PO:32:182 | Disease characteristics of anti-centromere positive systemic sclerosis patients and risk factors for organ involvement: data from the EUSTAR cohort

Corrado Campochiaro¹, Jelena Colic², Del Papa Nicoletta³, Oliver Distler⁴, Serena Guiducci⁵, Florenzo Iannone⁶, David Launay⁷, Yair Levy⁸, Britta Maurer⁹, Arsene Mekinian¹⁰, Predrag Ostojic², Gabriela Riemekasten¹¹, Petros Sfikakis¹², Bojana Stamenkov¹³, Ulrich Walker¹⁴, Marie Elise Truchetet¹⁵, Madelon Vonk¹⁶, Francesco Del Galdo¹⁷, Giacomo De Luca¹, Lorenzo Dagna¹, Marco Matucci Cerinic¹, Yannick Allanore¹⁸ | ¹IRCCS San Raffaele Hospital; Vita Salute San Raffaele University Milan, Italy; ²University of Belgrade Belgrade, Serbia; ³UOC Reumatologia Clinica, ASST G. Pini CTO Milan, Italy; ⁴University Hospital Zurich Zurich, Switzerland; ⁵Department of Rheumatology, University of Florence Florence, Italy; ⁶Rheumatology Unit Bari, Italy; ⁷CHU Lille Lille, France; ⁸Department of Medicine Kfar Saba, Israel; ⁹Department for BioMedical Research, University of Bern Bern, Switzerland; ¹⁰Service de medecine interne Paris, France; ¹¹Department of Rheumatology University of Lubeck Lubeck Germany; ¹²National and Kapodistrian University of Athens Athens, Greece; ¹³University School of Medicine, Nis Nis, Serbia; ¹⁴University Hospital Basel, Basel Basel, Switzerland; ¹⁵Bordeaux Hospital and University Bordeaux, France; ¹⁶Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; ¹⁷Leeds Institute of Rheumatic and Muskuloskeletal Medicine Leeds, United Kingdom; ¹⁸Cochin Hospital Paris, France

Background and Objectives. Although anti-centromere autoantibodies(ACA) are the most prevalent autoantibodies in systemic sclerosis(SSc), the risk of organ involvement in these patients remains poorly defined. We aimed to assess the prevalence of organ involvement among ACA+SSc patients and to identify risk factors associated with disease-related involvement

Methods. SSc patients from the EUSTAR database with known ACA-positive status, were included. Patients’ data were analyzed at their first inclusion in database(“whole cohort”). Those with available information about disease duration, were then segregated into 4 different cohorts based on their disease duration: T1(0-1 year); T2(2-5 years); T3(6-10 years) and T4(>10 years). The following organ involvements were explored: ILD(based on HRCT); PH(echo sPAP>=45mmHg as a proxy); heart involvement; scleroderma renal crisis(SRC); gastrointestinal(GIT), musculoskeletal involvement(MSK) and digital ulcers(DUs). The prevalence of organ involvements in the whole cohort and the 4 derived cohorts was calculated. Multivariable logistic regression models were built to identify risk factors for specific damage in the entire cohort and in those belonging to T1. The final risk model was based on 3 different clusters: cluster 1(demographic and lifestyle), cluster 2(variables already identified in the literature) and cluster 3 (relevant variables based on expert opinion), using stepwise selection based on the Akaike Information Criterion and ROC and AUC analysis.

Results. 7723(39.6%) ACA-positive SSc patients were identified. Demographics are shown in Figure 1A. GIT involvement was the most common(67.6%) followed by DU(31.2%) and MSK(29.9%), see Figure 1A. Disease duration was available for 6286(81%) patients. After segregating patients, 1150(18.3%) patients belonged to T1, 1871(29.8%) to T2, 1392(22.1%) to T3 and 1873(29.8%) to T4. In these 4 cohorts a significant increase in the prevalence of organ involvements from T1 to T4 was observed(p<0.05 for all comparisons), reaching 2-3 times higher for the majority of organ damage in T4 compared to T1, see Figure 1B. At multivariable logistic regression analyses in the whole cohort(Figure 2A), the strongest predictors for organ involvement were: age of onset >50 years for echoPH and heart involvement, male gender and %pFVC<80 for ILD, telangiectasias for PH, late capillaroscopy pattern and male gender for DU and raised CRP for ILD, PH and heart involvement. After restricting the analysis on T1(Figure 2B) we confirmed that age >50 years is an independent risk factor for heart involvement, male gender for ILD and DU, %pFVC<80 for ILD and raised CRP for ILD and heart involvement.

Conclusions. ACA-positive SSc patients experience disease progression over time. We identified risk factors for different organ involvements in the whole cohort and in early patients. Future analyses will confirm whether these risk factors will also apply to patients with longer disease duration to validate the 'red flags' that might guide clinical practice and participation of specific individuals in future clinical trials.