Session Information
Date: Sunday, November 12, 2023
Title: (0543–0581) SLE – Diagnosis, Manifestations, & Outcomes Poster I
Session Type: Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Many rheumatologists find it challenging to safely discharge “At-Risk” ANA-positive people at the first visit due to lack of cardinal signs and prediction tools. “Watch and wait” approach is not cost-effective and delay appropriate care of non-immune pathology. 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. Our study objectives were to describe the 3-year outcomes of At-Risk cohort and 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 people (ANA-positive ≥1:80, new referral with 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: i) Absolute non-progressor (ANP) (no clinical criteria); ii) Undifferentiated CTD (U-CTD) (≥1 clinical criteria but not full RMD criteria). This group was subdivided into those requiring immunosuppressant (IS) excluding antimalarials only and those who did not; iii) Year 1 progressor (meeting criteria for RMD by 1 year); iv) Late progressor (meeting criteria for RMD in Years 2-3); v) Clinically significant disease (CSD) (progressor 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, mean (SD) age was 47 (15) years, 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. No. of 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] of which only 2/12 in Year 3; U-CTD on IS: 8 (5%); U-CTD on antimalarials only: 20 (14%); U-CTD not on therapy: 50 (34%) and ANP: 37 (25%). Thus, 41 (28%) was classified as CSD by 3-year. For the prediction of Year 1 progressor, in addition to baseline IFN-Score-B and family history, multivariable regression showed no. of clinical criteria was associated with increased risk, OR 7.8 (95% CI 1.7-36.3). Table 1 showed that combined baseline markers (IFN-Score-B, family history and no. of clinical criteria) had good accuracy in predicting various definitions of progression at Years 1 and 3 as per AUROC.
Conclusion: About a quarter of At-Risk people developed CSD by 3-year, mostly did so within Year 1. Combined baseline clinical and IFN biomarkers had high specificity and could be used to risk stratify new ANA-positive referrals to rheumatology 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.
References: 1. Md Yusof et al. ARD 2018, 2. El-Sherbiny et al. Sci Rep 2018
To cite this abstract in AMA style:
Md Yusof M, Ul-Hassan S, Wigston Z, Psarras A, Arnold J, Carter L, Emery P, Vital E. Clinical and Interferon Biomarkers to Exclude Imminent Autoimmune Disease in ANA Positive Individuals [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/clinical-and-interferon-biomarkers-to-exclude-imminent-autoimmune-disease-in-ana-positive-individuals/. Accessed .« Back to ACR Convergence 2023
ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-and-interferon-biomarkers-to-exclude-imminent-autoimmune-disease-in-ana-positive-individuals/