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IntroductionThere is limited real-world evidence describing the effectiveness of early treatments for Coronavirus disease 2019 (COVID-19) during the period where Omicron was the dominant variant. Here we describe characteristics and acute clinical outcomes in patients with COVID-19 treated with a monoclonal antibody (mAb; presumed to be sotrovimab) across six distinct periods covering the emergence and subsequent dominance of Omicron subvariants (BA.1, BA.2 and BA.5) in England.MethodsRetrospective cohort study using data from Hospital Episode Statistics database between 1stJanuary – 31stJuly 2022. Included patients were aged ≥12 years and received a mAb delivered by a National Health Service (NHS) hospital as a day-case, for which the primary diagnosis was COVID-19. Patients were presumed to have received sotrovimab on the basis of available NHS data showing that 99.98% of individuals who received COVID-19 treatment during the period covered by the study were actually treated with sotrovimab. COVID-19-attributable hospitalisations were reported overall and across six distinct periods of Omicron sub-variant prevalence. A multivariate Poisson regression model was used to estimate incidence rate ratios for each period. Subgroup analyses were conducted in patients with severe renal disease and active cancer.ResultsIn total, 10,096 patients were included. The most common high-risk comorbidities were Immune-Mediated Inflammatory Disorders (43.0%;n= 4,337), severe renal disease (14.1%;n= 1,422), rare neurological conditions (10.4%;n= 1,053) and active cancer (9.0%;n= 910). The proportions of patients with a COVID-19-attributable hospitalisation was 1.0% (n= 96), or with a hospital visit due to any cause was 4.6% (n= 465) during the acute period. The percentage of patients who died due to any cause during the acute study period was 0.3% (n= 27). COVID-19-attributable hospitalisation rates were consistent among subgroups and no significant differences (p-values ranged from 0.13 to 0.64) were observed across periods of Omicron subvariants.ConclusionLow levels of COVID-19-attributable hospitalisations and deaths were recorded in mAb-treated patients. Results were consistent for patients with severe renal disease and active cancer. No evidence of differences in hospitalisation rates were observed whilst Omicron BA.1, and BA.2 or BA.5 subvariants were predominant, despite reported reductions in in vitro neutralisation activity of sotrovimab against BA.2 and BA.5.

IntroductionThere is limited real-world evidence surrounding the effectiveness of early, mild-to-moderate COVID-19 treatments following the emergence and dominance of Omicron SARS-CoV-2 subvariants. Here, characteristics and acute clinical outcomes are described for patients with COVID-19 treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or patients at highest risk per NHS criteria but who were untreated.MethodsRetrospective cohort study of non-hospitalised patients who received early treatment for, or were diagnosed with, COVID-19 between 1 December 2021 and 31 May 2022, using data from the Discover dataset in north-west London. Patients were included if aged ≥12 years and treated with sotrovimab, nirmatrelvir/ritonavir or molnupiravir, or were untreated but expected to be eligible for early treatment per NHS highest-risk criteria at time of diagnosis. Outcomes were reported for 28 days from COVID-19 diagnosis (index). Subgroup analyses were conducted in patients with advanced renal disease, those aged 18–64 and ≥65 years and by period of Omicron BA.1, BA.2 and BA.5(post-hocexploratory analysis) predominance.ResultsA total of 696 patients prescribed sotrovimab, 337 prescribed nirmatrelvir/ritonavir, 470 prescribed molnupiravir and 4,044 eligible high-risk untreated patients were included. A high proportion of patients on sotrovimab had advanced renal disease (29.3%), ≥3 high-risk comorbidities (47.6%) and were aged ≥65 years (36.9%). In total, 5/696 (0.7%) patients on sotrovimab, ConclusionPatients who received sotrovimab appeared to show evidence of multiple comorbidities that may increase risk of severe COVID-19. Low hospitalisation rates were observed for all treated cohorts across subgroups and periods of predominant variants of concern. These descriptive results require confirmation with comparative effectiveness analyses adjusting for differences in underlying patient characteristics.Key pointsWhy carry out this study?There is limited real-world evidence surrounding early, mild-to-moderate COVID-19 treatments, particularly during Omicron subvariant dominance periods, and the UK National Institute for Health and Care Excellence has recommended more is gathered.We described patient characteristics and clinical outcomes among patients treated with sotrovimab, nirmatrelvir/ritonavir, molnupiravir or who met the highest-risk eligibility criteria but were untreated.What was learned from the study?Sotrovimab was often utilised amongst more elderly and at-risk patients, such as those with advanced renal disease, than patients treated with nirmatrelvir/ritonavir or molnupiravir.We found that hospitalisation rates were low across all treated cohorts.For patients treated with sotrovimab, clinical outcomes appeared consistent when observed across the age subgroups and Omicron subvariant periods, as well as among patients with advanced renal disease.

