Comparison of hyaluronidase-facilitated subcutaneous immunoglobulin 10% pharmacokinetics in pediatric and adult patients with primary immunodeficiency: an analysis of three phase 3 clinical trials

Abstract Introduction Facilitated subcutaneous immunoglobulin (fSCIG) 10% is approved for the treatment of primary immunodeficiency (PID) in both pediatric and adult patients. However, it remains unclear whether there is a clinically meaningful difference in the pharmacokinetics (PK) of immunoglobulin G (IgG) between these two populations. Methods Serum total IgG concentrations in pediatric and adult patients (aged 3–80 years) with PID from three phase 3 clinical trials of fSCIG 10% were analyzed (NCT00814320, NCT01175213, NCT03277313). Serum total IgG trough concentrations (Ctrough) were compared against the conservative threshold for treatment effectiveness of 7 g/L, and between adult and pediatric patients (aged 2 to <17 years) and pediatric subgroups (2 to <12 years and 12 to <17 years). PK parameters, including steady-state maximum concentration (Cmax), area under the curve during the dosing interval, normalized by week (AUC/week), and apparent clearance normalized for body weight (CL/F/BW), were also compared across age groups. Results All age groups effectively achieved mean IgG Ctrough above 7 g/L following fSCIG 10% administration. Total IgG exposures (mean Ctrough, Cmax, and AUC/week) marginally increased with age (all P < 0.05), while there was considerable variability within age groups. However, after total IgG baseline correction, there were no differences any exposure parameters by age. CL/F/BW remained consistent across studies and age groups. Conclusion fSCIG 10% effectively maintains total IgG trough concentrations in IgG treatment-experienced patients with PID. The small age-related differences observed in serum total IgG PK are unlikely to be clinically significant and dose adjustments by age alone are not warranted.