Biologic IgG level in primary immunodeficiency disease: The IgG level that protects against recurrent infection

Bonagura, Vincent R.; Marchlewski, R.J.; Cox, Amanda; Rosenthal, David W.

doi:10.1016/j.jaci.2008.04.044

Cited by 150 publications

(94 citation statements)

References 6 publications

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“…A patient-individualized approach to IgG replacement therapy is supported by clinical experience and justified by a prospective analysis in patients with common variable immunodeficiency disorders over a follow-up period of 22 years. 21,22 Protective IgG trough levels were achieved with a wide range of replacement doses (0.2-1.2 g/kg/mo), whereas patients with bronchiectasis required twice as much IgG replacement therapy. 21,23 In most of our patients, the mean trough total IgG level was maintained in the range 7.56 to 7.98 g/L.…”

Section: Discussionmentioning

confidence: 99%

Pneumococcal Antibody Levels in Children With PID Receiving Immunoglobulin

et al. 2014

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OBJECTIVES: Clinical data are lacking on optimal levels of specific antipneumococcal antibodies (PnPsAbs) in patients with primary immunodeficiency (PID) receiving intravenous immunoglobulin (IVIG) replacement. Objectives were to conduct a prospective multicenter study providing data on total immunoglobulin G (IgG) and peak/trough levels of PnPsAbs specifically targeting the 16 most prevalent pneumococcal serotypes in IVIG-treated children with PID; to compare trough PnPsAb levels with those measured in healthy adults and the IVIG product; and to evaluate PnPsAb protection correlates with thresholds based on World Health Organization. METHODS: Patients received 7 consecutive IVIG infusions. Total IgG and PnPsAb levels were determined on plasma samples obtained before and after infusion. RESULTS: Twenty-two children with PID were treated with IVIG (mean weekly dose: 0.10 g/kg). The mean trough and peak levels of total IgG were 7.77 and 13.93 g/L, respectively. Trough and peak geometric mean concentrations and distribution curves differed between serotypes and showed wide dispersion (0.17–7.96 µg/mL). In patients (89%–100%), antibodies against most serotypes reached trough levels ≥0.2 µg/mL, a threshold considered protective against invasive pneumococcal infection. For several serotypes, trough levels reached ≥1.0 to 1.3 µg/mL, the level found in adults. Trough geometric mean concentrations correlated well with the PnPsAb contents of the IVIG product. CONCLUSIONS: In IVIG-treated children with PID, protective PnPsAb levels for most pathogenic serotypes were obtained. A correlation was observed between PnPsAb levels in patients and in the IVIG product. This offers the potential to improve infection prevention by adapting the IVIG product and dose according to epidemiology.

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Section: Discussionmentioning

confidence: 99%

Pneumococcal Antibody Levels in Children With PID Receiving Immunoglobulin

et al. 2014

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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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“…The appropriate trough to minimize infections is individual to each patient [40,41]. By protocol, the minimum IgG trough level in the study was 500 mg/dl.…”

Section: Pharmacokinetic Propertiesmentioning

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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Biologic IgG level in primary immunodeficiency disease: The IgG level that protects against recurrent infection

Cited by 150 publications

References 6 publications

Pneumococcal Antibody Levels in Children With PID Receiving Immunoglobulin

Pneumococcal Antibody Levels in Children With PID Receiving Immunoglobulin

Bioavailability of IgG Administered by the Subcutaneous Route

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

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