Evaluation of Real-World Safety Surveillance of Targeted Immune-Modifying Therapies Across Immune-Mediated Inflammatory Diseases Using the “Medicines in Acute and Chronic Care in Scotland” Linked Data infrastructure: A Study Protocol and Feasibility Assessment (Preprint)

Abstract

BACKGROUND Immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis, psoriasis, inflammatory bowel disease, and severe asthma, affect millions of people worldwide and often require long-term treatment with targeted immune-modifying therapies such as biologics and Janus kinase (JAK) inhibitors. While these therapies have significantly improved disease outcomes, they are associated with potential safety risks, including serious infections, cardiovascular events, thromboembolism, and malignancies. Traditional pharmacovigilance approaches and clinical trials may not fully capture these rare but clinically important outcomes due to limited follow-up and selective study populations. Linked real-world health data offer opportunities to strengthen post-marketing medicines safety surveillance; however, exposure data for specialist medicines supplied through homecare services are often poorly integrated with national outcome datasets. OBJECTIVE This study aims to evaluate the feasibility of using the Medicines in Acute and Chronic Care in Scotland (MACCS) linked data infrastructure to support real-world safety surveillance of targeted immune-modifying therapies across immune-mediated inflammatory diseases. METHODS A national retrospective cohort study will be conducted using linked routinely collected healthcare datasets within the MACCS environment in Scotland. Adults aged ≥18 years initiating targeted immune-modifying therapies supplied through NHS Homecare Medicines Services between July 2019 and March 2025 will be included using a new-user design with a 6-month washout period. Exposure data will be derived from national homecare medicines supply records and deterministically linked to hospital admissions, cancer registry, critical care, prescribing, and mortality datasets. Primary safety outcomes include serious infections, major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and malignancies. Secondary outcomes include all-cause hospitalisations, critical care admissions, and mortality. Analyses will primarily be descriptive, with incidence rates calculated per 1,000 person-years. Where event counts permit, exploratory Cox proportional hazards models will assess associations between therapy classes and safety outcomes. RESULTS As of March 2025, the MACCS environment includes nationally aggregated Homecare Medicines Services data from six providers representing approximately 98% of the Scottish homecare medicines market. Data linkage with national hospital, cancer, and mortality datasets has been successfully implemented with linkage rates exceeding 99%. Cohort construction using the new-user design has been completed, and preliminary analyses confirm that therapy exposure can be reliably linked to downstream clinical outcomes. Final analyses are ongoing and are expected to be completed by June 2026. CONCLUSIONS This study will provide the first evaluation of whether nationally linked homecare medicines supply data can support systematic safety surveillance of targeted immune-modifying therapies across multiple immune-mediated diseases. Demonstrating the feasibility of this approach could inform the development of scalable real-world pharmacovigilance systems capable of generating timely regulatory safety evidence and supporting next-generation medicines safety monitoring in the UK.