Long-term safety of facilitated subcutaneous immunoglobulin 10% treatment in patients with primary immunodeficiency diseases: final analysis from a post-authorization safety study conducted in the USA

Abstract

IntroductionFacilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption. fSCIG 10% is approved in the USA for adult patients with primary immunodeficiency diseases (PIDDs). This study aimed to assess the long-term safety of fSCIG 10% in routine clinical practice. MethodsThis prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from Nov-2015 to Aug-2022. Patients with PIDD, aged ≥16 years, prescribed or receiving fSCIG 10% were enrolled. Treatment regimens were planned by the attending physician in accordance with routine clinical practice. Adverse event (AE) data were collected from enrollment to study completion or discontinuation and the presence of anti-rHuPH20 antibodies was evaluated on a voluntary basis. ResultsIn total, 253 patients were enrolled and included in the full analysis set (mean age [standard deviation] 54.3 years [15.6]; 79.1% female). The most common PIDD diagnosis was common variable immunodeficiency (71.9%). Patients received fSCIG 10% treatment for a median (interquartile range) duration of 10.0 (3.7–11.8) months, with most infusions administered every 4 weeks (54.4% [1197 of 2201 infusions]) at home (62.6% [1395 of 2230 infusions]). Overall, 98.5% of infusions were administered without a rate reduction, interruption, or discontinuation due to AEs. Treatment-related, non-serious AEs were experienced by 52 patients (20.6%, 284 events). Two patients (0.8%) each experienced one treatment-related serious AE (aseptic meningitis and deep vein thrombosis). Two fatal AEs (0.8%) were reported; neither were treatment-related. Of 196 patients tested, 14 (7.1%) were positive for treatment-emergent binding anti-rHuPH20 antibodies (titer ≥1:160; maximum titer 10 240); no neutralizing antibodies were detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. ConclusionsLong-term, repeated, self-administration of fSCIG 10% is well-tolerated in US clinical practice by patients with PIDD. Development of non-neutralizing antibodies against rHuPH20 was uncommon and did not correlate with treatment-related AEs.Baxalta US Inc., a Takeda company, funded this study. Takeda Pharmaceuticals International AG funded writing support.