Objective: Despite therapeutic advances and the "treat-to-target" strategy, 5-20% of Rheuma- toid Arthritis (RA) patients fail to achieve treatment goals. The aim of this study was to identify the characteristics and risk factors associated with difficult-to-treat RA.

Patients and Methods: This is a real-life study of patients with RA according to the ACR/EULAR 2010 clas- sification criteria. Sociodemographic, clinical, paraclinical and comorbidity data were collected, as well as the treatments used. Patients were divided into two groups: D2T RA and control group. The results were compared between the two groups. Logistic regression analysis was used to identify risk factors associated with D2T RA.

Results: We included 25 D2T RA patients and 62 non-D2T RA patients. Mean age of patients and disease duration were higher in D2T RA group. Rheumatoid factor seropositivity was higher in the D2T RA group (p = 0.04). They had more active disease (p = 0.001) and more severe functional impairment (p < 0.001). Among ex- tra-articular manifestations, interstitial lung disease was more common in D2T RA patients (p = 0.018). Biologic disease-modifying antirheumatic drugs (bDMARDs) were prescribed more frequently in the D2T RA group and the glucocorticoid dose was higher in this group (p = 0.041). On multivariate analysis, disease activity, disease duration and lung involvement were identified as factors that were associated with D2T RA.

Conclusions: D2T RA can be classified in about one-third of our RA patients. We observed an association be- tween longer disease duration, higher disease activity and rheumatoid factor seropositivity in D2T RA. In addition, lung involvement in the context of RA was more common in this group and may be a contributing factor to an inadequate response to treatment.