Truth unveiled by time and the marbled definition of D2T-RA: retrospective analysis on the persistence of the difficult-to-treat status among refractory RA patients

The current EULAR definition of difficult-to-treat rheumatoid arthritis (D2T-RA) identifies patients with active disease refractory to multiple treatments at a single time point, without considering the persistence of this condition over time. The study aimed to assess difficult-to-treat rheumatoid arthritis (D2T-RA) over 12 months, considering persistence over time rather than a single time point, in a real-life cohort. In a single-center real-life cohort, demographic and clinic data were cross-sectionally collected for each patient at baseline and retrospectively over the previous 12 months bimonthly. For each timepoint, the prevalence of D2T-RA patients was calculated, and patients meeting the EULAR definition for at least 6 months were defined as persistent D2T-RA (pD2T-RA). Finally, the clinical characteristics associated with the time-based definition of pD2T-RA were analyzed. Among 610 adult RA patients, 104 were refractory to ≥ 2 treatments. Initially, 41.3% met D2T-RA criteria, but only 27.9% fulfilled persistent D2T-RA (pD2T-RA) criteria over 6 months. The pD2T-RA group was associated with male gender, higher HAQ and Charlson Comorbidity Index scores, more failed treatments, and use of non-NSAID analgesics. Logistic regression linked pD2T-RA to higher SDAI and CRP values, and the use of glucocorticoids or analgesics. Chronic use of glucocorticoids was strongly associated with pD2T-RA. The application of a temporal criterion allowed for the selection of a subgroup of pD2T-RA patients who differ from those who meet the definition of D2T-RA only episodically. Chronic use of glucocorticoids was the factor most strongly associated with pD2T-RA status. What is already known about this subject? Since the institution of the D2T-RA definition, many efforts have been made to characterize this subpopulation's prevalence as well as clinical and demographical features. However, no studies have so far faced the temporal maintenance of the D2T-RA status. What does this study add? A definition of persistent or episodic D2T-RA is proposed according to the temporal trajectory of D2T-RA status, resulting in approximately 27% of D2T-RA patients persistently fulfilling the pD2T-RA definition. At each single time point, one-third of D2T-RA patients are represented by episodic D2T-RA patients. How might this impact on clinical practice? Persistent D2T-RA definition may serve to further homogenize the D2T-RA population.