ObjectiveTo assess use of bone-targeting agents (BTA) in patients with confirmed bone metastases (BM) from breast cancer (BC), non-small cell lung cancer (NSCLC) or prostate cancer (PC).DesignRetrospective cohort study.SettingRegional hospital-based oncology database of approximately 2 million patients in England.ParticipantsPatients aged ≥18 years with a diagnosis of BC, NSCLC or PC as well as BM between 1 January 2007 and 31 December 2018, with follow-up to 30 June 2020 or death; BM diagnosis ascertained from recorded medical codes and unstructured data using natural language processing (NLP).Main outcomes measuresInitiation or non-initiation of BTA following BM diagnosis, time from BM diagnosis to BTA initiation, time from first to last BTA, time from last BTA to death.ResultsThis study included 559 BC, 894 NSCLC and 1013 PC with BM; median age (Q1–Q3) was 65 (52–76), 69 (62–77) and 75 (62–77) years, respectively. NLP identified BM diagnosis from unstructured data for 92% patients with BC, 92% patients with NSCLC and 95% patients with PC. Among patients with BC, NSCLC and PC with BM, 47%, 87% and 88% did not receive a BTA, and 53%, 13% and 12% received at least one BTA, starting a median 65 (27–167), 60 (28–162) and 610 (295–980) days after BM, respectively. Median (Q1–Q3) duration of BTA treatment was 481 (188–816), 89 (49–195) and 115 (53–193) days for patients with BC, NSCLC and PC. For those with a death record, median time from last BTA to death was 54 (26–109) for BC, 38 (17–98) for NSCLC and 112 (44–218) days for PC.ConclusionIn this study identifying BM diagnosis from both structured and unstructured data, a high proportion of patients did not receive a BTA. Unstructured data provide new insights on the real-world use of BTA.

Introduction/Background Clinical trials in Epithelial Ovarian Cancer (EOC) frequently examine treatment at a particular phase of the patient’s disease trajectory. Few major studies have examined the management of patients from diagnosis to death. This international network was developed to compare treatment sequencing and outcomes from six centres across Europe and South Korea. Methodology This retrospective cohort study used longitudinal data collected from electronic medical records from 6 European and South Korean treatment centres. A standard protocol & common data model was developed to capture consistent data for patients diagnosed between January 2012 and December 2018, with a minimum of 12 months follow-up. Full treatment data was collected and categorized in programmes of care based on exemplar patient narratives. An extensive data harmonization process was implemented to ensure different country and site medical records were interpreted in a common manner. Overall survival (OS) and time to next treatment (TTNT) were estimated using Kaplan Meier methodology and outcomes stratified by categories of interest. Each site analysed their own EMR data and shared aggregated results for comparison. Results Table 1 demonstrates patient characteristics from six sites. In total the overall study cohort includes 2889 patients. Median age for each centre ranged from 53 to 67 years. The majority of patients were FIGO stage III (range 31% to 66%) and high-grade serous morphology (52% to 69.9%) Additional data on treatment pathways and outcomes for each centre will be presented. Conclusion Preliminary analysis from this network suggests a consistent profile of adults treated for EOC across most contributing treatment centres in Europe, but with some substantial differences compared to patients treated at centres in South Korea and Romania. The establishment of a common data model between sites across five different countries allows for detailed exploration of the factors influencing differences in patient management and treatment outcomes in ovarian cancer patients. Disclosures Sue Cheeseman: I receive consultancy fees from IQVIA Bethany Levick: I am an employee of IQVIA Eunji Nam: I have no conflict of interest to disclose Dongkyu Kim: I have no conflict of interest to disclose Roman Rouzier: I have no conflict of interest to disclose Claire Bonneau: I have no conflict of interest to disclose Paul Kubelac: served on a speaker’s bureau for Roche, Bristol-Myers Squibb, AstraZeneca, Novartis. Patriciu Achimas-Cadariu: I have no conflict of interest to disclose Jean-Marc Classe: I have no conflict of interest to disclose Francois Bocquet: I have no conflict of interest to disclose Sven Becker: I have no conflict of interest to disclose Mariana Guergova-Kuras: I am an employee of IQVIA Geoff Hall: I receive grant support and consultancy fees from IQVIA

