CLINICAL EFFICACY, SAFETY, AND IMPACT ON PERIPHERAL BLOOD IMMUNOPHENOTYPES OF ANIFROLUMAB IN SLE PATIENTS WITH MINOR FLARES FOLLOWING LLDAS ACHIEVEMENT: LOOPS REGISTRY AND FLOW STUDY

PV268 / #674 Poster Topic: AS24 - SLE-Treatment Background/Purpose Anifrolumab (AFM) has demonstrated efficacy and safety in patients with systemic lupus erythematosus (SLE), but the effect of type I interferon modulation on the immune abnormalities in these patients is unclear. This study aimed to investigate the relationship between changes in immune phenotype and the efficacy of AFM in patients with SLE who experienced minor flares after lupus low disease activity state (LLDAS). Methods Patients with SLE who achieved LLDAS but experienced minor flares due to mild or moderate organ damage according to the clinical items of the revised SELENA flare index were divided into 2 groups: Those who received standard of care (SoC, n = 18) with increased glucocorticoid (GC) doses or additional immunosuppressants and those who received only additional AFM treatment (n = 50). Effectiveness and safety were compared 26 weeks after intensification using propensity score-based inverse probability of treatment weighting (PS-IPTW). Peripheral blood immunophenotypes at baseline were analyzed and compared with age- and sex-matched healthy controls (HC, n=70) about the standardized NIH/FOCIS Human Immunophenotyping Consortium protocol. Immunophenotype changes and their impact on re-achieving LLDAS at Week 26 were also analyzed in SLE patients who experienced minor flares after LLDAS. Results After PS-IPTW adjustment, there were no differences in baseline characteristics between the groups. The 26-week persistence rate of the AFM group was 90.0% (45/50). The LLDAS achievement rate was significantly higher in the AFM group (SoC group: AFM group = 33%:87%, p < 0.001). The SELENA-SLEDAI scores significantly decreased in both groups, and no significant difference was observed between the groups at 26 weeks (SoC group: AFM group = 2.1±2.0:1.8±1.7, p = 0.453). The mean dose of GC was markedly reduced in the AFM group (3.6±3.1→2.1±2.7, p < 0.001), and the GC mean dose at Week 26 was significantly lower in the AFM group (SoC group: AFM group = 5.7±1.8:2.1±2.7, p < 0.001), leading to GC discontinuation in 3 patients. The incidence of adverse events was significantly lower in the AFM group (SoC group: AFM group = 47%:12%, p < 0.001), particularly for infections (SoC group: AFM group = 38%:12%, p < 0.001). In peripheral blood immunophenotype analysis, in comparison with HC, SLE patients had a higher proportion of activated Tfh cells (p=0.003), activated Th17 cells (p=0.0025), and plasmocytes (p=0.015), and a lower proportion of naïve B cells (p=0.010). There were no significant differences in baseline immunophenotypes between the AFM and SoC groups. At 26 weeks, both groups exhibited decreased plasmocyte proportions. In the AFM group, the proportions of activated Th17 cells (p = 0.014), Tfh cells (p < 0.001), and activated Tfh cells (p = 0.018) significantly decreased at 26 weeks compared to baseline. In both the SoC group and the AFM group, no baseline clinical features were associated with achieving LLDAS or DORIS remission. However, in the AFM group, patients with a higher baseline proportion of plasmocytes were more likely to achieve DORIS remission. In the SoC group, there were no peripheral blood immune phenotype characteristics associated with LLDAS or DORIS remission. Conclusions In SLE patients who experience a minor flare after achieving LLDAS, disease activity may be effectively controlled by adding AFM alone, without the need to increase immunosuppressants or glucocorticoids. Among these patients, AFM appears to be particularly effective in those with a high baseline proportion of plasmocytes prior to its initiation.

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