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BackgroundSubcutaneous immunoglobulin (IGSC) replacement therapy for primary immunodeficiency (PI) is equally efficacious to intravenous immunoglobulin (IGIV), induces fewer systemic reactions, and may be self-infused. Limited SC infusion volumes and reduced bioavailability, however, necessitate multiple infusion sites, more frequent treatment, and dose adjustment to achieve pharmacokinetic equivalence. Recombinant human hyaluronidase (rHuPH20) increases SC tissue permeability and facilitates dispersion and absorption, enabling administration of monthly doses in one site.ObjectiveThis study investigated the efficacy and tolerability of rHuPH20-facilitated IGSC (IGHy) in patients with PI.MethodsIn this open-label, multicenter phase III study, 87 patients with PI aged ≥2 years received 10% IGIV for 3 months, then IGHy (n = 83) for approximately 14 to 18 months at 108% of the IGIV dose. IGHy infusions began weekly, increasing to 3- or 4-week intervals.ResultsThe majority (94.0%) of IGHy infusions were administered every 3 or 4 weeks, using one site (median, 1.09/month), with a mean volume of 292.2 mL. The bioavailability of IGHy measured by area under the concentration versus time curve was 93.3% of IGIV, which is pharmacokinetically equivalent. Systemic reactions were less frequent with IGHy than with IGIV (8.3% vs 25.0% of infusions). Local reactions to IGHy were generally mild to moderate, with a rate of 0.203 per infusion. The acute serious bacterial infection rate per subject-year for IGHy was low (0.025; upper 99% CI limit, 0.046). Overall infection rates per subject-year were 2.97 for IGHy and 4.51 for IGIV.ConclusionIGHy was effective, safe, and pharmacokinetically equivalent to IGIV at the same administration intervals, but it caused fewer systemic reactions. Tolerability was good despite high infusion volumes and rates.

Treatment decisions made in clinical practice, based on current guidelines, often conflict with decisions by third-party payors that restrict the ability of patients with primary immunodeficiency disease (PI) to adhere to appropriate treatment. This is seen by many physicians as potentially placing the health of patients at risk. Key treatment decisions challenged by third-party payors and discussed here include dosing, product safety, and routes of administration. Data on safety issues emphasize that IgG products are not generic drugs and each of the products currently licensed by the Food and Drug Administration (FDA) must be regarded as an individual therapy, given the products' different manufacturing processes and stabilizing ingredients. The issue of switching patients to a different product needs careful consideration as evidence shows that infusion-related adverse events in many patients are frequently related to this activity. Decisions regarding the route of therapy should also be individualized to the patient, weighing such factors as side effects, adherence with therapy, and lifestyle. [ABSTRACT FROM AUTHOR]

Since 2005, when changes in Medicare reimbursement for IgG replacement therapy went into effect, physicians and patients with primary immunodeficiency disease (PIDD) have encountered a number of challenges to administering and receiving appropriate immunoglobulin therapy. A 2006 membership survey conducted by the American Academy of Allergy, Asthma & Immunology found that 95 % of responders thought that the health of their patients was at risk due to Medicare changes; many patient surveys also found a significant number adversely affected by these changes. Decisions critical for optimal care being made by third-party payors are often in conflict with guidelines on recommended standard of care. Many payors, for example, are dictating where infusions can occur despite evidence clearly demonstrating that choice of the site of care needs to be determined by the particular patient's circumstance and experience. Another critical issue is the lack of product availability due to the determination by payors of which IgG products appear on formularies. Patients, physicians, and payors all bring their own perspective to these issues, and finding a solution to these challenges requires balancing the needs of all three groups. [ABSTRACT FROM AUTHOR]