Overcoming Barriers to Remission in Severe Eosinophilic Asthma: Two-Year Real-World Data With Benralizumab.

BACKGROUND: Benralizumab has been reported to lead to clinical remission of severe eosinophilic asthma (SEA) at 1 year in some patients. However, whether this is maintained over a longer term remains unclear. Additionally, the impact of pulmonary and extrapulmonary comorbidities on the ability to meet remission is poorly understood. METHODS: Clinical outcomes including remission of SEA with benralizumab at 1 and 2 years were assessed retrospectively in a real-world UK multi-centre severe asthma cohort. The presence of clinically relevant pulmonary and extrapulmonary comorbidities associated with respiratory symptoms was recorded. Analyses to identify factors associated with the ability to meet remission were performed. RESULTS: In total, 276 patients with SEA treated with benralizumab including 113 patients who had switched from a previous biologic to benralizumab were included. Overall, clinical remission was met in 17% (n = 31/186) and 32% (n = 43/133) of patients at 1 and 2 years, respectively. This increased to 28% at 1 year and 49% at 2 years once patients with pulmonary and/or extrapulmonary comorbidities were excluded. Body mass index (BMI) and maintenance OCS (mOCS) use demonstrated a negative association with clinical remission at 1 (BMI: OR: 0.89, 95% CI: 0.82-0.96, p < 0.01; mOCS: OR: 0.94, 95% CI: 0.89-0.99, p < 0.05) and 2 years (BMI: OR: 0.93, 95% CI: 0.87-0.99, p < 0.05; mOCS: OR: 0.95, 95% CI: 0.89-0.99, p < 0.05). CONCLUSIONS: In this long-term, real-world study, patients with SEA demonstrated the ability to meet and sustain clinical remission when treated with benralizumab. The presence of comorbidities including obesity, which are known to be independently associated with respiratory symptoms, reduced the likelihood of meeting clinical remission.

Implementation of AZD7442 (Tixagevimab/Cilgavimab) COVID-19 Pre-exposure Prophylaxis (PrEP) in the Largest Health Maintenance Organization in Israel: Real-world Uptake and Sociodemographic and Clinical Characteristics Across Immunocompromised Patient Groups.

INTRODUCTION: AZD7442 is a combination of two neutralizing antibodies (tixagevimab/cilgavimab) with demonstrated efficacy in reducing the risk of symptomatic coronavirus disease 2019 (COVID-19) among individuals at high risk of severe COVID-19 ≤ 6 months after administration. On February 15, 2022, the Israeli Ministry of Health (IMoH) authorized the administration of 300 mg AZD7442 as pre-exposure prophylaxis (PrEP) against severe acute respiratory syndrome coronavirus 2 infection among immunocompromised individuals aged ≥ 12 years. This study describes the real-world uptake of AZD7442 in Israel. METHODS: This descriptive, observational study analyzed data from Israel's largest health maintenance organization, Clalit Health Services (CHS). Individuals were assessed for AZD7442 eligibility between February 13 and December 11, 2022, and were included if they were aged ≥ 12 years, had ≥ 1 year of continuous CHS membership, had ≥ 1 moderate or severe immunocompromising condition, and were eligible for AZD7442 per IMoH recommendations during this time frame. RESULTS: Overall, 19,161 AZD7442-eligible individuals with immunocompromising conditions were identified during the study period; 2829 (14.8%) received AZD7442. A higher proportion of individuals receiving AZD7442 were older (aged ≥ 65 years), male, not current smokers and residents in large cities; required more physician visits (> 50 visits); and had ≥ 1 COVID-19 hospitalization over 12 months, while uptake was lowest among ultra-orthodox Jewish individuals. AZD7442 uptake was also higher among individuals with multiple comorbidities (Charlson Comorbidity Index ≥ 5), including hypertension, diabetes and chronic kidney disease. In specific immunocompromised types, AZD7442 uptake was highest among individuals with lung transplantation (41%), primary immunodeficiency (32%), bone marrow transplantation (29%) and multiple myeloma (25%) or those receiving anti-CD20 therapy (26%) and was lowest in individuals with lymphoma (8%). CONCLUSION: These results show AZD7442 uptake among the eligible population of Israel in 2022 was relatively low, at 14.8%. Uptake was generally higher among immunocompromised individuals who may be perceived to be frail or at highest risk of COVID-19 infection and complications, although at 25-41%, further improvements in uptake would be more impactful. These results also indicate there is opportunity to expand AZD7442 uptake across immunocompromised groups and ensure more equitable uptake among some other sociodemographic groups. Overall, this study will help inform and reassess future implementation strategies for vulnerable populations.

Corrigendum to 'Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study' [The Lancet Regional Health - Europe 35 (2023) 100747].

[This corrects the article DOI: 10.1016/j.lanepe.2023.100747.].

Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study.

Background: Immunocompromised individuals are not optimally protected by COVID-19 vaccines and potentially require additional preventive interventions to mitigate the risk of severe COVID-19. We aimed to characterise and describe the risk of severe COVID-19 across immunocompromised groups as the pandemic began to transition to an endemic phase. Methods: COVID-19-related hospitalisations, intensive care unit (ICU) admissions, and deaths (01/01/2022-31/12/2022) were compared among different groups of immunocompromised individuals vs the general population, using a retrospective cohort design and electronic health data from a random 25% sample of the English population aged ≥12 years (Registration number: ISRCTN53375662). Findings: Overall, immunocompromised individuals accounted for 3.9% of the study population, but 22% (4585/20,910) of COVID-19 hospitalisations, 28% (125/440) of COVID-19 ICU admissions, and 24% (1145/4810) of COVID-19 deaths in 2022. Restricting to those vaccinated with ≥3 doses of COVID-19 vaccine (∼84% of immunocompromised and 51% of the general population), all immunocompromised groups remained at increased risk of severe COVID-19 outcomes, with adjusted incidence rate ratios (aIRR) for hospitalisation ranging from 1.3 to 13.1. At highest risk for COVID-19 hospitalisation were individuals with: solid organ transplant (aIRR 13.1, 95% confidence interval [95% CI] 11.2-15.3), moderate to severe primary immunodeficiency (aIRR 9.7, 95% CI 6.3-14.9), stem cell transplant (aIRR 11.0, 95% CI 6.8-17.6), and recent treatment for haematological malignancy (aIRR 10.6, 95% CI 9.5-11.9). Results were similar for COVID-19 ICU admissions and deaths. Interpretation: Immunocompromised individuals continue to be impacted disproportionately by COVID-19 and have an urgent need for additional preventive measures beyond current vaccination programmes. These data can help determine the immunocompromised groups for which targeted prevention strategies may have the highest impact. Funding: This study was funded by AstraZeneca UK.