THU0151 COMPARISON BETWEEN THREE PROPOSED DEFINTIONS OF DIFFICULT-TO-TREAT/REFRACTORY RHEUMATOID ARTHRITIS IN A COHORT OF BDMARD-TREATED PATIENTS
Authors: Francesca Ometto, Lara Friso, Davide Astorri, Costantino Botsios, Bernd Raffeiner, Andrea Doria
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> A definition of difficult-to-treat/refractory rheumatoid arthritis (RA) (RRA) has not been established yet, nevertheless, RRA is commonly associated with the resistance to multiple bDMARDs [1,2,3]. <h3>Objectives</h3> The objective was to evaluate the rate of RRA according to three definitions, the agreement between the definitions and major determinants of such definitions in a large monocentric cohort of RA patients. <h3>Methods</h3> We included RA patients treated with any bDMARD (&gt;=1 year), who started bDMARDs after 2001. Considered definitions of RRA were: B-RAA, according to Buch [3], failure of &gt;=1 anti-cytokine (TNF and/or IL6 ihnibitor) and &gt;=1 cell-targeted (B-cell and/or T-cell ihnibitor) bDMARD; KF-RAA, according to Kearsley-Fleet [2], exposed to &gt;=3 bDMARDs classes; DH-RRA, according to de Hair [1], signs and/or symptoms suggestive of inflammatory RA activity (in the study we assumed DAS28&gt;=3.2 or extra-articular manifestations) and failure of &gt;=1 csDMARD and &gt;=2 bDMARDs. Agreement was measured with Cohen's kappa. To assess variables independently associated with RRA, multivariate regression analysis was used including variables achieving p&lt;0.10 in univariate analysis. <h3>Results</h3> Patients included in the study were 572. B-RRA was observed in 165 (28.8%), KF-RRA in 96 (16.8%) and DH-RRA in 57 (10.0%). DH-RRA was the most stringent definition. Agreement between the definition was fair: DH-RRA and B-RRA kappa=0.330, p&lt;0.001; DH-RRA and KF-RRA kappa=0.260, p&lt;0.001; B-RRA and KF-RRA kappa=0.275, p&lt;0.001. Most common last bDMARD choice in RRA patients differed according to the definition: B-RRA mostly adalimumab (30.9%) (p&lt;0.001), KF-RRA tocilizumab (78.1%) (p&lt;0.001), DH-RRA tocilizumab (33.3%) or abatacept (31.6%) (p&lt;0.001) (Figure). Multivariate analysis revealed that, as expected, all definitions were affected by the number of bDMARDs, and DH-RRA also by the disease activity. Mean PDN daily dose was associated with B-RRA; lower BMI with KF-RRA; the start of bDMARD treatment in earlier years with KF-RRA and DH-RRA; and radiographic progression (in the 24 months before the study) with DH-RRA (Table). <h3>Conclusion</h3> RRA was observed in a 20-30% of RA patients, slightly higher compared to previous evidence [1,2]. Characteristics of patients fulfilling different RRA definitions are diverse. Particularly, disease severity (disease activity and structural damage) was not associated with RRA if the definition considers only the exposure to bDMARDs. Given the large time span of the study period, RRA patients were more frequently those who started bDMARDs in earlier years. <h3>References</h3> [1] de Hair MJH, et al. Rheumatology2018;57:1135-1144. [2]. Kearsley-Fleet L, et al. Ann Rheum Dis 2018;77:1405–1412. [3] Buch MH. Ann Rheum Dis 2018;77:966–969. <h3>Disclosure of Interests</h3> None declared