Exploring innovations and opportunities in the management of rheumatoid arthritis: balancing therapeutic and disease-related risks

Abstract

This thesis examines the treatment, management, and long-term outcomes of patients with early rheumatoid arthritis (RA) and undifferentiated arthritis, drawing primarily from the Dutch BeSt and IMPROVED clinical trials.

The first section challenges the widely accepted "window of opportunity" concept, finding no evidence of an exponentially declining treatment window, while demonstrating that fast-acting combination therapy achieves better outcomes than slow-acting monotherapy. It further shows that poor prognostic factor-based biological treatment escalation offers no long-term advantage over stepwise conventional therapy.

The second section addresses glucocorticoid (GC) dose optimisation, finding that higher initial GC doses produce greater early clinical improvement without significantly increased toxicity. A prospective evaluation of AI-assisted abstract screening demonstrated promising efficiency gains but insufficient reliability for independent use in complex systematic reviews. The third section investigates long-term outcomes, demonstrating that disease activity (rather than GC use) drives diabetes risk in RA patients. Finally, joint damage repair was observed in a small proportion of patients, though it remained rare, unpredictable, and occasionally unstable. Collectively, the findings advocate for personalised, evidence-based treatment strategies, timely intervention, and adequate disease control to optimise both short- and long-term patient outcomes.