Uptake of monoclonal antibodies and antiviral therapies for COVID-19 in Scotland.

SARS-CoV-2 has kept evolving since it was first detected in 2019. Virus mutations have affected transmissibility, virulence, and the effectiveness of vaccines and COVID-19 therapeutics. In Scotland, treatments recently made available for use in patients with COVID-19 are sotrovimab, a neutralising monoclonal antibody that targets SARS-CoV-2 spike proteins, and SARS-CoV-2-specific antiviral drugs that inhibit viral replication. The latter includes nirmatrelvir–ritonavir (Paxlovid, Pfizer), which inhibits viral protease, and molnupiravir, which increases viral RNA mutagenesis. Current guidance advises that these drugs be offered to vulnerable patients within 5–7 days of presenting with mild-to-moderate COVID-19 to prevent disease progression.1Department of Health and Social CareInterim clinical commissioning policy: neutralising monoclonal antibodies or antivirals for non-hospitalised patients with COVID-19.https://www.england.nhs.uk/coronavirus/publication/interim-clinical-commissioning-policy-neutralising-monoclonal-antibodies-or-antivirals-for-non-hospitalised-patients-with-covid-19/Date: Nov 30, 2022Date accessed: October 17, 2022Google Scholar The choice of treatment is mainly based on pre-existing conditions and concurrent drug treatment. Other more established therapeutics are also used in an inpatient setting to improve outcomes in patients who are hospitalised with severe COVID-19.2Department of Health and Social CareInterim clinical commissioning policy: IL-6 inhibitors (tocilizumab or sarilumab) for hospitalised patients with COVID-19 (adults).https://www.england.nhs.uk/coronavirus/documents/interim-clinical-commissioning-policy-il-6-inhibitors-tocilizumab-or-sarilumab-for-hospitalised-patients-with-covid-19-adults-2/Date: Nov 28, 2022Date accessed: November 28, 2022Google Scholar We sought to assess the uptake of these novel treatments and whether they are being used as recommended across Scotland.3National Institute for Health and Care ExcellenceCOVID-19 rapid guideline: managing COVID-19 (version 27.6).https://www.nice.org.uk/guidance/ng191/resources/covid19-rapid-guideline-managing-covid19-pdf-51035553326Date: Nov 11, 2022Date accessed: November 11, 2022Google Scholar Data on COVID-19 therapeutics were extracted from the Hospital Electronic Prescribing and Medicines Administration system from six of the 14 Scottish Health Boards; for the remaining eight Health Boards that did not have this system in place, we requested these data on a weekly basis. We obtained data dating back from Sept 26, 2022 (with different end dates per Health Board), to Dec 21, 2021 (when treatment pathways for these novel therapeutics were first implemented in Scotland). These therapeutics records were then linked by pseudoanonymised patient identifier to data on Scotland's national COVID-19 surveillance platform, EAVE II.4Mulholland RH Vasileiou E Simpson CR et al.Cohort profile: early pandemic evaluation and enhanced surveillance of COVID-19 (EAVE II) database.Int J Epidemiol. 2021; 50: 1064-1074Google Scholar Patients were categorised by whether they received treatment (administered or prescribed) during a hospital admission. For patients who were prescribed multiple therapies (known as a treatment cocktail) the initiation date was considered to be the date of the first treatment administration or prescription. After excluding 66 patients for whom therapeutic data were missing, we identified 14 464 treated patients. Of these, 11 465 (79·3%) patients had been treated in the outpatient setting, 3056 (26·7%) of whom were given sotrovimab (monotherapy), whereas 5436 (47·4%) were given nirmatrelvir–ritonavir, 2793 (24·4%) molnupiravir, and 180 (1·6%) multiple therapies. The distribution of therapeutics used each week is shown in the figure. 28 660 people were estimated to have met the treatment eligibility criteria according to COVID-19 diagnosis and high-risk comorbidities and were therefore included in the denominator for the treated proportion analyses. Symptom severity was not routinely recorded (for example at the point of contact with triage, known as a Flow Navigation Centre), and therefore patients who were ineligible for treatment because they were asymptomatic or had mild symptoms could not be excluded from the denominator. We were unable to identify patients who did not contact a Flow Navigation Centre at all or those who declined to be treated. Overall, 40·0% of patients who were eligible to receive monoclonal antibodies or antivirals were treated in the outpatient setting. Treatment with these drugs was lowest in patients aged 18 years or younger (20·3% in eligible patients aged 12–18 years compared