PO:06:088 | Are all Difficult-To-Treat RA patients the same? Insights into clinical features and drug discontinuation
Silvia Di Noto1, Cristina Garufi1, Letizia Caruso1, Fulvia Ceccarelli1, Cristiano Alessandri1, Federica Ucci1, Valerio Fiorilli1, Fabrizio Conti1, Francesca Romana Spinelli1 | 1Sapienza University of Rome, Dipartimento di Scienze Cliniche Internistiche, Anestesiologiche e Cardiovascolari, Roma, Italy
Abstract
Aim of the study. D2T rheumatoid arthritis (RA) is a complex condition currently defined by EULAR as failure of +/= 2 biologic or targeted synthetic DMARDs (b/tsDMARDs) with different mechanisms of action, persistent disease activity and significant management challenges. However, this definition, while conceptually valuable, may not fully capture the clinical heterogeneity and multifactorial burden observed in real-world settings. More specifically, it is interesting to explore the clinical features that characterize difficult-to-treat patients, analyze the reasons for discontinuation of b/tsDMARDs and examine characteristics associated with signs of active or progressive disease.
Materials and Methods. Our monocentric cross-sectional study enrolled RA patients fulfilling the 2010 ACR/EULAR criteria and followed for +/= 12 months. D2T patients were classified according to EULAR criteria. We also investigated reasons for b/tsDMARD withdrawal and clinical features possibly associated with D2T status, including: gender, age, disease duration, tender and swollen joint counts, patient global assessments (PGA) and physician global assessments (PhGA), glucocorticoid (GC) dose and duration, C-reactive protein levels and comorbidities (interstitial lung disease, cardiovascular risk factors and events, osteoporosis and fibromyalgia).
Results. We retrospectively evaluated 257 patients (45 males, 212 females) with a mean age of 61 +/- 12 years and median disease duration of 14 years. Among these, 32 patients (12.5%) were classified as D2T. Table 1 summarizes the main clinical characteristics of D2T and non-D2T patients. Fibromyalgia was the only factor significantly associated with D2T status. Figure 1A presents reasons for discontinuation of different lines of b/tsDMARDs. Figure 1B classifies patients based on causes of signs indicative of active disease.
Conclusions. The results of this study aim to differentiate patients classified as D2T based on the reasons that led to the discontinuation of b/ts DMARDs and on the characteristics defining their persistently active disease, highlighting that not all D2T patients can be considered the same.
Materials and Methods. Our monocentric cross-sectional study enrolled RA patients fulfilling the 2010 ACR/EULAR criteria and followed for +/= 12 months. D2T patients were classified according to EULAR criteria. We also investigated reasons for b/tsDMARD withdrawal and clinical features possibly associated with D2T status, including: gender, age, disease duration, tender and swollen joint counts, patient global assessments (PGA) and physician global assessments (PhGA), glucocorticoid (GC) dose and duration, C-reactive protein levels and comorbidities (interstitial lung disease, cardiovascular risk factors and events, osteoporosis and fibromyalgia).
Results. We retrospectively evaluated 257 patients (45 males, 212 females) with a mean age of 61 +/- 12 years and median disease duration of 14 years. Among these, 32 patients (12.5%) were classified as D2T. Table 1 summarizes the main clinical characteristics of D2T and non-D2T patients. Fibromyalgia was the only factor significantly associated with D2T status. Figure 1A presents reasons for discontinuation of different lines of b/tsDMARDs. Figure 1B classifies patients based on causes of signs indicative of active disease.
Conclusions. The results of this study aim to differentiate patients classified as D2T based on the reasons that led to the discontinuation of b/ts DMARDs and on the characteristics defining their persistently active disease, highlighting that not all D2T patients can be considered the same.

Metrics
Citations and online attention from Dimensions, Altmetric and PlumX.
License
Copyright (c) 2026 The Author(s)

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.