PO:01:003 | Sex-based differences in 2 years treatment outcomes with b/ts-DMARDs in psoriatic arthritis: from real-world evidence to predictive modeling from the Gruppo Italiano Studio Early Arthritis (GISEA) prospective registry

Simone Perniola¹, Florenzo Iannone¹, Francesco Paolo Cantatore², Angelo Semeraro³, Leonardo Santo⁴, Roberto Gorla⁵, Alberto Cauli⁶, Roberto Felice Caporali⁷, Bruno Frediani⁸, Rosario Foti⁹, Fabrizio Conti¹⁰, Marco Sebastiani¹¹, Maria Sole Chimenti¹², Roberta Ramonda¹³, Fabiola Atzeni¹⁴, Maurizio Rossini¹⁵, Serena Bugatti¹⁶, Serena Guiducci¹⁷, Giovanni Lapadula¹, Gianfranco Ferraccioli¹⁸, Francesca Romana Spinelli¹⁰, Elisa Gremese¹⁹. | ¹Rheumatology Unit, DiMePReJ, University of Bari, Bari; ²Rheumatology Unit, Department of Medical and Surgical Sciences, Azienda Ospedaliero-Universitaria Policlinico Riuniti, Foggia; ³Rheumatology Unit, Martina Franca Hospital; ⁴Rheumatology Unit, ASL BT, P.O. Barletta; ⁵Rheumatology and Clinical Immunology Unit, ASST Spedali Civili of Brescia; ⁶Rheumatology Unit, Department of Medical Science and Public Health, University of Cagliari, Monserrato (CA); ⁷Rheumatology Unit, Dipartimento di Reumatologia e Scienze Mediche, ASST PINI-CTO, University of Milano, Milano; ⁸Rheumatology Unit, Azienda Ospedaliero Universitaria Senese, Siena; ⁹Rheumatology Unit, A.O.U. Policlinico S. Marco, Catania; ¹⁰Rheumatology Unit, Department of Clinical Internal, Anesthesiologic and CV Sciences, Sapienza University of Rome, Roma; ¹¹Rheumatology Unit, AUSL Piacenza, University of Parma, Parma; ¹²Rheumatology, Department of Systems Medicine, University of Rome Tor Vergata, Roma; ¹³Rheumatology Unit, DIMED, University of Padua, Padova; ¹⁴Rheumatology Unit, Department of Experimental and Internal Medicine, University of Messina, Messina; ¹⁵Rheumatology Unit, Department of Medicine, University of Verona, Verona; ¹⁶Division of Rheumatology, Dept. of Internal Medicine and Therapy, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Pavia; ¹⁷Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Firenze, Firenze; ¹⁸Department of Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Gemelli IRCCS, Roma; ¹⁹Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Humanitas University, Rozzano (MI), Italy

Background. Psoriatic arthritis (PsA) presents several evidence of sex-related disparities, highlighting critical gaps in our understanding and management of PsA. This study aimed to evaluate b/ts-DMARDs effectiveness, drug survival and clinical response predictors in PsA patients, related to biological sex.

Patients and Methods. PsA patients starting a b-/ts-DMARDs between January 2016 and December 2023 were included in this multicentre real-world observational study based on the Italian GISEA prospective registry. Demographic, laboratory and clinical data were collected at baseline and at four-months interval thereafter.Logistic regression was used to investigate the association between selected variables and MDA achievement at T4, reporting as adjusted odds ratio (adjOR) with 95% confidence interval (CI), adjusting for age, BMI, csDMARDs and steroid user and baseline DAPSA score.

Results. A total of 4197 PsA patients were enrolled, comprising 1714 males (mPsA) and 2483 females (fPsA). Comparing to fPsA patients, mPsA were characterized by a higher BMI (p=0.01), longer disease duration (p=0.0001) and more frequent psoriasis (p<0.0001).Moreover, mPsA compared to fPsA exhibited a higher prevalence of the oligoarticular pattern (p=0.003), higher CRP levels (p<0.0001), and more presence of erosion (p=0.045), but lower DAPSA score (p<0.0001). Significant differences in clinical improvement were observed at each time point between mPsA and fPsA in terms of DAPSA remission and MDA achievement. Furthermore, female gender had a negative impact on retention rates of b/ts-DMARD therapy only at first- or second-line compared to male gender (p<0.0001 and p=0.023, respectively). PsA patients who achieved MDA at T4 were more likely to be male (p<0.0001), have an oligoarticular pattern (p<0.0001), lack enthesitis involvement (p<0.0001), be free of fibromyalgia comorbidity (p<0.0001) and be b-/ts-DMARDs naïve (p=0.001). Based on these findings, the five features were considered in a predictive model of MDA achievement at T4 with adjOR 9.826 (95% CI 3.215-30.035). Finally, fPsA with fibromyalgia (fibro/fPsA; n: 363) compared to fPsA without fibromyalgia (not-fibro/fPsA; n: 1132) were characterized by lower psoriasis involvement (p=0.015), associated to lower PASI (p=0.005), higher enthesitis involvement (p<0.0001), associated to higher LEI (p<0.0001), higher axial involvement (p<0.0001) and higher DAPSA (p=0.001). Furthermore, not-fibro/fPsA patients demonstrated significantly better clinical response compared to fibro/fPsA in terms of DAPSA remission and MDA achievement.

Conclusions. This large, multicentre real-world observational study reveals striking significant sex-related differences in clinical features, disease activity and treatment response among PsA treated patients. Notably, mPsA patients demonstrated better outcomes at every time points of follow-up compared to fPsA. The study also identified key predictive factors, including biological sex, for early MDA achievement, highlighting the importance of integrating sex-specific approaches into PsA management.