FRI0315 SERUM INTERFERON SCORE PREDICTS CLINICAL OUTCOME AT 12 MONTHS IN DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS AS MEASURED BY GLOBAL RANKED COMPOSITE SCORE (GRCS) AND COMPOSITE RESPONSE INDEX IN SSC(CRISS)
Authors: Antonio Carriero, Giuseppina Abignano, Michelle Hutchinson, Karri Ballard, Sookhoe Eng, Paul Emery, Maya Buch, Francesco Del Galdo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic sclerosis (SSc) is a disease orphan of effective disease modifying agents. The diffuse cutaneous subset (dcSSc) is targeted in most clinical trials. Nevertheless, the high variability in clinical outcome at 12 months is limiting effective RCTs design and interpretation. The Global Ranked Composite Score (GRCS) and the Composite Response Index in SSc (CRISS) are the most recent attempts to capture overall response to treatment in dcSSc [1, 2]. Activation of interferon type 1 (IFN) pathway is associated with severe clinical manifestations in SSc. Several studies have indicated that the serum concentration of CCL2, CCL8, CCL19, CXCL9, CXCL10 and CXCL11 are the most relevant to measure IFN induced activation of PBMCs [3-4]. <h3>Objectives</h3> Here we aimed to determine whether IFN pathway activation measured by a serum test could be used to stratify patients with dcSSc for severe clinical outcome at 12 months as measured by GRCS and CRISS. <h3>Methods</h3> Serum concentration of CCL2, CCL8, CCL19, CXCL9, CXCL10, and CXCL11 was measured by Luminex xMAP technology (Myriad RBM) in 143 SSc patients and 35 healthy controls (HC). IFN score was calculated as the average of the natural logarithm of the above chemokines. IFN score mean + 2STDV in the HC sera was adopted as cut off for IFN LO (within this range) or HI (above) [5]. Clinical outcomes at baseline and at 12 months were recorded. GRCS and CRISS were calculated at 12 months. GRCS were compared by Mann Whitney test. Fisher exact test was used to analyse the proportion of patients with CRISS of 0% or &gt;0%. CRISS and GRCS correlation was tested by Spearman's rank correlation. <h3>Results</h3> All chemokines had a higher serum concentration in SSc vs HC (p&lt;0.0001 for all). Median IFN score was higher in SSc than HC (5.26 vs 4.70, p&lt;0.0001). There was no difference associated with disease subset or duration. To simulate enrollment criteria in a RCT we analyzed the 12 months outcomes of the dcSSc patients with ≤6 years disease duration. Sixty six 12-month outcome data were available. 37 were IFN HI and 29 IFN LO at baseline. The IFN HI group had a higher mRSS (median 9.5 vs 5, p= 0.03), CRP (10.2 vs 5, p=0.0003) and NT-proBNP (195 vs 50.5, p=0.001). We recorded 7 deaths for SSc and 5 lung failures (3 FVC drop, 2 DLCO drop); 3 had worsening of FVC, 4 improvement and 49 no change; 11 had worsening of HAQ-DI, 5 improvement and 43 no change; 9 had worsening of mRSS, 7 improvement and 43 no change (table 1). GRCS ranged from -59 to 64 and was negative in 29 (21 IFN HI, 8 IFN LO) and positive in 37 (16 IFN HI, 21 IFN LO). IFN HI patients had a worse outcome at 12 months with GRCS median score of -12 vs 15 in IFN LO (p=0.0271)(fig. 1). Accordingly, GRCS favored IFN LO in 68.4% of 1073 (37*29) pairwise comparisons versus 31.6% of IFN HI (p=0.0001). CRISS was 0 in 46 (28 IFN HI, 18 IFN LO) and &gt;0 in 20 (9 IFN HI, 11 IFN LO). Spearman's rank correlation of the two scores was r= 0.5113. Consistent with GRCS data, CRISS was 0 in 76% of IFN HI vs 62% of IFN LO (P=0.046). <h3>Conclusion</h3> Serum IFN Score predicts worse clinical outcome at 12 months in dcSSc. Stratification for IFN score could aid both in clinical trial design and clinical management. Moreover, here we show that GRCS and CRISS may be sufficiently sensitive to measure difference in composite outcome at 12 months in dcSSc in an observational setting and they correlate with each other in this observational setting. <h3>References</h3> [1] Sullivan KM. N Engl J Med2018 [2] Khanna D. Arthritis Rheumatol2016 [3] Liu X. Arthritis Rheum2013 [4] Maija-Leena Eloranta. Ann Rheum Dis2010 [5] Bauer JW. PLoS Med2006 <h3>Disclosure of Interests</h3> Antonio Carriero: None declared, Giuseppina Abignano: None declared, Michelle Hutchinson: None declared, Karri Ballard : None declared, Sookhoe Eng: None declared, Paul Emery Grant/research support from: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, Roche, Consultant for: Pfizer, MSD, AbbVie, Bristol-Myers Squibb, UCB, Roche, Novartis, Gilead,Samsung, Sandoz and Lilly, Maya Buch Grant/research support from: Pfizer LTD, UCB, Consultant for: AbbVie, Eli Lilly, EMD Serono, Pfizer Ltd., Sanofi, Francesco Del Galdo: None declared