Challenges and insights in managing difficult-to-treat rheumatoid arthritis: real-world clinical perspectives

The treatment options for rheumatoid arthritis (RA) have expanded with the availability of biological and targeted synthetic disease-modifying anti-rheumatic drugs. Despite all these developments and treatments, an important group of patients remain symptomatic and have not achieved clinical remission. The terminology "difficult-to-treat" (D2T) has been developed to describe this group. This study aimed to determine the frequency of D2T RA among our patients according to the EULAR 2021 definition of D2T RA and to identify the differences in demographic and disease characteristics, contributing factors, and disease burden.

The study included 302 consecutive patients diagnosed with RA according to the 2010 ACR criteria. These patients were categorised into the D2T and non-D2T RA groups. Risk factors independently associated with D2T RA were identified using logistic regression analysis.

Of the 302 patients (mean age, 56.5 years, 80.1% female, 75% seropositive), 27 (8.9%) had D2T RA. Those with D2T RA had a lower age at diagnosis and longer disease duration and showed significantly higher rates of peripheral erosion, Sjögren's syndrome, extra-articular manifestations, and PtGA-PhGA discordance, together with high disease activity scores. Furthermore, the median number of comorbidities and concomitant fibromyalgia was significantly higher in the D2T RA group. In the multiple regression analysis, D2T RA was independently associated with higher HAQ-DI, RF levels, and concomitant fibromyalgia.

D2T RA requires more intensive management, and patients with D2T RA have higher disease activity, poorer functional status, and quality of life than those without D2T RA.