Despite the improvement in treatment for people with rheumatoid arthritis (RA), approximately
30% of patients remain symptomatic in the presence of optimised medical therapy, described
as having “difficult-to-treat” (D2T) RA. The average patient with RA has 1.6 other
clinical conditions, which accumulate over time. Comorbidities are increasingly recognised
as key contributors to D2T disease, and are themselves perpetuated by the D2T state.
In this review, we discuss the commonest comorbidities in the context of D2T RA. We
propose the need for a paradigm shift in the clinical and research agenda for comorbidities-
including a need to consider and manage these prior to the development of D2T disease
and not as an afterthought.
