OBJECTIVES: We describe disease progression in patients from the SLE Prospective Observational Cohort Study (SPOCS; NCT03189875), investigating differences by baseline interferon gene signature (IFNGS) status.

METHODS: Adults with moderate to severe SLE activity receiving SoC were assessed biannually for ≤36 months post-baseline (study entry). SLEDAI-2K, Physician Global Assessment (PGA), SELENA-SLEDAI flare number and severity, SLICC/ACR Damage Index (SDI), and remission (Definition of Remission in SLE [DORIS])/Lupus Low Disease Activity State (LLDAS) attainment were evaluated.

RESULTS: At enrolment (n = 826), mean±S.D. time since SLE diagnosis was 11.1 ± 9.2 years; 70.8% (531/750) of patients were IFNGS-high. At baseline, IFNGS-high vs IFNGS-low patients were younger (42.9 ± 13.6 vs 50.8 ± 12.9 years) and more were using glucocorticoids (68.7% [365/531] vs 56.2% [123/219]). SLEDAI-2K was higher at baseline, month 6, and month 24 in IFNGS-high patients; SLEDAI-2K decreased from baseline to month 36 (9.8 ± 4.6-5.7 ± 7.7) regardless of baseline IFNGS. SDI was lower at baseline, month 12, and month 24 in IFNGS-high patients, but increased over time regardless of baseline IFNGS. By month 36, 44.7% (183/409) experienced ≥1 flare; annualized flare rates were higher in IFNGS-high vs IFNGS-low patients at months 30 and 36. DORIS remission or LLDAS was attained by < 15% and <20% of patients at any timepoint, with no differences between IFNGS groups except lower remission attainment in IFNGS-high patients at month 6.

CONCLUSION: In the SPOCS cohort, disease activity was stable or reduced over time, but treatment target attainment was low and organ damage increased. At month 36, there were no clear differences by baseline IFNGS.

CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov; NCT03189875.