Background: Despite the progress in explaining the clinical heterogeneity in systemic sclerosis (SSc) based on SSc-specific antibodies, better understanding of additional risk factors is needed. SSc non-specific antibodies might represent additional markers to improve the stratification of SSc patients.

Objectives: We aimed to evaluate the prevalence of anti-Ro/SSA antibodies in the largest available cohort of established SSc patients and study their association with disease phenotype and clinical outcomes, focusing on lung involvement.

Methods: Patients from the EUSTAR database fulfilling the 2013 classification criteria for SSc, with available data on anti-Ro/SSA antibodies, were included. Clinical characteristics of patients with or without anti-Ro/SSA antibodies were compared at baseline. Patients who had at least one follow-up visit were included in the longitudinal analysis. The presence of lung fibrosis on HRCT was assessed over the follow-up. Multivariable logistic regression models were built to identify factors associated with lung fibrosis. The association between anti-Ro/SSA antibodies and FVC as well as DLCO in patients with lung fibrosis was assessed using linear regression. The progression of lung fibrosis was defined by FVC% decline from baseline of ≥ 10% or a FVC% decline of 5-9% in association with a DLco% decline of ≥15% or by a decline of FVC >5% in patients with lung fibrosis or by the development of lung fibrosis de novo. Prognostic factors for progression of lung fibrosis and death during follow-up were tested by multivariate Cox proportional hazards regression. Covariates were selected according to literature evidence. Multiple imputation was used to impute missing data in these models.

Results: Among the 4’421 patients fulfilling the inclusion criteria, 661 (15.2%) had positive anti-Ro/SSA antibodies. Anti-Ro/SSA antibodies were positively associated (p<0.001) with anti-SSB, anti-U1RNP antibodies, and rheumatoid factor. Patients with anti-Ro/SSA antibodies more frequently presented with muscular involvement (18% vs 12.5%, p<0.001), and lung fibrosis (56.2% vs 47.8%, p=0.001) at baseline (Table 1). Over a median follow-up of 2.7 years (95% CI: 2.6–2.9), 14’066 visits were recorded. In multivariable logistic regression, anti-SSA independently predicted the presence of lung fibrosis in at least one follow up visit (OR 1.24 [1.07-1.44], p=0.006) (Figure 1) and lower DLCO in patients with lung fibrosis (regression coefficient: -1.93 [-3.83-0.02], p=0.049). Anti-SSA antibodies had a trend to predict lower FVC in patients with lung fibrosis (p=0.082). Anti-SSA antibodies did not predict the progression of lung fibrosis or death during the follow-up.

Conclusion: In the large EUSTAR cohort, anti-SSA antibodies are detected in 15% of SSc-patients and represent an independent risk factor for the presence of lung fibrosis. They are also predictive of more severe lung involvement. These data support the inclusion of anti-SSA antibodies in routine clinical practice to improve the risk-stratification of SSc patients.

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Figure 1.

Predictive factors for presence of lung fibrosis at least at one visit over the follow-up. Marked in red are factors significantly predictive for lung fibrosis.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Blaž Burja: None declared, Marouane Boubaya: None declared, Cosimo Bruni Boehringer Ingelheim, Foundation for Research in Rheumatology (FOREUM), Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Foundation for research in Rheumatology (FOREUM), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), Novartis Foundation for Bio-medical Research, EMDO Foundation, Patricia Carreira Janssen, Lilly, VivaCell, Emerald Health Pharmaceuticals, Gesynta Pharma, Boehringer Ingelheim, Abbvie, Sanofi Genzyme, Mitsubishi Tanabe, Christina Bergmann: None declared, Lidia P. Ananyeva: None declared, Gabriela Riemekasten: None declared, Okada Masado: None declared, Jeska K. de Vries-Bouwstra Dutch Society (payments made to institution), Boehringer Ingelheim (payments made to institution), Janssen-Cilag (payments made to institution)., Boehringer Ingelheim, Jansen-Cilag and Abbvie, ReumaNederland (Dutch patient Society for Rheumatology), Nationale Vereniging voor mensen met lupus, APS, sclerodermie en MCTD (Dutch patient society), ARCH (Autoimmune Research and Collaboration Hub; Dutch interdisciplinary society for patients and caregivers), Janssen-Cilag, and Boehringer Ingelheim, Edoardo Rosato: None declared, Marie-Elise Truchetet: None declared, Nicoletta Del Papa: None declared, Antonella Marcoccia: None declared, Fabiola Atzeni: None declared, Tim Schmeiser: None declared, Madelon Vonk: None declared, Francesco Del Galdo: None declared, Oliver Distler 4P-Pharma, Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Argenx, Arxx, AstraZeneca, Blade, Boehringer Ingelheim, Citus AG, Corbus, CSL Behring, Enzyvant (Sumitomo), Galderma, Galapagos, Glenmark, Gossamer, Kymera, Lupin, Medscape, Merck, Miltenyi Biotec, Mitsubishi Tanabe; Novartis, Orion, Prometheus, Redxpharna, Roivant, Topadur and UCB, Kymera, Mitsubishi Tanabe, Muriel Elhai: None declared.