Long-Term Safety of Facilitated Subcutaneous Immunoglobulin 10% Treatment in US Clinical Practice in Patients with Primary Immunodeficiency Diseases: Results from a Post-Authorization Safety Study

Abstract

Facilitated subcutaneous immunoglobulin (fSCIG) 10% is an immunoglobulin replacement therapy that utilizes recombinant human hyaluronidase (rHuPH20) to enhance immunoglobulin dispersion and absorption, allowing for longer treatment intervals similar to intravenous immunoglobulin (up to once monthly). fSCIG 10% is indicated in the USA for treating adults and children aged ≥ 2 years with primary immunodeficiency diseases (PIDs). This prospective, non-interventional, open-label, multicenter, post-authorization safety study (NCT02593188) was conducted in the USA from November 2015 to October 2021 to assess the long-term safety of fSCIG 10% in routine clinical practice. Patients with PIDs aged ≥ 16 years who were prescribed and/or had started fSCIG 10% treatment were enrolled. In total, 253 patients were enrolled and included (full analysis set). Participants received fSCIG 10% treatment for a median (interquartile range) of 10.0 (3.5-11.8) months, with the majority of infusions administered every 4 weeks (54.4% [1197/2201 infusions]) and at home (62.6% [1395/2230 infusions]). Overall, 98.5% of infusions were administered without rate reduction, interruption, or discontinuation due to adverse events (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). Development of antibodies against rHuPH20 was uncommon; 14/196 patients (7.1%) tested positive for binding antibodies (titer ≥ 1:160) with no neutralizing antibodies detected. There was no relationship between anti-rHuPH20 antibody positivity and the occurrence of treatment-related serious or non-serious AEs. Long-term, repeated self-administration of fSCIG 10% was well tolerated in US clinical practice by patients with PIDs.

Keywords: Immunogenicity; Immunoglobulin replacement; Inborn errors of immunity; Quality of life; Tolerability.

Fig. 1

Study design. ^aFor patients who discontinued fSCIG 10% at any time during Epoch 1 or Epoch 2, only data on adverse events and assessment of anti-rHuPH20 antibodies at the time of routine laboratory assessments were collected. ^bAt the same time as routine laboratory assessments. ^cPatient-reported treatment satisfaction and HRQoL were assessed using questionnaires completed by patients at the screening/enrollment visit, approximately every 3 months during the first year of the study, then annually thereafter, and at the study termination visit (assessed using the Short Form-36 questionnaire version 2, EuroQoL 3-level 5-dimension questionnaire, Treatment Satisfaction Questionnaire for Medication-9, and treatment preference questionnaire). However, the treatment preference questionnaire was collected annually. fSCIG, facilitated subcutaneous immunoglobulin; HCRU, healthcare resource utilization; HRQoL, health-related quality of life; rHuPH20, recombinant human hyaluronidase

Fig. 2

Patient disposition. ^aTwo fatal AEs (possible stress-related complication of chronic lymphocytic leukemia; cardiogenic shock) were reported, neither of which was considered to be treatment-related. ^bOther reasons included: unable to keep timely appointments (n = 2); switched to home infusion and would not complete diary and/or questionnaire (n = 2); switched to home infusion (n = 1); switched to another treatment (n = 1); transferred care (n = 1); did not restart fSCIG 10% (n = 1). ^cParticipant eligible for entry into Epoch 2 (anti-rHuPH20 antibody titer of ≥ 1:160 in Epoch 1) but withdrew consent before entry. AE adverse event, fSCIG facilitated subcutaneous immunoglobulin, rHuPH20 recombinant human hyaluronidase

Fig. 3

Anti-rHuPH20 antibody titers over Epochs 1 and 2. rHuPH20, recombinant human hyaluronidase