Clinical and non-clinical outcomes of patients with early rheumatoid arthritis

Abstract

Background Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that can lead to disability and premature mortality, with infections being one of the most common causes of adverse outcomes. In 2020, it was estimated that 17.6 million people worldwide were living with RA (1). Achieving disease remission is the primary treatment goal, as it helps to minimise symptoms and prevent joint deterioration (2). While extensive research has been conducted on established RA, large registries as the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) primarily focus on biologic/targeted therapies and their associated health outcomes (3, 4). In contrast, there is limited data on early-onset RA in the United Kingdom (UK), creating a gap in understanding how treatment strategies influence both remission rates and infection risks in newly diagnosed patients. The National Early Inflammatory Arthritis Audit (NEIAA) is one of the most comprehensive datasets in the UK, providing real-world insights into early RA, offering valuable data to improve contemporary patient care.

Objective This PhD thesis focuses on treatments and outcomes in early RA, addressing key themes that are central to optimal patient care: the safety of initial treatment strategies, the impact of health inequalities, the risks associated with infections, and how patients with recently diagnosed RA were affected by the Coronavirus Disease 2019 (COVID-19) pandemic. By combining systematic analyses with real-world data, the thesis aims to provide practical insights that can influence clinical practice and guide policy decisions.

Methods I used systematic review, network meta-analyses, and large-scale cohort studies to address my objectives. The systematic review synthesises evidence on treatment safety in early RA and the use of network meta-analysis allows comparisons of treatments not directly studied in head-to-head trials. In the subsequent chapters, I use observational cohort data, NEIAA. I employed different statistical techniques, including survival analyses, adjustment for confounders and incorporation of multiple imputation for missing data.

Results The systematic review revealed that biologic monotherapy was associated with higher rates of serious adverse events compared to methotrexate-based or steroid-based strategies. Unlike findings in established RA, corticosteroid use did not lead to significantly worse outcomes in early disease. This challenges conventional assumptions and supports the cautious use of steroids in remission induction. A key chapter, that was not originally planned in the thesis at the outset, examines COVID- 19 admissions and mortality in patients with early inflammatory arthritis using linked national datasets. The findings are reassuring, where there was no excess mortality compared to the general population, and initial treatment strategies were not major drivers of severe COVID-19 outcomes. Instead, patient-specific factors including age, comorbidities, and baseline functional impairment were more predictive, suggesting that wider public health measures and patient monitoring should be the focus in future pandemics. The analysis of ethnicity and health inequalities, which was also motivated by other research emerging during the COVID-19 pandemic, revealed concerning disparities. Patients from ethnic minority backgrounds experienced lower remission rates, even after adjusting for deprivation. These results highlight ongoing gaps in equitable care and underscore the need for targeted interventions. My final result chapter explored infection risks among patients in the NEIAA cohort. While severe baseline disease and steroids use were associated with a higher risk of infection- related hospitalisations (steroids risk in unadjusted models only), conventional synthetic disease modifying antirheumatic drugs (csDMARDs) did not significantly increase infection risks. This provides valuable guidance for infection risk management in clinical settings.

Conclusion This thesis highlights the importance of tailoring RA treatments to individual patient profiles while addressing broader systemic issues, like inequality and access to services. It underscores that effective treatment must balance safety, patient characteristics, and real- world feasibility.