PO:14:203 | Impact of anifrolumab on depressive symptoms in systemic lupus erythematosus: results from a single-centre prospective observational study

Luca Moroni¹, Biancamaria Venerandi¹, Maria Cilona¹, Anna Vivona¹, Gabriele Gallina¹, Giovanni Benanti¹, Enrica Bozzolo¹, Giuseppe Ramirez¹, Marco Matucci-Cerinic¹, Lorenzo Dagna¹. | ¹U.O. di Immunologia, Reumatologia, Allergologia e Malattie Rare - IRCCS Ospedale San Raffaele, Milano, Italy.

Background. Systemic Lupus Erythematosus (SLE) is a complex autoimmune disease characterised by multisystem involvement, where neuropsychiatric manifestations, including depression, are prevalent. Dysregulated activation of the type I interferon (IFN) pathway contributes to SLE pathogenesis and has been implicated in depressive behaviour through mechanisms such as serotonin modulation and neurogenesis inhibition. Anifrolumab, a monoclonal antibody targeting the Type I IFN receptor, is effective in reducing SLE disease activity and glucocorticoid burden. However, its potential impact on depressive symptoms remains underexplored. The aim of this study is to assess the impact of intravenous anifrolumab 300 mg on depressive symptoms in adult patients with moderately to severely active SLE, alongside secondary outcomes evaluating patient-reported quality of life.

Materials. This single-centre, prospective, observational study enrolled adult SLE patients meeting 2019 EULAR/ACR classification criteria with autoantibody positivity and active disease (SLEDAI-2K >=6). Participants received 300 mg of anifrolumab intravenously every 4 weeks in combination with standard-of-care (SOC). Depression severity was assessed using Beck’s Depression Inventory (BDI) and Patient Health Questionnaire-9 (PHQ-9) at baseline, 3, 6, and 12 months. Patient-reported outcomes included FACIT score and Lupus Quality of Life (Lupus QoL). Wilcoxon signed-rank test was used to compare with baseline median values of all variables at different timepoints. Cohen’s effect size was calculated to outline clinical impact of treatment.

Results. Thirty-two (32) patients have been enrolled. Female sex is predominant (n=25; 78%), with a mean age of 46 (SD ± 14.0) and disease duration of 11 years (SD ± 9). The commonest disease manifestations were cutaneous and musculoskeletal, observed in 93% of the sample. Four patients (14%) had a history neuropsychiatric SLE. A clinically relevant reduction in median BDI and PHQ-9 scores was observed at 12 months compared with baseline (Cohen’s d -0.51 and -0.26 respectively) (Figure1). FACIT and LupusQoL scores exhibited strong improvement (Cohen’s d -0.62 and +0.97 respectively at 12 months). Lupus QoL improvement was obsterved in all domains, particularly pain (12.0 vs. 8.0, p=0.018, effect size +0.98), and burden to others (12.0 vs 7.0, p=0.017, effect size +0.97) (Table 1). Moreover, anifrolumab improved systemic and cutaneous disease activity at 12 months (median SLEDAI-2k 4.0 vs. 8.5 at baseline, p=0.002; median CLASI-A 0.0 vs. 3.0 at baseline, p=0.015). All 11 patients treated for at least 12 months were glucocorticoid-free at last follow-up and 8 (73%) met DORIS remission criteria.

Conclusions. Anifrolumab may alleviate depressive symptoms in patients with SLE and may also improve both their quality of life and disease activity. These findings suggest that, by the inhibition of interferon signalling, anifrolumab may contribute to the improvement of depressive symptoms.