FRI0231\u2005IN PATIENTS WITH UCTD, IFN ACTIVITY IDENTIFIES PATIENTS THAT PROGRESS TO DEFINITIVE CTD CLASSIFICATION CRITERIA

Abstract

Background: Undifferentiated connective tissue disease (UCTD) is a term used to describe individuals with positive autoantibodies and symptoms but do not meet criteria for an established autoimmune CTD (AI-CTD). The prognosis of UCTD is unclear, could result in disease stability, remission or progression. As this condition is understudied, there is an unmet need for biomarkers to stratify those who progress to allow for a more aggressive therapy to be employed. IFN plays a major role in the pathogenesis of various AI-CTDs. However there are limited data on its role in AI-CTD. Objectives: To determine whether IFN assays can predict progression from UCTD to meeting classification criteria of established AI-CTDs. Methods: A prospective observational study was conducted on 43 consecutive patients with UCTD; as defined by Mosca criteria [1]. Progression was defined by meeting 2012 ACR/SLICC SLE, 2016 ACR/EULAR Primary Sjogren’s, Bohan-Peter, 2013 ACR/EULAR Scleroderma, or 2006 Sydney Antiphospholipid syndrome criteria. For the interferon scores, RNA was extracted from PBMCs and a custom Taqman array was used to measure expression of 30 interferon stimulated genes (ISGs) as previously described [2]. A two-score system of ISGs (IFN-Score-A and Score-B), was calculated without the knowledge of participants’ clinical status. Results: Mean (range) age of the cohort was 48 (39-58) years; Female 36 (84%); mean disease duration 5.5 years; concomitant DMARDs including anti-malarials 38 (88%), concomitant corticosteroid 2(5%) and internal organ involvement 9 (21%). At the follow-up visit, 9/43 (21%) met established classification criteria for AI-CTD [SLE=6; IIM=2; and SSc=1]. Comparing the IFN scores between those who progressed (n=9) vs those remained undifferentiated (n=34); the IFN-Score-A was higher in the progressor group; fold difference (FD) 2.76 (95% CI 1.11-6.88); p=0.030. While for IFN-Score-B, there was a trend to association for higher expression in the progressor group vs remained undifferentiated; FD 1.74 (0.53-3.21); p=0.077. Conclusion: IFN assays can identify progression to classifiable CTD within cohorts of UCTD. There is a potential role for the use of IFN biomarkers in the prognostication of patients with UCTD. References: [1] Mosca M, Neri R & Bombardieri S. 1999. UCTD: a review of the literature and a proposal for preliminary classification criteria. Clin Exp Rheumatol; 17: 615-620 [2] El-Sherbiny YM, Psarras A, Yusof MY Md, Hensor EMA, Tooze R, Doody G, Mohamed AAA, McGonagle D, Wittmann M, Emery P & Vital E Acknowledgement: We acknowledge no conflicts of interest Disclosure of Interests: Katherine Dutton Speakers bureau: Pfizer, Md Yuzaiful Md Yusof: None declared, Sabih-Ul Hassan: None declared, Zoe Wigston: 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, Edward Vital Grant/research support from: He has received honoraria and research grant support from Roche, GSK and AstraZeneca.