with 29·6–47·3% in patients aged 30–89 years) as well as in patients aged 90 years or older (23·0%), patients living in deprived areas (30·1% in the most deprived compared vs 47·7% in the least deprived quintiles), and patients who had received fewer than the recommended number of vaccine doses (11·3–33·5% in patients who had received fewer than four vaccine doses vs 97·7% in those who had received at least five doses vs 77·1% in those who had received four doses; appendix p 2). Focusing on individual groups of at-risk patients, very low proportions (22·5%) of eligible individuals who were identified as having rheumatoid arthritis or systemic lupus erythematosus were treated with monoclonal antibodies or antivirals, whereas 71·7% of patients who had received a stem-cell transplant were treated. The proportion of patients treated was also low in those identified as having HIV/AIDS (21·9%), although current CD4 count was not investigated, which would need to be sufficiently low (<350 cells per μL) for an individual to be considered at risk. 26·8–61·2% of patients with other comorbidities received treatment (appendix pp 2–3). Overall, 98·5% of all individuals treated in an outpatient setting were treated within 5 days of diagnosis, the lowest target in the treatment guidelines.3National Institute for Health and Care ExcellenceCOVID-19 rapid guideline: managing COVID-19 (version 27.6).https://www.nice.org.uk/guidance/ng191/resources/covid19-rapid-guideline-managing-covid19-pdf-51035553326Date: Nov 11, 2022Date accessed: November 11, 2022Google Scholar Treatment was initiated a median of 1 day after diagnosis for nirmatrelvir–ritonavir (IQR 1–2, 99th percentile 5 days, maximum 20 days), and a median of 2 days after diagnosis for molnupiravir (2–3, 8, 21), sotrovimab (2–3, 5, 17), and treatment cocktails (1–2, maximum 5 days). Identifiable diagnosis dates were available of 76·3% of patients given nirmatrelvir–ritonavir, 61·5% given molnupiravir, 47·5% given sotrovimab, and 46·1% given treatment cocktails, probably because positive lateral flow tests were not recorded in all cases. The criteria met to ascertain eligibility for treatment could not be identified for 28·2% of those who received outpatient care. The estimation of comorbidities (primarily cancer) was limited by the availability of cancer therapy and diagnostic data. Additionally, only general or acute inpatient records (including from the Rapid Preliminary Inpatient Data dataset) were available (appendix p 1), whereas records from other inpatient departments, such as maternity and mental health departments, were not available. Despite these limitations, such a thorough data collection process enables continued monitoring of the use of COVID-19 therapeutics in community settings in Scotland, which will be important as data from PANORAMIC (ISRCTN30448031) and other trials emerge. Identifying patients who might otherwise be missed can help to boost early treatment, improve access to care, and reduce the need for acute, inpatient care. In summary, we show that around half of individuals who we estimate to have been eligible received monoclonal antibodies or antivirals for the treatment of COVID-19 in Scotland, but the overwhelming majority of those who received treatment did so within the recommended time limit. There is a clear need to increase awareness and uptake of these treatment options in individuals who are at high risk of severe COVID-19 outcomes—particularly those who are younger than 18 years, are socioeconomically disadvantaged, have HIV and particular rheumatological conditions, or have suboptimal protection from vaccination. Data approvals were obtained from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), and the Public Benefit and Privacy Panel for Health and Social Care (HSC-PBPP; 0920-0279). The data are stored in the Public Health Scotland Trusted Research Environment. To access these individual-level, confidential health-care data, researchers should apply to the HSC-PBPP (https://www.informationgovernance.scot.nhs.uk/pbpphsc/). AS has served on COVID-19 advisory groups for the UK and Scottish Governments and for AstraZeneca, all of which have been unremunerated. AS holds a research grant on the effectiveness and safety of monoclonal antibodies from GSK. This Correspondence was supported by the Medical Research Council (UKRIMC_PC19075) and the National Institute for Health and Care Research (NIHR135575). We thank Lynn Laidlaw and Kamil Sterniczuk for their contributions to the development of this Correspondence. For the purpose of open access, the authors have applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this Correspondence. Download .pdf (.21 MB) Help with pdf files Supplementary appendix