiravir, 4620 (24%); paxlovid, 4680 (25%); casirivimab/imdevimab, 50 (<1%); and remdesivir, 30 (<1%)). The proportion of patients treated increased from 9% (190/2220) in the first week of treatment availability to 29% (460/1600) in the latest week. The proportion treated varied by high risk group, being lowest in those with liver disease (16%; 95% confidence interval 15% to 17%); by treatment type, with sotrovimab favoured over molnupiravir and paxlovid in all but three high risk groups (Down's syndrome (35%; 30% to 39%), rare neurological conditions (45%; 43% to 47%), and immune deficiencies (48%; 47% to 50%)); by age, ranging from ≥80 years (13%; 12% to 14%) to 50-59 years (23%; 22% to 23%); by ethnic group, ranging from black (11%; 10% to 12%) to white (21%; 21% to 21%); by NHS region, ranging from 13% (12% to 14%) in Yorkshire and the Humber to 25% (24% to 25%) in the East of England); and by deprivation level, ranging from 15% (14% to 15%) in the most deprived areas to 23% (23% to 24%) in the least deprived areas. Groups that also had lower coverage included unvaccinated patients (7%; 6% to 9%), those with dementia (6%; 5% to 7%), and care home residents (6%; 6% to 7%).ConclusionsUsing the OpenSAFELY platform, we were able to identify patients with covid-19 at high risk of severe outcomes who were potentially eligible to receive treatment and assess the coverage of these new treatments among these patients. In the context of a rapid deployment of a new service, the NHS analytical code used to determine eligibility could have been over-inclusive and some of the eligibility criteria not fully captured in healthcare data. However targeted activity might be needed to resolve apparent lower treatment coverage observed among certain groups, in particular (at present): different NHS regions, ethnic groups, people aged ≥80 years, those living in socioeconomically deprived areas, and care home residents.

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

“…During this treatment period, there was relative clinical equipoise between Paxlovid and sotrovimab (both as first-line options in NHS England guideline) [2]. In addition, eligible patients in this study were required to be non-hospitalised for COVID-19 at treatment initiation (as recorded in COVID-19 therapeutics dataset [9]), and be registered in GP surgeries before treatment. Patients were excluded if they had treatment records of any other antivirals or nMAbs for COVID-19 before receiving the treatment under investigation (n=76).…”

“…No free text data are included. The following linked data were also used for this study: accident and emergency (A&E) attendance and in-patient hospital spell records via Secondary Uses Service (SUS); national coronavirus testing records via the Second Generation Surveillance System (SGSS); and the "COVID-19 therapeutics dataset", a patient-level dataset on antiviral and nMAbs treatments, newly sourced from NHS England, derived from Blueteq software that CMDUs use to notify NHS England of COVID-19 treatments [9].…”

“…The key strengths of the OpenSAFELY platform are the scale, level of detail and completeness of the underlying primary care EHR data and the linkage to multiple COVID-19 relevant national databases with near real-time data update [9,16]. We used a range of analytic methods to examine robustness of results, and were able to carry out extensive adjustments for confounding and exclusions for contraindications given the availability of granular multisource real-world data.…”

“…Validation research directly comparing the effectiveness of sotrovimab and Paxlovid in preventing severe outcomes in routine usage is thus urgently needed for the development of an evidence-based clinical management pathway. Therefore, following the national CMDU rollout of these two first-line medications since February 10, 2022, this real-world observational study aimed to compare the effectiveness of Paxlovid and sotrovimab on preventing severe outcomes in non-hospitalised high-risk COVID-19 patients across England, utilising the near real-time electronic health record (EHR) data in the OpenSAFELY-TPP platform [9]. As an exploratory analysis, we also compared the risks of severe outcomes between Paxlovid users and those treated with molnupiravir [10] (a third-line antiviral in NHS England guideline) during the study period, with the assumption that this group is more comparable to Paxlovid users than untreated controls.…”

Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study

“…In the UK, such treatments were available in community settings from December 2021, reaching ∼33% coverage among individuals with renal disease (including CKD4–5) and solid organ transplant recipients who were infected between December 2021 and April 2022. 31 These treatments may have reduced the risk of disease progression following SARS-CoV-2 infection among a small subset of AZ–AZ–BNT and BNT–BNT–BNT recipients in the three-dose cohort of the present study. 32 …”