PO:31:172 | Age and timing of onset of Raynaud's phenomenon and first non-Raynaud sign/symptom as prognostic factors in systemic sclerosis: a retrospective analysis from the systemic sclerosis progression investigation registry of the Italian Society for Rheumatology

Silvia Peretti¹, Cosimo Bruni², Silvia Laura Bosello³, Fabio Cacciapaglia^4-5, Corrado Campochiaro^6-7, Veronica Codullo⁸, Lorenzo Dagna^6-7, Rossella De Angelis⁹, Giacomo De Luca^6-7, Dilia Giuggioli¹⁰, Serena Guiducci¹, Florenzo Iannone⁴, Francesca Ingegnoli¹¹, Valeria Riccieri¹², Marco Matucci Cerinic^6-7, Clodoveo Ferri^10-13, Silvia Bellando Randone¹. | ¹Division of Rheumatology, Scleroderma Unit, Department of Experimental and Clinical Medicine, University of Florence, AO, Firenze, Italy; ²Division of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; ³Rheumatology Division, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli- IRCCS, Roma, Italy; ⁴Rheumatology Unit, Department of Precision and Regenerative Medicine-Ionian Area, University of Bari Aldo Moro, Bari, Italy; ⁵Reumatology Service, Internal Medicine Unit F.Miulli General Hospital, Acquaviva delle Fonti -Department of Medicine a, Bari, Italy; ⁶Unit of Immunology, Rheumatology, Allergy and Rare Diseases UnIRAR, Inflammation, Fibrosis and Ageing initiative INFL, Milano, Italy; ⁷Vita-Salute San Raffaele University, Milano, Italy; ⁸Department of Internal Medicine and Therapeutics, Università di Pavia, Italy; Division of Rheumatology, Fondazione IRCCS, Pavia, Italy; ⁹Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy; ¹⁰Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena, Italy; ¹¹Division of Clinical Rheumatology, ASST Pini, Dept. of Clinical Sciences and Community Health, Research Center for Adul, Milano, Italy; ¹²Department of Rheumatology, Sapienza University of Rome, Roma, Italy; ¹³Rheumatology Clinic Madonna dello Scoglio Crotonei, Crotone, Italy.

Background. To investigate whether age and timing of Raynaud’s phenomenon (RP) and non-Raynaud’s phenomenon (NRP) onset influence systemic sclerosis (SSc) endotype and prognosis.

Materials and Methods. We performed a cross-sectional study including patients from the SPRING Registry, fulfilling the SSc 2013 ACR/EULAR criteria(1). Patients were categorized into 4 groups based on age at RP (age-RP) and age at NRP (age-NRP) onset, according to quartiles’ distribution. Additionally, patients were divided into 3 groups based on RP onset timing:1) RP >1 year after NRP onset (NRP group); 2) RP and NRP within the same year (Simultaneous group, SG), 3) RP >1 year before NRP onset (RP group). Comparisons were performed using Chi-square, ANOVA, logistic, linear, and multinomial regression models. Kaplan-Meier and Cox regression were used to evaluate survival.

Results. 1748 SSc patients were eligible for the study: 682 (39%) in the RP group, 1026 (58.8%) in the SG, and 39 (2.2%) in the NRP group. The RP group had a higher prevalence of anti-centromere antibodies (ACA, 41.5%), whereas the SG presented more anti-topoisomerase I antibodies (ATA, 41.1%), diffuse cutaneous SSc (dcSSc, 25.2%), and higher modified Rodnan Skin Score (mRSS) (5, IQR 2–10). The NRP group showed more pulmonary arterial hypertension (PAH, 15.8%) and less dcSSc (5.1%), without a distinct autoantibody profile. Dividing patients by age-RP quartiles, those in the youngest group (18–34 years) had more ATA (42.2%), dcSSc (23.4%), digital ulcers (DU, 29.2%) and digital pitting scars (DPS, 58.2%) while the oldest group (>56 years) had more cardiopulmonary involvement (35.3%) with higher systolic pulmonary arterial pressure (sPAP, 25±18 mmHg). Similar trends emerged with age-NRP stratification. Logistic regression showed that SG was associated with higher dcSSc prevalence vs RP (OR 1.491, 95% CI 1.032–2.154), independently of ATA and sex. Earlier age-RP predicted lower sPAP (beta -0.149, 95%CI: -0,297, -0,001) and mRSS (beta -0.053, 95%CI -0,094, -0,011). Among 943 patients with follow-up (median 24 months), estimated survival was comparable (RP 97%, NRP 95%, SG 94%). However, on multivariable regression, the SG had a significant higher mortality compared to the RP group, independently from patient’s age, sex, disease activity and Charlson Comorbidity Index (HR 1.975; 95%CI 1.002-3.893). Moreover, multinomial regression showed that female sex (OR 2.445, 95%CI 1.052-5.681) and ACA positivity (OR 2.004; 95%CI 1.550–2.597) were associated with the RP group. Older age-RP increased the likelihood of belonging to the NRP (OR 1.067; CI 1.042–1.092) or SG (OR 1.048; 95%CI 1.041–1.056) groups. ATA (OR 1.671; 95%CI 1.295–2.157;) and Anti-RNA Polymerase III Antibody (OR 4.002; 95%CI 1.151–13.914) positivity were linked to higher odds of inclusion in the SG.

Conclusions. Timing of RP and NRP onset influences SSc endotype and prognosis. Simultaneous onset is linked to more severe disease and worse survival, highlighting the potential role in patient stratification.