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Fatigue outcomes with anifrolumab in low-disease-activity SLE: DNA damage in plasmacytoid dendritic cells as a candidate biomarker for responders

Year: 2026

Type: article

Abstract: Objective Investigate the effect of anifrolumab on fatigue in patients with SLE and low disease activity and identify cellular mechanisms associated with the fatigue response.Methods 12 SLE patients with significant fatigue (Fatigue Assessment Scale (FAS) 1 ≥22) initiating anifrolumab were followed at baseline, 1 month and 3 months. The primary endpoint was fatigue improvement (FAS reduction ≥4 points). Secondary endpoints included FAS, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Generalised Anxiety Disorder-7, Quick Inventory of Depressive Symptomatology Self-Report-16, serum interferon (IFN)-α, type I IFN activity and γH2AX expression in myeloid subsets by flow cytometry.Results Median baseline SLEDAI was 4 (IQR 4–7) and median FAS was 28 (IQR 24–36). Fatigue improvement, defined by FAS reduction ≥4 points, was observed in 58% of patients (7/12; 95% CI 29% to 88%) at 3 months. Serum IFN-α was low across the cohort and did not predict response. Baseline γH2AX in plasmacytoid dendritic cells (pDCs) was significantly higher in responders than in non-responders and healthy controls and showed a declining trend after 1 month of treatment (Wilcoxon signed-rank test, n=6, p=0.156).Conclusions These preliminary findings suggest that anifrolumab may improve fatigue in patients with SLE including those with low disease activity and low serum IFN-α. Elevated pDC γH2AX at baseline, reflecting subclinical cellular stress, may identify patients who could benefit from IFN blockade for fatigue. These hypothesis-generating findings warrant validation in controlled studies.

Source: Lupus Science & Medicine

DOI: 10.1136/lupus-2026-002234