Burden of systemic lupus erythematosus in clinical practice: baseline data from the SLE Prospective Observational Cohort Study (SPOCS) by interferon gene signature

Abstract

Objective The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity.Methods SPOCS (NCT03189875) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria. Enrolled patients from 135 centres in 8 countries were followed biannually for ≤3 years from June 2017 to November 2022. Baseline demographics, disease characteristics, organ system involvement/damage and flares were analysed descriptively according to SLE Disease Activity Index-2000 score (SLEDAI-2K <10/≥10) and IFNGS status (high/low).Results The study population (n=823) was 93.2% female, with mean (SD) age 45.3 (13.9) years and 11.1 (9.2) years since diagnosis; 52.4% had baseline SLICC/ACR Damage Index score ≥1. Patients with SLEDAI-2K scores ≥10 (241 of 584, 41.3%) vs <10 were younger (mean 42.8 (13.7) vs 46.6 (14.2) years; nominal p=0.001), had shorter SLE duration (10.4 (8.6) vs 12.4 (9.6) years; nominal p=0.012) and more severe flares (12.9% vs 5.3%; nominal p=0.001). IFNGS-high patients (522 of 739, 70.6%) were younger than IFNGS-low patients at first SLE manifestation (30.0 (12.7) vs 36.8 (14.6) years; nominal p<0.001). Proportions of IFNGS-high patients differed according to race (nominal p<0.001), with higher proportions among Asian (83.3%) and black (86.5%) versus white patients (63.5%). Greater proportions of IFNGS-high versus IFNGS-low patients had haematological (12.6% vs 4.1%), immunological (74.4% vs 45.6%) or dermal (69.7% vs 62.2%) involvement.Conclusions We identified key characteristics of patients with high disease activity and/or elevated type I IFN signalling, populations with SLE with high unmet needs. Baseline SLEDAI-2K ≥10 was associated with shorter disease duration and more severe flares. IFNGS-high patients were younger at diagnosis and had distinct patterns of organ involvement, compared with IFNGS-low patients.