OP0128 SYSTEMIC LUPUS ERYTHEMATOSUS DISEASE CHARACTERISTICS ASSOCIATED WITH THE TYPE I INTERFERON GENE SIGNATURE: BASELINE DATA OF THE SLE PROSPECTIVE OBSERVATIONAL COHORT STUDY (SPOCS)
Authors: Edward R. Hammond, Martin Aringer, Laurent Arnaud, Christine Peschken, Jacob Knagenhjelm, Volkan Barut, Xia Wang, Barnabas Desta, Raj Tummala, David Ginkel, Richard Furie, Eric F. Morand
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Despite accumulating data on the role of type I interferons (IFN) in the pathogenesis of SLE, real-world, longitudinal clinical data on the type I IFN gene signature (IFNGS) collected from patients with SLE are limited. <h3>Objectives</h3> This initial analysis of the SLE Prospective Observational Cohort Study (SPOCS; NCT03189875) examined the prevalence of the type I IFNGS (high vs low) and its association with baseline SLE disease characteristics in patients with moderately to severely active SLE receiving standard-of-care treatment. <h3>Methods</h3> SPOCS is an international, multicenter, prospective observational cohort study of patients enrolled with moderately to severely active SLE (SLEDAI-2K ≥6 at entry) from Australia, Canada, France, Germany, Italy, Spain, the United Kingdom, and the United States; a completion date of 2022 is planned. Patients are evaluated biannually during a 3-year follow-up period. At each visit, data are collected on disease activity and damage, treatment received, type I IFNGS (stratified high or low IFNGS based on a predefined cutoff), and several patient-reported outcomes. <h3>Results</h3> As of November 15, 2018, a total of 307 patients were enrolled in SPOCS (North America, n=184; Europe, n=123), of whom 96.1% (n=295) were female, with a median age of 46 years (range: 18–88). At study entry, the prevalence of high type I IFNGS was 70.5% (n=210) vs 27.9% (n=83) for low type I IFNGS, with 1.7% (n=5) unknown (table, 9 missing data). IFNGS-high patients were younger than IFNGS-low patients (median: 42.5 years [range: 18–82] vs 50 [19–88],<i> P</i>&lt;0.0001) and diagnosed with SLE at an earlier age (<i>P</i>&lt;0.0001). SLEDAI-2K scores were greater for IFNGS-high patients vs IFNGS-low patients (<i>P</i>=0.0002), while SDI scores were similar between the two groups. Fewer comorbidities were reported for IFNGS-high patients than for IFNGS-low patients (79.5% [n=167] vs 91.6% [n=76], <i>P</i>=0.0136). Lower complement C3 and C4 levels were observed in IFNGS-high vs -low patients. At study entry, antinuclear antibodies and ribonucleoprotein antibodies were more frequent in the IFNGS-high vs IFNGS-low subset of patients. A greater percentage of IFNGS-high patients were dsDNA antibody positive vs IFNGS-low patients (<i>P</i>=0.0411). <h3>Conclusion</h3> The profile of patients with a baseline high type I IFNGS differed from those with a low type I IFNGS, in that those with a high type I IFNGS comprised a group that were on average younger, had greater SLEDAI-2K scores, were more serologically active, and seemed to have fewer comorbidities. As the lupus community evolves from using a classical clinical classification of patients to one based on molecular signatures, it is important to understand the role of the type I interferon pathway on disease activity, treatment, and outcomes. SPOCS recruitment and follow-up are ongoing. <h3>Disclosure of Interests</h3> Edward R. &nbsp;Hammond Employee of: AstraZeneca, Martin Aringer Grant/research support from: Roche, Consultant for: AstraZeneca and Eli Lilly, Laurent Arnaud Consultant for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugaï, and UCB., Paid instructor for: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugaï, and UCB., Speakers bureau: Alexion, Amgen, AstraZeneca, GSK, Janssen-Cilag, LFB, Lilly, Menarini France, Novartis, Pfizer, Roche-Chugaï, and UCB., Christine Peschken Consultant for: AstraZeneca, Jacob Knagenhjelm Consultant for: I was employed by Dfind Science &amp; Engineering working at AstraZeneca as a contractor statistician from late May 2017 - end April 2018, Employee of: AstraZeneca, Volkan Barut Employee of: AstraZeneca, Xia Wang Shareholder of: AstraZeneca, Employee of: AstraZeneca, Barnabas Desta Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca, David Ginkel Employee of: AstraZeneca, Richard Furie Grant/research support from: Biogen, UCB Pharma, but not in the last 12 months, Consultant for: Biogen, UCB Pharma, but not in the last 12 months, Eric F. Morand Grant/research support from: AstraZeneca, Bristol Myers Squibb, Janssen, Merck Serono, and UCB, Consultant for: AstraZeneca, Eli Lilly, Janssen, and Merck Serono, Speakers bureau: AstraZeneca