Reported Infections Lower After Leniolisib Start in APDS

Key Takeaways

• Among adolescents and adults with APDS newly starting leniolisib, patient-reported infections per patient-year were 68% lower after initiation than during the preceding year.
• Reported infection rates declined significantly in both the lower- and higher-baseline-infection groups, by 38% and 76%, respectively.
• Adolescents and adults each had significant declines in reported infection rates, of 70% and 67%, respectively.

Recurrent infections are a feature of activated phosphoinositide 3-kinase δ syndrome (APDS), a rare inborn error of immunity. For affected adolescents and adults, the clinical question is how frequently they reported infections before and after starting leniolisib. Reports collected across both periods allow investigators to compare infection frequency without assuming that any change represents infections prevented by treatment.

Investigators used PANTHERx Rare Pharmacy data for a retrospective study of leniolisib and patient-reported infections in APDS. Patients newly initiating leniolisib at age 12 years or older were eligible; 71 had infection assessments collected through a standardized questionnaire in both periods. Each patient's year before initiation served as the baseline comparator for an observation period extending from initiation until the end of available data or death. The measured outcome was patient-reported infections per patient-year. Investigators evaluated patterns by age and baseline infection burden, using generalized estimating equations Poisson regression with robust standard errors for the before-and-after rate comparison.

Patient-reported infections were less frequent after leniolisib initiation in the overall group. Mean infections per patient-year, with standard deviation (SD) in parentheses, were 5.8 (5.1) before versus 1.9 (2.0) afterward. The estimated rate ratio (RR) was 0.32 (95% confidence interval [CI] 0.24–0.42), with P<0.001. These estimates compare reported infection frequency in two periods for the same patients, not outcomes in patients who did not start leniolisib.

Lower patient-reported infection rates after initiation were also observed in both baseline-infection-burden strata. Declines were statistically significant within the lower- and higher-burden strata and within the adolescent and adult strata. These findings describe changes within each subgroup, not differences in the size of those changes between subgroups.

The retrospective comparison used each patient's preceding year as the reference period rather than a concurrent untreated group. Other changes over time could therefore contribute to the difference in reported frequency, and the association does not establish that leniolisib prevented infections. The endpoint was infections reported by patients through questionnaire assessments, not an independently verified measure of infection events. Interpretation is confined to patient-reported infection rates during the defined periods.

Investigators associated leniolisib initiation with lower patient-reported infection frequency overall and in the examined baseline-burden and age subgroups. The findings remain within-person observations rather than evidence of infections prevented.

Clinician Questions

How were baseline infection-burden groups defined for patients with APDS starting leniolisib?

In this retrospective analysis of patients with APDS starting leniolisib, investigators grouped baseline patient-reported infection rates as lower or higher than the median.

Do different declines in adolescents and adults with APDS prove an age-dependent leniolisib effect?

No age-dependent difference was demonstrated. Investigators reported declines separately for adolescents aged 12–17 years and adults aged at least 18 years, but did not report a direct statistical comparison of changes between age groups.