Predictors to Develop Definite Systemic Sclerosis (SSc): Results from an International Multicentre Study on Very Early DiagnOsis of Systemic Sclerosis (VEDOSS)

Silvia Bellando-Randone¹, Gemma Lepri ¹, Dorte Huscher ², Tunde Minier ³, Serena Guiducci ⁴, Cosimo Bruni ¹, Laszlo Czirjak ³, Maurizio Cutolo ⁵, Vanessa Smith ⁶, Jerome Avouac ⁷, Daniel Furst ⁸, Yannick Allanore ⁷, Oliver Distler ⁹ and Marco Matucci-Cerinic ¹⁰, ¹Dept. Experimental and Clinical Medicine, Division of Rheumatology, Azienda Ospedaliera Universitaria Careggi – University of Florence, Florence, Italy, ²Charitè-Universitaetsmedizin Berlin, Berlin, Germany, ³University of Pecs, Pecs, Hungary, ⁴Dept. of Clinical and Experimental Medicine, Section of Rheumatology, University of Florence, Italy, Florence, Italy, ⁵Research Laboratory and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genova, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, Genoa, Italy, ⁶Dept. of Rheumatology, Ghent University Hospital, Ghent, Belgium; Dept. of Internal Medicine, Ghent University, Ghent, Belgium; Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium, Gent, Belgium, ⁷Paris Descartes University, Cochin Hospital, Rheumatology department, Paris, France, ⁸University of California, Los Angeles, CA, ⁹Dept. of Rheumatology, University Hospital Zürich, Zürich, Switzerland, Zürich, Switzerland, ¹⁰University of Florence, Department of Medicine, Florence, Italy, Florence, Italy

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: classification criteria, early diagnosis, Systemic sclerosis, VEDOSS and predictors

Session Information

Date: Wednesday, November 13, 2019

Title: 6W023: Systemic Sclerosis & Related Disorder – Clinical III: Predictors of Outcome (2912–2917)

Session Type: ACR Abstract Session

Session Time: 11:00AM-12:30PM

Background/Purpose: The very early diagnosis of SSc is a challenge today. The aim of the VEDOSS project was to study in an at-risk population, the clinical signs that could predict the progression toward a definite SSc.

Methods: Patients with Raynaud phenomenon (RP), with or without anti-nuclear antibodies (abs) (ANA) were recruited for this longitudinal, observational study. Fulfilling the 2013 classification criteria at baseline was an exclusion criterion. Patients with ANA negative RP were recruited as controls. Patients had an annual assessment according to EUSTAR standards to determine organ involvement and severity. The endpoint was defined as fulfilment of the 2013 SSc classification criteria. The time to fulfilling 2013 classification criteria was evaluated with Kaplan-Meier analysis, and predictors of evolution were determined by univariate and multivariate Cox regression. The study was conducted in accordance with principals of Declaration of Helsinki.

Results: Out of 1,150 recruited patients, 35 were excluded due to non-RP at inclusion and 1.115 patients were analysed. After separating patients with missing ANA status (1), or already fulfilling ACR/EULAR 2013 (240) or ARA 1980 criteria at inclusion (110), the sample was distributed as followed: i) 237 patients (143 with follow up) RP/ANA negative (ANA^–/pRP), ii) 498 patients (401 with follow up) RP/ANA positive (ANA⁺/pRP)): 87 had puffy fingers (PF), 199 had anti-centromere abs (ACA) positive, 45 had anti-topoisomerase-I abs (topo-I) positive and 182 had nailfold videocapillaroscopy (NVC) abnormalities at baseline. Out of 401 ANA⁺/pRP patients, 7.4% within 1 year, 29.3% within 3 and 44.1% within 5 years satisfied the 2013 classification criteria. Out of the 143 ANA^–/pRP patients, none (0%) within 1 year, 4.6% within 3 years, and 4,6% within 5 years satisfied SSc criteria. After adjustment for age, the following baseline parameters were identified as independent predictors for progression into definite SSc by multivariate analysis: PF (OR=3.4 [2.0;5.6]), ACA (OR=2.6 [1.6;4.1]) and Topo-I (OR=3.1 [1.6;5.8]), and NVC abnormalities (OR=1.9 [1.3;2.9]) The presence of PF had a positive predictive value (PPV) of 79% . Combination of PF + specific abs showed 94% PPV and disease specifc abs + NVC abormalities a 82,2% PPV to satisfy ACR/EULAR 2013 criteria within 5 years (Table 1).

