Effectiveness of leniolisib in reducing infections among patients with activated phosphoinositide 3-kinase δ syndrome (APDS)

APDS is a rare inborn error of immunity characterized by clinical manifestations, including recurrent infections. This real-world, retrospective analysis evaluated patient-reported infection rates before and after leniolisib initiation. Patients (aged ≥ 12 years) newly initiating leniolisib therapy were eligible for inclusion. Data were retrieved from PANTHERx Rare Pharmacy. Patient-reported infection rates during the baseline period (one year before leniolisib initiation) were compared with infection rates after leniolisib initiation (observation period; from initiation to end of data or death) using generalized estimating equations Poisson regression models with robust standard errors. Patients who had an infection assessment collected via a standardized questionnaire during the baseline and observation periods were included in the analysis ( N = 71); subgroups for baseline infection rates (lower and higher than the median) and age (12–17 and ≥ 18 years) were also evaluated. The mean (SD) rate of infections per patient-year (PPY) decreased significantly—by 68%—from 5.8 (5.1) during baseline to 1.9 (2.0) in the observation period (rate ratio [RR], 0.32; 95% CI, 0.24–0.42; P < 0.001); infections PPY decreased by 38% in patients with low baseline infection rates (RR, 0.62; 95% CI, 0.43–0.89; P = 0.010) and 76% in those with high baseline infection rates (RR, 0.24; 95% CI, 0.17–0.34; P < 0.001); infections PPY decreased by 70% in those aged 12 − 17 years (RR, 0.30; 95% CI, 0.20–0.45; P < 0.001) and by 67% in those aged ≥ 18 years (RR, 0.33; 95% CI, 0.23–0.49; P < 0.001). Real-world evidence demonstrated that leniolisib treatment provided a significant reduction in infection rates overall and among subgroups.