Bioavailability of IgG Administered by the Subcutaneous Route
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 non-inferior to that on intravenous IgG (IVIG), within the FDA-set 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.
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.
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.
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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- Bioavailability of IgG Administered by the Subcutaneous Route
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Journal of Clinical Immunology
Volume 33, Issue 5 , pp 984-990
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Subcutaneous IgG (SCIG)
- IgG dose adjustments
- intravenous IgG (IVIG)
- Industry Sectors
- Author Affiliations
- 1. CSL Behring LLC, King of Prussia, PA, 19406, USA
- 2. Department of Medical Biochemistry and Immunology, University Hospital of Wales, Cardiff, UK
- 3. Texas Children’s Hospital, Section of Immunology Allergy and Rheumatology, Baylor College of Medicine, Houston, TX, USA
- 4. Department of Pediatrics, University of South Florida, St. Petersburg, FL, USA