POS0671 PROFILE AND MANAGEMENT OF D2T-RA PATIENTS IN THE ITALIAN GISEA REGISTRY
Authors: M. Fornaro, R. F. Caporali, F. Conti, L. Santo, C. Bazzani, A. Scalvini, A. Cauli, F. Cozzini, R. Ramonda, S. Bugatti, M. Govoni, F. P. Cantatore, E. Gremese, S. Guiducci, F. Atzeni, M. S. Chimenti, M. Rossini, R. Gorla, A. Floris, B. Frediani, M. Biggioggero, R. Foti, M. Congia, S. Parisi, A. Corrado, A. Semeraro, M. Morrone, C. Lomater, S. Mancuso, G. Lapadula, G. Ferraccioli, F. Iannone
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Nowadays, numerous therapeutic options are available for patients with rheumatoid arthritis (RA), and the number of patients achieving remission has significantly increased. However, some patients have a disease defined by EULAR as "difficult-to-treat"<sup>1</sup> (D2T), which today represents a new challenge for rheumatologists. <h3>Objectives:</h3> The primary objective was to evaluate the characteristics of the D2T-RA population recorded in the Italian GISEA registry undergoing treatment with b/tsDMARDs. The secondary objective was to assess the effectiveness and changes at 6 and 12 months in disease outcomes, stratifying the analysis by different mechanisms of action. <h3>Methods:</h3> For this study, data from RA patients treated with b/tsDMARDs recorded in the Italian GISEA registry from January 2017 to December 2023 were analyzed. Disease activity scores and patient-reported outcomes (PROs) were recorded at baseline, and at six- and twelve-month follow-up. D2T-RA patients were defined by meeting these three criteria: 1) failure of ≥ 2 b/tsDMARDs (with different mechanisms of action); 2) signs suggestive of active/progressive disease (at least moderate disease activity according to disease activity scores and/or glucocorticoid treatment ≥ 7.5 mg/day prednisone or equivalent); 3) patient VAS (Visual Analogue Scale) pain and/or PtGA (Patient Global Assessment) and/or PhGA (Physician Global Assessment) &gt; 20. The retention rates were estimated using the Kaplan-Meier method and compared with log-rank test, while repeated measures ANOVA (Analysis of Variance) was used to assess changes in disease activity and PROs during follow-up. <h3>Results:</h3> The GISEA cohort included 5251 treatment lines with b/tsDMARDs. We were able to assess the D2T category for 3439 cases at the start of a new treatment. Overall, 1060 (30.8%) patients met all three criteria for D2T-RA, while 2379 (69.2%) patients were not categorized as D2T. Table 1 reports the demographic and clinical characteristics of D2T-RA patients. Patients with D2T-RA showed higher disease activity and PRO scores at baseline. Notably, JAK inhibitors (JAKis) were used more frequently in D2T-RA patients (48.8%) compared to non-D2T-RA patients (33.3%, p&lt;0.05). Globally, the 5-year survival rate was significantly lower for D2T-RA patients compared to those with non-D2T-RA (47.5% vs 62.5%, p&lt;0.001). No significant differences in persistence were observed among the classes of b/tsDMARDs used in D2T-RA (log-rank test: 6.76, p=0.15), with a 5-year survival rate of 38.7% for abatacept, 41.2% for TNFi, 48.1% for IL6r inhibitors, 62.3% for anti-CD20, and 49.6% for JAK inhibitors. Figure 1 shows changes from baseline in disease activity scores and VAS pain in D2T-RA according to b/tsDMARD class. DAS28-ESR was reduced in all b/tsDMARD classes, except for TNFi. CDAI was reduced in all b/tsDMARD classes without any differences among the classes. VAS pain was reduced in all classes. For VAS pain, we observed a significant difference between abatacept and JAK inhibitors, with JAK inhibitors showing greater reduction in VAS pain (p&lt;0.05). Also filgotinib, the latest JAK inhibitor approved onto the market, exhibited a significant decrease on pain perception at both time points. <h3>Conclusion:</h3> Our study provides a snapshot of D2T-RA patients within the GISEA registry. All currently used b/tsDMARDs appear to be effective in this patient cohort. The higher efficacy of JAK inhibitors, particularly in managing pain symptoms in these patients, warrants further investigation. <h3>REFERENCES:</h3> [1] Nagy G, Roodenrijs NMT, Welsing PM, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis. 2021 Jan;80(1):31-35. <h3>Acknowledgements:</h3> We thank Ing. Massimiliano Dellisanti Fabiano Vilardi for his valuable contribution to database creation and management. <h3>Disclosure of Interests:</h3> <b>None declared.</b>