Pharmacokinetics and safety of subcutaneous immune globulin (human), 10% caprylate/chromatography purified in patients with primary immunodeficiency disease

Wasserman, Richard L.; Irani, Anne-Marie; Tracy, James M.; Tsoukas, Chris; Stark, Donald; Levy, Robyn J.; Chen, J.; Sorrells, Susan C.; Roberts, Robert L.; Gupta, Sudhir

doi:10.1111/j.1365-2249.2010.04195.x

Cited by 66 publications

(53 citation statements)

References 29 publications

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“…Adjusting the dose to achieve the same AUC is considered necessary because of presumed differences in the bioavailability of IgG and similar proteins when given by the intramuscular (IM) or subcutaneous (SC) routes as compared with the intravenous (IV) route [2]. Dose adjustments of 120 % to 153 % have been used in different studies of polyclonal SCIG, implying that the different products have different bioavailabilities [3][4][5][6]. However, "non-inferiority" designs, which accept a margin of ±20 % of AUC, have been employed, so the derived dose adjustments may not reflect the actual bioavailability of different products [1].…”

Section: Introductionmentioning

confidence: 99%

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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: Introductionmentioning

confidence: 99%

“…SCIG is commonly used as replacement therapy in patients with PID [3][4][5][6][7][8]. It has also been successfully tried in autoimmune peripheral neuropathies [9].…”

Section: Introductionmentioning

confidence: 99%

Bioavailability of IgG Administered by the Subcutaneous Route

Berger¹,

Jolles²,

Sleasman³

2012

Journal of Allergy and Clinical Immunology

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“…The total monthly dose of SC Ig required to give the same "area under the curve" of serum IgG over time has been calculated at 1.37 to 1.53 times the dose of IV Ig [19][20][21][22][23], thus current package inserts for SC products recommend higher doses of Ig for subjects given SC forms. However, for this home care provider, the mean Ig dose was actually lower for patients receiving SC Ig (408.5 mg/kg/month) than it was for patients receiving IV Ig formulations (568.3 mg/kg/month), suggesting that common use in the U.S. has not reflected the higher doses suggested.…”

Section: Discussionmentioning

confidence: 99%

Home Care Use of Intravenous and Subcutaneous Immunoglobulin for Primary Immunodeficiency in the United States

Huang

Cunningham‐Rundles

2012

Journal of Allergy and Clinical Immunology

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Purpose-Utilization reports on immunoglobulin (Ig) use for immunodeficiency in the United States (U.S.) have focused on prescribing practices in hospitals. There have been no large-scale reports on Ig use for immune deficiency in the home. We investigated the use of Ig in 3,187 subjects diagnosed with primary immunodeficiency.Methods-Cross-sectional data on 4,580 subjects in the U.S. receiving Ig in 2011 was obtained from a major home care provider. Demographics, route, dose, and frequency of Ig use by subjects with ICD-9 coded primary immunodeficiencies were analyzed.Results-Of 4,580 subjects, 3,187 had ICD-9 codes suggesting primary immunodeficiencies; 1,939 (60.8 %) were females and 1,248 (39.2 %) were males, with age ranging from 0 to 95 years. The predominant diagnoses were: common variable immunodeficiency (279.06; n =1,764; 55.3 %), hypogammaglobulinemia (279.00; n=635; 19.9 %), unspecified immunity deficiency (279.3; n=286; 9 %), other selective Ig deficiencies (279.03; n=171; 5.4 %), and agammaglobulinemia (279.04; n=127; 4 %). 54 % of subjects received Ig by the subcutaneous (SC) route, and 46 % by intravenous (IV) route, with more SC use by older subjects. The mean dose prescribed was 483 mg/kg/month, but less Ig was ordered for subjects on SCIg (409 mg/kg/month), as compared to subjects on IVIg (568 mg/kg/month). A highly significant inverse correlation between increasing age and dosage of Ig ordered was found (P=<.0001).Conclusion-Analysis of home care use of Ig in primary immune deficiency revealed that the SC route was prescribed more than the IV route, especially for older patients. By either method of administration, less immunoglobulin was prescribed for older subjects.

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“…On the other hand, the American sources recommend to multiply the current dose with a coefficient which varies by the concentration of the product and which is derived from the area under the curve pharmacokinetically (x1.37 for 16% and 1.53 for 20%) (16). In our country, studies have recommended to use the coefficient 1.37 for the products with 10% concentration (19). In the practice of our clinic, the total monthly dose was established by using the same coefficient.…”

Section: Discussionmentioning

confidence: 99%

Use of subcutaneous immunoglobulin in primary immune deficiencies

et al. 2016

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Aim: Immunoglobulin replacement therapy is required to reduce the frequency and severity of infections in patients with primary antibody deficiencies. Immunoglobulin G (IgG) can be administered intramuscularly, intravenously or subcutaneously. We aimed to evaluate the efficacy, dose adjustment and adverse events in subcutaneous immunoglobulin therapy by retrospectively presenting the records of 16 patients who received subcutaneous immunoglobulin therapy. Material and Methods: The demographic findings, clinical and laboratory findings, subcutaneous immunoglobulin dosage and dose frequency, infusion time, area and methods, adverse events and frequency of infections were obtained from patient files and recorded. Results: Sixteen patients (seven female, nine male) aged between 0-33 years who were diagnosed with primary immune deficiency and treated with subcutaneous immunoglobulin were enrolled. All patients had been receiving intravenous imunoglobulin (5-10%) at a dose of 0.33-1.25 gr/ kg/dose with two-four week intervals before subcutaneous immunoglobulin. Subcutaneous immunoglobulin (10%) was administered at a dose of 0.03-0.43 gr/kg/dose with one-two week intervals. No significant difference was found between serum through IgG levels before administration of intravenous imunoglobulin and steady state IgG levels during subcutaneous immunoglobulin therapy. When five patients whose serum through IgG levels were below 600 mg/dL were evaluated, however, a significant increase was found in steady state IgG levels with subcutaneous immunoglobulin therapy (p=0.043). In a ten-month follow-up period, seven infections were observed in four patients (three upper respiratory infectons, two lower respiratory tract infections and three acute gastroenteritis). No acute severe bacterial infection was observed. Local advers reaction was reported in only 10 of 180 infusions (6%). No serious adverse events were reported. All 16 patients were willing to continue IgG replacement therapy by subcutaneous administration. Conclusions: Ig replacement therapy by subcutaneous route is an efficient, safe and easy option which is eligible for individual administration. Home therapy is feasible for patients with primary immune deficiency, if informed consent is obtained and sufficient education is ensured. (Turk Pediatri Ars 2016; 51: 8-14)

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Pharmacokinetics and safety of subcutaneous immune globulin (human), 10% caprylate/chromatography purified in patients with primary immunodeficiency disease

Cited by 66 publications

References 29 publications

Bioavailability of IgG Administered by the Subcutaneous Route

Bioavailability of IgG Administered by the Subcutaneous Route

Home Care Use of Intravenous and Subcutaneous Immunoglobulin for Primary Immunodeficiency in the United States

Use of subcutaneous immunoglobulin in primary immune deficiencies

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