Conclusion: The data show that 44% of VEDOSS patients develop, within 5 years of follow up, definite SSc according to classification criteria. At first visit, PF and SSc specific abs were identified as independent parameters predicting the development of definite SSc. These data may allow the risk stratification of patients with very early SSc in clinical practice and clinical studies.

Indipendent predictors for progression into definite SSc

Disclosure: S. Bellando-Randone, None; G. Lepri, None; D. Huscher, None; T. Minier, None; S. Guiducci, None; C. Bruni, Eli Lilly, 5, 8, Actelion, 8; L. Czirjak, None; M. Cutolo, Boehringer, Actelion, Celgene, Bristol-Mayer Squibb, 2; V. Smith, None; J. Avouac, Pfizer, 2, 8; D. Furst, Actelion, 2, 5, Actelion Pharmaceuticals, 2, 5, Amgen, 2, 5, BMS, 2, 5, CME, 5, 8, Corbus, 2, 5, Galapagos, 2, 5, Galapogos Novartis, 5, GlaxoSmithKline, 2, GSK, 2, 5, NIH, 2, Novartis, 2, 5, Pfizer, 2, 5, Roche/Genentech, 2, 5, Sanofi, 2, 5; Y. Allanore, None; O. Distler, A. Menarini, 5, Abbvie, Acceleron, 5, Acceleron Pharma, 5, Actelion, 2, 5, 8, Actelion Pharmaceuticals, 2, 5, 8, 9, Amgen, 5, AnaMar, 2, 5, Bayer, 2, 5, 8, 9, Biogen Idec, 2, 5, Blade Therapeutics, 5, Boehringer Ingelheim, 2, 5, 8, 9, Catenion, 5, 9, ChemomAb, 2, 5, ChemomAB, 5, CSL Behring, 5, Ergonex, 5, espeRare Foundation, 2, 5, Genentech/Roche, 2, 5, GlaxoSmithKline, 5, GSK, 2, 5, Holds Patent mir-29 for the treatment of systemic sclerosis, 9, Inventiva, 2, 5, iQvia, 5, Italfarmaco, 2, 5, Italfarmco, 5, Lilly, 2, 5, med, 5, 8, medac, 5, Medac, 2, 5, MedImmune, 2, 5, Medscape, 5, 8, 9, Menarini, 8, Mepha, 8, Mitsubishi Tanabe, 2, 5, Mitsubishi Tanabe Pharma, 2, 5, MSD, 5, 8, Novartis, 2, 5, 8, 9, Patent, 9, Patent issued, 9, Pfizer, 2, 5, 8, Pharmacyclics, 2, 5, Roche, 5, 8, 9, Sanofi, 2, 5, Sinoxa, 2, 5, Target Bio Science, 5, Target BioScience, 5, UCB, 2, 5, 9, UCB in the area of potential treatments of scleroderma and its complications, 2, 5; M. Matucci-Cerinic, Actelion, 2, 5, 8, Bayer, 5, 8, BMS, 2, 5, Chemomab, 5, J&J, 2, J&J, Janssen, Lilly, MSD, Pfizer, 5, 6, Lilly, 5, Pfizer, 5.

To cite this abstract in AMA style:

Bellando-Randone S, Lepri G, Huscher D, Minier T, Guiducci S, Bruni C, Czirjak L, Cutolo M, Smith V, Avouac J, Furst D, Allanore Y, Distler O, Matucci-Cerinic M. Predictors to Develop Definite Systemic Sclerosis (SSc): Results from an International Multicentre Study on Very Early DiagnOsis of Systemic Sclerosis (VEDOSS) [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/predictors-to-develop-definite-systemic-sclerosis-ssc-results-from-an-international-multicentre-study-on-very-early-diagnosis-of-systemic-sclerosis-vedoss/. Accessed .

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