Incidence of Infection is Inversely Related to Steady-State (Trough) Serum IgG Level in Studies of Subcutaneous IgG in PIDD

Berger, Melvin

doi:10.1007/s10875-011-9546-2

Cited by 34 publications

(31 citation statements)

References 17 publications

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“…In the EU study [15] [16][17][18][19][20][21][22][23][24], and for the postefficacy period (Weeks 30-36), to be sure that a steady state was achieved. The mean serum IgG levels were calculated by averaging individual patient's median values at each time period.…”

Section: Methodsmentioning

confidence: 99%

Bioavailability of IgG Administered by the Subcutaneous Route

Berger¹,

Jolles²,

Sleasman³

2012

Journal of Allergy and Clinical Immunology

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Purpose US licensing studies of subcutaneous IgG (SCIG) calculate dose adjustments necessary to achieve area under the curve (AUC) of serum IgG vs. time on SCIG that is noninferior to that on intravenous IgG (IVIG), within the FDAset limit of ±20 %. The results are interpreted as showing that different SCIGs differ in bioavailability. We used three approaches to determine if the bioavailabilities were actually different. Methods Dose adjustments and AUCs from published licensing studies were used to calculate bioavailabilities using the formula: Bioavailability (% of IVIG) = AUC(SCIG) ÷ AUC(IVIG) x 1/Dose Adjustment. We also compared the increment in serum IgG concentration achieved with varying doses of SCIG in recent meta-analyses with the increment with different doses of IVIG, and determined the serum IgG concentrations when patients switched SCIG products at the same dose. Results The actual bioavailabilities were: Gamunex® 65.0 %, Hizentra® 65.5 %, Gammagard® 67.2 %, Vivaglobin® 69.0 %. Regression analyses of serum IgG vs. dose showed that the mean increase in serum IgG resulting from a 100 mg/kg/month increment in SCIG dosing was 69.4 % of the increase with the same increment in IVIG dosing (84 mg/dL vs. 121 mg/dL). Patients switching SCIG preparations at the same dose had no change in serum IgG levels, confirming that bioavailabilities of the SCIG preparations did not differ.Conclusions Decreased bioavailability appears to be a basic property of SCIG and not a result of any manufacturing process or concentration. Because serum IgG levels do not vary with different SCIG products at the same dose, adjustments are not necessary when switching products.

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Section: Methodsmentioning

confidence: 99%

Bioavailability of IgG Administered by the Subcutaneous Route

Berger¹,

Jolles²,

Sleasman³

2012

Journal of Allergy and Clinical Immunology

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“…Immunoglobulin replacement therapy must therefore be tailored for each individual patient [46]. Subcutaneous infusion with IGHy provides options for individualized treatment that minimizes the impact of IgG replacement therapy on patients' lives.…”

Section: Anti-ph20 Immunogenic Responsementioning

confidence: 99%

Recombinant Human Hyaluronidase-Facilitated Subcutaneous Immunoglobulin Infusion in Primary Immunodeficiency Diseases

Wasserman

2017

Immunotherapy

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Most primary immunodeficiency diseases (PIDDs) resulting in antibody deficiency require intravenous or subcutaneous immunoglobulin G (SCIG) replacement therapy. The flow and distribution of SCIG to the vasculature is impeded by the glycosaminoglycan hyaluronan in the extracellular matrix, which limits the infusion rate and volume per site, necessitating frequent infusions and multiple infusion sites. Hyaluronidase depolymerizes hyaluronan and is a spreading factor for injectable biologics. Recombinant human hyaluronidase (rHuPH20) increases SCIG absorption and dispersion. In patients with PIDD, SCIG facilitated with rHuPH20 (IGHy) has been shown to prevent infections, be well-tolerated and reduce infusion frequency and number of infusion sites as compared with conventional SCIG. This article reviews IGHy clinical studies and real-world practice data in patients with PIDD.

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“…In those patients with humoral immunodeficiency, antibody production is decreased or of poor quality, leading to severe, recurrent infections that are predominantly bacterial sinopulmonary infections [1]. Historically, lifelong treatment of these types of PID with immunoglobulin (Ig) through various routes (e.g., intravenous (IV), subcutaneous (SC), intramuscular) has been wellestablished and has been shown to decrease the incidence of infections in these patients [1][2][3][4][5][6][7][8][9][10]. Moreover, SCIg therapy has been shown through several studies to be effective, safe, and well-tolerated in patients with PID [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Section: Introductionmentioning

confidence: 99%