Blaz Burja1, Marouane Boubaya2, Patricia Carreira3, Christina Bergmann4, Lidia P Ananieva5, Gabriela Riemekasten6, Okada Masado7, Jeska de Vries-Bouwstra8, Edoardo Rosato9, Marie-Elise Truchetet10, Nicoletta Del Papa11, Antonella Marcoccia12, FABIOLA ATZENI13, Tim Schmeiser14, Madelon Vonk15, Francesco Del Galdo16, Oliver Distler17 and Muriel Elhai18, 1Center of Experimental Rheumatology, Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, 2Department of Clinical Research, CHU Avicenne, APHP, Bobigny, France, 3Hospital Universitario 12 de Octubre, Madrid, Spain, 4Department Internal Medicine, University Hospital Erlangen, Germany, Erlangen, Germany, 5V.A. Nasonova Research Institute Of Rheumatology Russian Federation, Moscow, Russia, 6University Clinic Schleswit-Holstein (UKSH), Lübeck, Germany, 7St.Luke's International Hospital Immuno-Rheumatology Center, Tokyo, Japan, 8Leiden University Medical Center, Leiden, Netherlands, 9Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy, 10Bordeaux University Hospital, Bordeaux, France, 11Scleroderma Clinic, UOC Reumatologia Clinica, ASST G. Pini-CTO, Milano, Italy, 12Centro Di Riferimento Interdisciplinare Per La Sclerosi Sistemica, Rome, Italy, 13Rheumatology Unit, Univerity of Messina, Messina, Italy, 14Krankenhaus St. Josef, Wuppertal-Elberfeld, Germany, 15Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, 16University of Leeds - Leeds Institute of Rheumatic and Muskuloskeletal Medicine, Leeds, United Kingdom, 17Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland, 18Department of Rheumatology, University Hospital Zurich, University of Zurich, Schlieren, Switzerland
Background/Purpose: Despite the progress in understanding the patient heterogeneity in systemic sclerosis (SSc) based on SSc-specific antibodies, better risk stratification is needed. SSc non-specific antibodies might represent surrogate markers to improve the stratification of SSc patients. Here, we aim 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 ACR 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 using t-test and chi-squared according to the distribution of the variable. The progression of lung fibrosis was defined (i) in patients with lung fibrosis (FVC%decline from baseline of ≥ 10% or an FVC%decline of 5-9% in association with aDLCO% decline of ≥15%)or (ii) by a decline of FVC >5% in patients with lung fibrosisor (iii) by the development of lung fibrosis de novo (on HRCT scan). Prognostic factors for lung fibrosis progression and death during the 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 more frequently observed among Asians and Africans and less prevalent in Caucasians (Table 1). 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), PAPs >45 mmHg on echocardiography (9.2% vs. 6.5%, p=0.058) and lung fibrosis on HRCT (56.2% vs 47.8%, p=0.001). Specifically, the percentage predicted of DLCO in patients with lung fibrosis was significantly lower in patients with anti-SSA antibodies (59.0±18.6% vs. 61.9±20.2, p=0.041). Over a median follow-up of 2.4 years [95CI: 2.2-2.9], anti-SSA antibodies did not predict lung fibrosis progression ((i) HR: 1.03 [0.8-1.33], (ii) HR: 1.05 [0.83-1.31] and (iii) HR: 0.98 [0.72-1.32] or death (HR: 1.27 [0.8-2]).
Conclusion: In the large EUSTAR cohort, anti-SSA antibodies are detected in 15% of SSc-patients and are associated with more severe lung involvement. These data support the inclusion of anti-SSA antibodies in clinical practice for better SSc-patient risk stratification.
Table1: Comparison of SSc-patients with and without anti-Ro/SSA antibodies
B. Burja: None; M. Boubaya: None; P. Carreira: None; C. Bergmann: Boehringer-Ingelheim, 2, 5, Janssen, 2; L. Ananieva: None; G. Riemekasten: None; O. Masado: None; J. de Vries-Bouwstra: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, galapagos, 5, Janssen, 2, 6, Janssen-Cilag, 5, Roche, 5; E. Rosato: None; M. Truchetet: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, Gilead, 5, 6, Merck/MSD, 6, UCB, 6, 12, support for conferences; N. Del Papa: None; A. Marcoccia: None; F. ATZENI: None; T. Schmeiser: None; M. Vonk: Boehringer Ingelheim, 5, 6, Corbus, 1, EUSTAR, 4, Ferrer, 5, Galapagos, 5, Janssen, 5, 6, MSD, 6, Systemic Sclerosis ERN ReCONNET, 4; F. Del Galdo: AbbVie/Abbott, 5, arxx, 2, AstraZeneca, 2, 5, Boehringer-Ingelheim, 2, 5, capella, 2, Chemomab, 2, GlaxoSmithKlein(GSK), 2, Janssen, 2, Mitsubishi-Tanabe, 2, 5; O. Distler: 4P-Pharma, 2, 5, 6, AbbVie, 2, 5, 6, Acceleron, 2, 5, 6, Alcimed, 2, 5, 6, Altavant Sciences, 2, 5, 6, Amgen, 2, 5, 6, AnaMar, 2, 5, 6, Arxx, 2, 5, 6, AstraZeneca, 2, 5, 6, Bayer, 2, 5, 6, Blade Therapeutics, 2, 5, 6, Boehringer Ingelheim, 2, 5, 6, Citus AG, 12, Co-Founder, Corbus Pharmaceuticals, 2, 5, 6, CSL Behring, 2, 5, 6, Galapagos, 2, 5, 6, Galderma, 2, 5, 6, Glenmark, 2, 5, 6, Gossamer, 2, 5, 6, Horizon Therapeutics, 2, 5, 6, Janssen, 2, 5, 6, Kymera, 2, 5, 6, Lupin, 2, 5, 6, Medscape, 2, 5, 6, Miltenyi Biotec, 2, 5, 6, Mitsubishi Tanabe, 2, 5, 6, MSD, 2, 5, 6, Novartis, 2, 5, 6, Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143), 10, Prometheus Biosciences, 2, 5, 6, Redx Pharma, 2, 5, 6, Roivant, 2, 5, 6, Topadur, 2, 5, 6; M. Elhai: AstraZeneca, 12, Congress support, Janssen, 12, Congress support.