3-YEAR ANALYSES OF AT-RISK ANA-POSITIVE COHORT: PROGNOSTIC VALUE OF CLINICAL AND INTERFERON BIOMARKERS TOWARDS AUTOIMMUNITY

M. Y. MD Yusof, S. U. Hassan, Z. Wigston, A. Psarras, J. Arnold, L. M. Carter, P. Emery, E. VitalUniversity of Leeds, Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom Leeds Teaching Hospitals NHS Trust, NIHR Leeds Biomedical Research Centre, Leeds, United Kingdom  Background Autoimmune connective tissue disease (AI-CTD) arise from a common “At-Risk” ANA-positive population in which clinical phenotype does not reliably predict progression. We previously showed that higher IFN-Score-B and family history were predictive of progression to meeting classification criteria at 12-months[1]. However, classification criteria may undergo revision and not capture all significant outcomes. There is limited data on longer-term outcomes since some may progress at later time-points. Objectives To describe the 3-year outcomes of At-Risk individuals; to assess discriminative ability of baseline clinical and IFN-Score-B in predicting various progression endpoints at 1 and 3 years. Methods We conducted a prospective cohort study in At-Risk individuals (ANA-positive, non-specific symptoms of ≤1 year and treatment naïve). Patients were assessed at baseline, then annually for 3 years. We used multiple RMD classification criteria, including the revised 2019 EULAR/ACR for SLE, and need for therapy, to group patients as below: 1. Absolute non-progressors (ANP) (no clinical criteria) 2. Undifferentiated CTD (U-CTD) (≥1 clinical criteria but not fulfilling RMD criteria). This group was subdivided into those requiring an immunosuppressant (IS) excluding antimalarials only and those who did not) 3. Year 1 progressors (meeting criteria for RMD by 1 year) 4. Late progressors (meeting criteria for RMD in Years 2-3) 5. Clinically significant disease (CSD) (progressors OR U-CTD on IS) Bloods were analysed for two IFN-stimulated gene expression scores previously described[2]. Discrimination of single or combined clinical and IFN-Score-B markers were assessed using ROC curve analyses. Results Of 148 patients, 132 (89%) were female, 107 (72%) were Caucasians, 48 (32%) had a family history of RMD, 56 (38%) were anti-dsDNA+ and 8 (6%) had low C3 and/or C4 level. Number of established clinical criteria at baseline were 0 (30%), 1 (64%) and 2 (6%). Outcomes were: Year 1 progressors: 21 (14%) [SLE=14; pSS=6; AS=1]; Late progressors: 12 (8%) [SLE=10; pSS=1; AS=1]; U-CTD on IS: 8 (5%); U-CTD on antimalarials only: 20 (14%); U-CTD not on therapy: 52 (35%) and ANP: 35 (24%). Thus, 41 (28%) patients were classified as CSD. Only 2/148 (1%) patients progressed after the first 2 years. For the prediction of Year 1 progressor, in addition to baseline IFN-Score-B and family history, multivariable logistic regression showed total number of any established clinical criteria was associated with increased risk, OR 6.8 (95% CI 1.8-25.4). Table 1 showed that the combined baseline markers (IFN-Score-B, family history and number of clinical criteria) had good accuracy in predicting various definitions of progression at Years 1 and 3 as per AUROC. Conclusion Just over a quarter of At-Risk individuals developed into CSD (progressors and patients who did not meet criteria but needed IS therapy) by 3-year follow-up. Combined baseline clinical and IFN biomarkers could be used to risk stratify ANA-positive referrals to rheumatology at the first visit to exclude imminent or future disease/requirement of immunosuppressant. A validation study with cost-effectiveness analysis of these markers is in progress and would help translate their use in clinical practice and inform early therapy trials in the “High Risk” individuals. References Md Yusof MY et al. Ann Rheum Dis 2018 El-Sherbiny Y et al. Sci Rep 2018 Table 1 Progression Criteria No. of Progressors (n/N) AUC (95% CI) for Family History of RMD Only AUC (95% CI) for No. of criteria Only No. of Progressors with samples available (n/N) AUC (95% CI) for IFN-Score-B Only AUC (95% CI) for Combined 3 Markers Year 1 Classification 21/148 0.67 (0.54, 0.80) 0.70 (0.56, 0.81) 20/122 0.81 (0.72, 0.91) 0.89 (0.83, 0.96) Year 1 CSD 26/148 0.65 (0.53, 0.77) 0.70 (0.59, 0.80) 24/122 0.76 (0.66, 0.87) 0.86 (0.77, 0.95) Year 3 Classification 33/148 0.60 (0.49, 0.72) 0.71 (0.61, 0.80) 31/122 0.64 (0.52, 0.76) 0.77 (0.67, 0.87) Year 3 CSD 42/148 0.59 (0.49, 0.69) 0.71 (0.63, 0.80) 40/122 0.59 (0.48, 0.70) 0.74 (0.64, 0.83) Acknowledgements: NIL. Disclosure of Interests Md Yuzaiful Md Yusof Consultant of: Aurinia Pharmaceuticals and UCB, Sabih Ul Hassan: None declared, Zoe Wigston: None declared, Antonios Psarras: None declared, Jack Arnold: None declared, Lucy Marie Carter Consultant of: UCB, Paul Emery Consultant of: Abbvie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Roche and Samsung, Grant/research support from: Abbvie, BMS, Eli Lilly, Pfizer, Novartis, Roche and Samsung, Edward Vital Speakers bureau: AstraZeneca, Novartis, Paid instructor for: AstraZeneca, Novartis, Consultant of: UCB, Pfizer, Aurinia, Lilly, Roche, Genentech, Otsuka, GSK, Capella, Grant/research support from: Sandoz, AstraZeneca. Keywords: Biomarkers, Sjögren syndrome, Systemic lupus erythematosus DOI: 10.1136/annrheumdis-2023-eular.5941Citation: , volume 82, supplement 1, year 2023, page 1078Session: SLE, Sjön’s and APS - clinical aspects (other than treatment) (Poster View)