ABS0904 CLINICAL AND ULTRASOUND PHENOTYPING OF D2T SpA PATIENTS: A MONOCENTRIC COHORT EXPERIENCE

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Background: Patients with seronegative spondyloarthritis (SpA) may display failure to multiple lines of treatment with targeted synthetic (ts) or biologic (b) agents (DMARDs), and persistent clinical and/or ultrasound (US) disease activity. No clear definition of difficult-to-treat (D2T) SpA was released so far [1], requiring further investigation. Objectives: To characterize clinical and US features that may help the recognition of D2T-SpA patients. Methods: Patients with diagnosis of SpA followed up from January 2020 to September 2024 at our clinic were enrolled in this retrospective study. D2T SpA was defined as persistent symptoms and/or signs of activity after failure of ≥2 lines of b/tsDMARDs. Demographic and clinical data were recorded at baseline and at different timepoints. We defined as index US the one performed in patients prescribed with no more than two subsequent lines of b/tsDMARDs and not yet defined as D2T. The following joint sites were evaluated by US: wrists, metacarpophalangeal joints (MCP), proximal interphalangeal joints (PIP), knees and ankles. All US assessments were performed by expert rheumatologists from our center following a standardized scanning technique [2], using an Esaote MyLabX8 ultrasound machine with a high-resolution 15-24 MHz linear probe. All areas were evaluated for synovitis, erosions and tenosynovitis, according to OMERACT definitions of pathology [3]. US and clinical parameters were analyzed through parametric or non-parametric tests for continuous and categorical variables. Predictors of D2T phenotype were assessed through logistic regression. Results: One hundred and seventy-nine patients were included in the study with a mean follow-up (± standard deviation, SD) of 11.33 ± 7.31 years (Table 1). Considering the whole cohort, 90 (50.2%) patients were classified as D2T. Among them, 91.1% were diagnosed with psoriatic arthritis (PSA), 6.7% with ankylosing spondylitis (AS) and 2.2% with non-radiographic axial spondyloarthritis (nr-axSpA). Conclusion: Among D2T SpA patients, the majority presented with PSA and nail involvement. D2T-SpA/PSA patients exhibit distinct clinical and predating US features (higher prevalence of tenosynovitis of the wrist extensors and IFP synovitis) which may harbor a difficult phenotype. These findings suggest the importance of integrating clinical and US parameters to better identify and manage D2T-SpA patients. REFERENCES: [1] Singla S et al. Difficult-to-treat psoriatic arthritis (D2TPsA): a scoping literature review informing a GRAPPA research project. RMD Open 2024;10:e003809. [2] Möller I et al. The 2017 EULAR standardised procedures for ultrasound imaging in rheumatology. Ann Rheum Dis. 2017 Dec;76(12):1974-1979. [3] Bruyn GA et al. OMERACT Definitions for Ultrasonographic Pathologies and Elementary Lesions of Rheumatic Disorders 15 Years On. J Rheumatol. 2019 Oct;46(10):1388-1393. Table 1Baseline features SpA cohortVariableD2TSpA n=90Non D2TSpA n=89p-valueGender (% of F)51.248.80.751Age at diagnosis46.7 ±12.150.9± 11.50.018Lag time from symptoms onset to diagnosis (years)6.4± 173.81±7.150.093BMI30.4± 21.229.9 ±27.70.148Comorbidities* (%) y/n52.447.60.415Fibromyalgia (%)60.439.30.061Smoking (%)54.345.70.600TJ8.78 (8.85)5.97 (6.00)<0.001SJ0.88 (1.46)0.33 (0.85)<0.001Time to first biologic (years)3.76± 5.492.53 ±4.450.456Used drug class % (b/ts)Anti-TNF63.836.2<0.001Anti-IL1789.510.5<0.001Anti-IL(12)2310000.059JAKi91.78.3<0.001*Cardiovascular accidents, diabetes, neoplasms, hypertension, renal failureBMI, body mass index; FM, fibromyalgia; TJ tender joints; SJ swollen joints; TNF tumor necrosis factor; JAKi, Jak InhibitorsPSA was the most frequent SpA subtype in D2TSpA (54.3% vs 45.7 , p=0.035 ) whereas nr-axSpA was more frequently observed in the non D2TSpA group (80% vs 20%, p=0.048 ).Relative to non-D2TSpA, D2TSpA patients were younger, displayed a predominant peripheral disease pattern (54.3% vs 45.7%, p=0.014 ) and a more frequent nail involvement (95% vs 6.5%, p=0.009 ). A higher tender joint ( TJ ) count and swollen joint ( SJ ) count was observed in the D2TSpA group (respectively 8.78 ± 8.85 vs 5.97 ± 6.00 and 0.88 ± 1.46 vs 0.33 ± 0.85, p<0.001 for both ). Nail involvement (OR 12.77 95% CI 1.29-126.32; p=0.029 ) and PSA diagnosis (OR 15.48, 95% CI 2.49-96.12; p=0.003 ) were independent baseline clinical predictors of D2TSpA. Given the prominent proportion of PsA patients in the SpA cohort, we conducted a sub-analysis on 153 patients with PSA. Eighty-two (53.6%) were D2TPSA. Consistently with the whole cohort, D2TPSA patients displayed a younger age at diagnosis (47.5 ± 11.3 vs 53.2 ± 10.1, p<0.001 ) and widespread nail involvement (94.7% vs 5.3%, p=0.035 ). We gathered index US data in 129 PSA patients (46.5% D2T-PSA and 53.5% non D2T-PSA). Tenosynovitis of the wrist extensors was present in those who would become D2T (75% vs 25%, p=0.096 ), and particularly right wrist extensors synovitis was significantly associated with D2T-PSA (85.7% vs 14.3%, p=0.038 ). IFP synovitis was present in 75% of patients with D2T-PSA vs 25% of non D2T-PSA ( p=0.096 ). Regarding predictors of D2T phenotype (Table 2), presence of nail involvement emerged as an independent predictor in the whole cohort as well as in the PSA subgroup. Wrist extensor tenosynovitis approached significance as an independent baseline US predictor of D2T-PSA (HR 3.12, 95% CI 0.57-16.8, p=0.080 ). Table 2Independent predictors of D2T-SpA and PSAVariableOR95%CIp-valueSpA (whole cohort)Nail involvement12.771.29-126.320.029PSA15.482.49-96.120.003PSANail involvement8.951.05-76.280.045Smoke (ever)5.821.08-31.350.040USWrist extensor tenosynovitis3.120.57-16.80.080SpA, seronegative spondyloarthritis; PSA, psoriatic arthritis; US, ultrasound; OR, odds ratio Acknowledgements: NIL . Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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