POS0813 PREDICTORS OF RESPONSE TO bDMARDs AND tsDMARDs THERAPY: THE ROLE OF MUSCULOSKELETAL ULTRASOUND AND POTENTIAL NEW BIOMARKERS
Authors: G. Cozzi, M. Lorenzin, F. Oliviero, L. Scagnellato, A. Damasco, C. Cosma, A. Doria, D. Basso, R. Ramonda
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The heterogeneity of clinical manifestations of psoriatic arthritis (PsA) makes it challenging to validate clinical, biomarker, and instrumental predictors of therapy response. Ultrasound (US) is a validated diagnostic tool that integrates the clinical examination of PsA patients. <h3>Objectives:</h3> The aim of this pilot study was to identify early US and biomarker predictors of the retention rate of therapy with biologic and targeted synthetic disease-modifying antirheumatic drugs (bDMRDs and tsDMARDs). The secondary endpoint was to identify differences in sonographic scores among patients treated with different therapeutic classes. <h3>Methods:</h3> In this prospective observational study, patients with peripheral PsA, either treatment-naïve or with an inadequate response to bDMARDs, were enrolled. At baseline, they had to present clinically active arthritis and/or enthesitis/tendonitis, for which bDMARD/tsDMARD therapy was indicated according to the clinician. Clinical and US assessments were conducted at baseline (t0), 1 month (t1), 3 months (t3), and 6 months (t6) from the start of therapy. Additionally, at t0 and t6, serological tests were performed, including CRP, ESR, IL-1β, IL-6, TNF, BMP-2, IgA, c3, and c4. US evaluations were performed for the joints/entheses included in the PsASon-Score13 (US composite scores for the assessment of inflammatory and structural pathologies in Psoriatic Arthritis) and, if not already included in the aforementioned score, for the joint/enthesis/tendon or the two most clinically affected joints/entheses/tendons (MIJET and 2MIJET, respectively). Patients were defined as clinical Responders (cResponders) if they continued ongoing therapy at t6 according to clinical judgment. Conversely, they were defined as non-cResponders if therapy discontinuation was required due to failure at t6 according to clinical evaluation. The main endpoints were the ultrasound changes in synovitis/enthesitis/tenosynovitis of MIJET, 2MIJET and the GUIS (Global US Inflammation Subscore) derived from PsASon-13. <h3>Results:</h3> A total of 29 consecutive patients were enrolled (9 naive for bDMARDs). Among these, 22 were cResponders and 7 were non-cResponders at the t6 evaluation. The difference in the mean variation of GUIS in the Δt6-0 interval showed a significant difference in cResponders compared to non-cResponders (-5,136 vs 1,0; p=0,023), but was not significant in Δt1-0 and Δt3-0. The comparison between the mean variations of MIJET and 2MIJET in cResponders compared to non-cResponders showed a statistically significant difference in Δt3-0 and Δt6-0 (MIJET: Δt3-0: -1,727 vs 0,0; p=0,00236; Δt6-0: -1,864 vs 0,1429; p=0,0055; 2MIJET: Δt3-0: -3,227 vs -0,7143; p=0,0497; Δt6-0: -3,409 vs 0,1429; p=0,0030), and was not significant in Δt1-0 (<i>Figure 1</i>). The ultrasound response of MIJET and 2MIJET was faster in cResponder patients treated with JAKi in Δt1-0 compared to those treated with TNFi(MIJET: -2,6 vs -0,444, p=0,0491; 2MIJET: -4,2 vs -1,111, p=0,0333) and IL-17/12-23i(MIJET: -2,6 vs -0,1, p=0,0194; 2MIJET: -4,2 vs -0,3, p=0,0021) (<i>Figure 2</i>). The variation in IgA values was higher in non-cResponder patients compared to cResponders in Δt6-0 (-0,8600 vs -0,1529, p=0,0210). No other significant variations were found in other serological tests. <h3>Conclusion:</h3> This study highlights how US can be an early predictor of therapy response. Given the impracticality of evaluating the numerous joint sites included in the main composite US assessment scores, the results of our study indicate that ultrasound imaging of the clinically most involved joint sites can be an equally valid alternative as a predictor of therapy retention rate at 6 months. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>