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Local Adverse Reaction Rates Decreased over Time during Treatment with Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IGHy) in Patients with Primary Immunodeficiency Disorders in the IGHy Phase 3 Studies
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Mark R. Stein, MD FAAAAI, Richard L. Wasserman, MD PhD FAAAAI, Isaac Melamed, MD, Sudhir Gupta, MD, PhD, FAAAAI, Lisa J. Kobrynski, MD MPH FAAAAI, Arye Rubinstein, MD, FAAAAI, Christopher J. Rabbat, PhD, Werner Engl, PhD, Barbara McCoy, PhD, Heinz Leibl, PhD, Leman Yel, MD, FAAAAI
Rationale: IGHy can be administered at similar doses/volumes and dosing intervals as intravenous immunglobulin G (IgG) (IGIV) but, similar to conventional subcutaneous IgG, is associated with a lower risk of systemic and higher risk of local adverse reactions (ARs). We report local AR rates over time in patients with primary immunodeficiency disorders aged ≥16 years treated with IGHy for up to ~3.5 years in the IGHy pivotal phase 3 study and its extension.

Methods: Following a 3-month IGIV treatment period, patients initiated IGHy on a dose ramp-up schedule and thereafter received IGHy every 3 (Q3W) or 4 weeks (Q4W) for ~18 months, followed by up to an additional 21 months. Local AR (temporally associated and/or causally related adverse events) rates were evaluated over time.

Results: Of the 63 enrolled patients aged ≥16 (16–78) years, 61 were administered IGHy for up to ~3.5 years at the established dose. Overall, the local AR rate per infusion was 0.191; discomfort/pain was the most commonly reported local AR. Rates of ARs per infusion decreased over time: 0.28 (months 1–12), 0.15 (months 13–24), and 0.08 (months 25–33.6). The percentage of patients experiencing ≥1 local AR per infusion was highest during the dose ramp-up period (33.3–41.7% [Q3W] and 29.2–37.5% [QW4]), and rapidly declined over time.

Conclusions: In adults treated with IGHy for up to ~3.5 years, rates of local ARs per infusion and the percentage of patients experiencing ≥1 local AR markedly declined over time.