e13554 Background: The value of real-world evidence derived from the care of patients managed outside the context of clinical trials is well recognised. However, the ability to link data from multiple centres, especially those from different countries, is complicated by complex legal and information governance differences. The Oncology Evidence Network is a collaboration of large hospital centres, with strong clinical informatics capabilities in six countries in Europe and Asia working with the support of an industrial partner to provide high quality, real world data reflecting routine clinical care. We have developed an efficient workflow based on a study-specific common data model (CDM) clinically validated at each site and analysed with a single analysis script, which embeds a set of data quality rules. Local implementation allows each centre to generate analytical outputs aligned across the different sites without the need for any patient level data to leave the participating site. This approach has been designed and tested in Epithelial Ovarian Cancer (EOC) patients. Methods: A CDM was agreed using expert advisors from each centre. Clinical alignment was achieved through iterative assessment of clinical vignettes, to ensure common definitions of clinical assessment, prognosis, and treatment algorithms in EOC patients. A data guide detailing variable level derivations and validation rules, general data coding principles, and conversions/codes from international coding systems was developed. The analysis scripts were implemented as a bespoke package (OpenOvary) in R. The package includes functions to validate the data against the CDM, and generate a standard output including tables, numerical summaries and Kaplan-Meier analysis of progression and overall survival. Results: 2,925 patient records from 6 centres across 6 countries were included in the study with 27 key data items curated by each centre. Treatment data is available detailing relevant surgical procedures and their outcomes, and regimens of SACT throughout patients’ care from diagnosis to death. Data completeness was generally high for key data items, with missing data ranging from 0-16% for FIGO stage at diagnosis and 0-14% for tumour morphology. The CDM and R script will be made publicly available for other centres to adopt and facilitate analysis of their local data. Conclusions: This collaboration has brought together a substantial body of data describing the care and outcomes for EOC patients. A CDM and flexible shared analysis approach enabled unified analysis and reporting whilst avoiding the transfer of patient level data and its pooling into a common database. The process of clinical and data alignment has generated a replicable model for rapid extension to other study centres to join the EOC study, or application to other disease areas.

5531 Background: Few major studies have examined and compared the management and outcomes of patients from diagnosis to death between countries. We have established an international collaboration across Europe and South Korea to compare treatment and outcomes in Epithelial Ovarian Cancer (EOC). Methods: Patients diagnosed with EOC between January 2012 and December 2018 (age ≥18), were included for analysis. Data from medical records from five European and a single South Korean treatment centre were extracted, standardised to a common data model and analysed at each centre using a common script developed in R. Time to each progression/recurrence event (defined as time to next treatment) and overall survival have been estimated using Kaplan Meier methodology and outcomes stratified by categories of interest. Changes in the use of anti-cancer therapies over time and the incidence of BRCA mutations and incidence/timing of second breast cancers have also been examined. Results: A total cohort of 2925 patients was identified with a median age at each centre of 53 to 67 years. Advanced disease (FIGO stage III - IV) (range 57% to 84%) and high-grade serous morphology (38% to 70%) were most common at each centre. The timing of surgery (primary, interval debulking or delayed) and the proportion of patients undergoing surgery varied with stage. Patients with stage I disease where most likely to undergo surgery (range 73% to 100%) and stage IV the least (range 39% to 84%). Median overall survival for high grade serous cancers ranged from 1.9 to 4.9 years, and for the whole cohort from 2.1 to 5.5 years. Median time to next treatment at first relapse for the whole cohort ranged from 14 to 22 months. Second breast cancers were noted in 6 to 17% of patients and the majority of these occurred before the diagnosis of EOC at a median time of 96 to 118 months prior to diagnosis of EOC. Additional data on treatment pathways, BRCA status and outcomes by line of therapy for each centre will be presented. Conclusions: Preliminary analysis of results across this network suggests a variation in patient populations between sites and substantial differences in both treatments and outcomes. The establishment of a common data model and the use of a common analytic script between sites across six different countries allows for detailed exploration of the factors influencing differences in patient management and treatment outcomes in ovarian cancer patients.

