Ab1125 Real-World Safety of Anifrolumab in Patients With Sle: A Multi-National Program of Secondary Database Post Authorization Safety Studies

Background: Anifrolumab is a biological drug approved for the treatment of moderate/severe systemic lupus erythematosus (SLE) in the adult population, and recently included in the EULAR guidelines for the management of SLE. Some post-authorization safety studies have been developed, to fill evidence gaps in a real-world (RW) setting. There are some inherent challenges with these studies, including assessment of moderate/severe SLE disease using RW data, comparison of anifrolumab (an add on medication) to a range of existing treatments and ensuring comparability of cohorts in terms of disease severity. Objectives: To describe a program of anifrolumab post authorization safety studies which utilize RW data aimed at estimating the risk of serious infections, malignancies (SIMA study) and pregnancy-related adverse outcomes (ROSE study) for moderate-severe SLE patients exposed to anifrolumab compared to other standard of care. Methods: SIMA and ROSE are multi-country longitudinal studies utilizing RW data. Cohort selection is based on SLE severity and activity algorithms. These algorithms use recorded information on drug utilization, healthcare resource utilization and the presence of SLE-related disease manifestations to determine disease severity and activity (Figure 1). Additional selection criteria and propensity-score matching will aim to ensure comparability between exposed and unexposed cohorts for each outcome. SIMA uses a prevalent new-user design: patients initiating anifrolumab treatment will be compared with patients exposed to SOC, matched on the time since start of SOC and time-conditional propensity scores. Patients will be followed until the occurrence of the outcomes of interest (Figure 2) or treatment discontinuation (plus an additional 12 months for malignancies to account for a latency period). In ROSE, in utero exposure to anifrolumab and/or SOC will be assessed from date of conception (estimated to be last menstrual period plus 2 weeks to the end of first trimester (for major congenital malformations) or end of pregnancy (for other outcomes) (Figure 2). Follow-up will end at the occurrence of the outcome, end of pregnancy or 1 year after birth, depending on the outcomes. Mother-child linkage will be required to ensure children's follow-up after birth. Results: In both studies, patients' selection and follow-up are country-specific, defined after feasibility assessment, considering the date of anifrolumab market launch in each country. In SIMA, data sources in Denmark, France, Germany, and Spain are included. For serious infections, at least 1,312 patients exposed to anifrolumab matched with 3,936 unexposed patients are required to be selected between March 2022 and April 2025, with follow up lasting till May 2025. For malignancies, at least 3,195 patients exposed to anifrolumab matched with 9,585 unexposed patients are required to be selected between March 2022 and May 2028, with follow up lasting till May 2029. In ROSE, eligible pregnancies from Denmark, Finland, France, Germany, and the United States will be included. Between August 2021 and September 2030, at least 210 anifrolumab exposed pregnancies, and 420 unexposed pregnancies are required to meet the study objectives. In both studies, final sample sizes will vary and are dependent on anifrolumab uptake and study eligibility in the countries of interest. Risk estimates for the outcomes of interest in anifrolumab, and comparator groups will be provided. Additionally, hazard ratios or relative risks will be calculated to present risk of the outcomes with anifrolumab compared with SOC. In addition to data source level analyses, meta-analysis of results from the participating countries for the primary objectives will be combined in a meta-analysis. Conclusion: In addition to the current favorable safety profile of anifrolumab from the clinical development program, these post authorization safety studies will provide valuable RW safety information on serious infections and malignancies and fill evidence gaps on use in pregnancy. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Sofia Correia Funding from AstraZeneca to my employer IQVIA for overall study execution, Urmeli Katus Funding from AstraZeneca to my employer IQVIA for overall study execution, Shabeena Huda AstraZeneca, Pranita Kabadi AstraZeneca, AstraZeneca, AstraZeneca, Mickael Arnaud Funding from AstraZeneca to my employer IQVIA for overall study execution, Ana Cristina Santos Funding from AstraZeneca to my employer IQVIA for overall study execution, Leyla Nunez Funding from AstraZeneca to my employer IQVIA for overall study execution, Julia Pietila Funding from AstraZeneca to my employer IQVIA for overall study execution, Muriel Lobier Funding from AstraZeneca to my employer IQVIA for overall study execution, Jonatan Hedberg AstraZeneca, AstraZeneca, Stefan Franzen AstraZeneca, AstraZeneca, Robert Corbe AstraZeneca, AstraZeneca, Dony Patel Funding from AstraZeneca to my employer IQVIA for overall study execution, Eileen Dareng AstraZeneca, AstraZeneca.