Background An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. The objective of this study was to determine the prevalence of epilepsy in onchocerciasis endemic areas in the Democratic Republic of the Congo (DRC) and investigate whether a higher annual intake of Ivermectin was associated with a lower prevalence of epilepsy. Methodology/Principle findings Between July 2014 and February 2016, house-to-house epilepsy prevalence surveys were carried out in areas with a high level of onchocerciasis endemicity: 3 localities in the Bas-Uele, 24 in the Tshopo and 21 in the Ituri province. Ivermectin uptake was recorded for every household member. This database allowed a matched case-control pair subset to be created that enabled putative risk factors for epilepsy to be tested using univariate logistic regression models. Risk factors relating to onchocerciasis were tested using a multivariate random effects model. To identify presence of clusters of epilepsy cases, the Kulldorff's scan statistic was used. Of 12, 408 people examined in the different health areas 407 (3.3%) were found to have a history of epilepsy. A high prevalence of epilepsy was observed in health areas in the 3 provinces: 6.8–8.5% in Bas-Uele, 0.8–7.4% in Tshopo and 3.6–6.2% in Ituri. Median age of epilepsy onset was 9 years, and the modal age 12 years. The case control analysis demonstrated that before the appearance of epilepsy, compared to the same life period in controls, persons with epilepsy were around two times less likely (OR: 0.52; 95%CI: (0.28, 0.98)) to have taken Ivermectin than controls. After the appearance of epilepsy, there was no difference of Ivermectin intake between cases and controls. Only in Ituri, a significant cluster (p-value = 0.0001) was identified located around the Draju sample site area. Conclusions The prevalence of epilepsy in health areas in onchocerciasis endemic regions in the DRC was 2–10 times higher than in non-onchocerciasis endemic regions in Africa. Our data suggests that Ivermectin protects against epilepsy in an onchocerciasis endemic region. However, a prospective population based intervention study is needed to confirm this., Author summary An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. Between July 2014 and February 2016, house-to-house epilepsy prevalence surveys were carried out in the Bas-Uele, Tshopo and Ituri province of the Democratic Republic of the Congo, in areas with a high level of onchocerciasis endemicity. Of 12, 408 people examined in the different health areas 407 (3.3%) were found to have a history of epilepsy. A nested case control analysis demonstrated that before the appearance of epilepsy, compared to the same life period in controls, persons with epilepsy were around two times less likely to have taken Ivermectin than controls. Our data suggests that Ivermectin protects against epilepsy in an onchocerciasis endemic region. However, a prospective population based intervention study is needed to confirm this.

Background An increased prevalence of epilepsy has been reported in many onchocerciasis endemic areas. Objective To determine the prevalence and distribution of epilepsy in an onchocerciasis endemic region in the Democratic Republic of the Congo (DRC). Design/Methods An epilepsy prevalence study was carried out in 2014, in two localities of the Bas-Uélé district, an onchocerciasis endemic region in the Orientale Province of the DRC. Risk factors for epilepsy were identified using a random effects logistic regression model and the distribution of epilepsy cases was investigated using the Moran’s I statistic of spatial auto-correlation. Results Among the 12,776 individuals of Dingila, 373 (2.9%) individuals with epilepsy were identified. In a house-to-house survey in Titule, 68 (2.3%) of the 2,908 people who participated in the survey were found to present episodes of epilepsy. Epilepsy showed a marked spatial pattern with clustering of cases occurring within and between adjacent households. Individual risk of epilepsy was found to be associated with living close to the nearest fast flowing river where blackflies (Diptera: Simuliidae)–the vector of Onchocerca volvulus–oviposit and breed. Conclusions The prevalence of epilepsy in villages in the Bas-Uélé district in the DRC was higher than in non-onchocerciasis endemic regions in Africa. Living close to a blackflies infested river was found to be a risk factor for epilepsy., Author Summary An increased prevalence of epilepsy has been reported in many onchocerciasis (river blindness) endemic areas. In 2014, an epilepsy prevalence study was conducted in Dingila and Titule, two localities within the onchocerciasis endemic Orientale province of the Democratic Republic of Congo, both within the Bas-Uélé district. The prevalence of epilepsy was 2.9% in Dingila, and 2.3% in Titule. This is much higher than the epilepsy prevalence in non-onchocerciasis endemic regions in Africa. Epilepsy cases were clustered within and between adjacent households. Living close to a river infested with blackflies (the main vector of Onchocerca microfilariae) was found to be a risk factor for epilepsy.