Privigen® has similar pharmacokinetic properties in primary and secondary immune deficiency

Tortorici, Michael A.; Lawo, John‐Philip; Weide, Rudolf; Jochems, Jeanine; Puli, Shilpa; Hofmann, Jutta; Pfruender, Dietmar; Rojavin, Mikhail

doi:10.1016/j.intimp.2018.11.008

Cited by 6 publications

(8 citation statements)

References 44 publications

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“…The current analysis also demonstrated that the PPK estimates of this analysis were consistent with the estimates reported in the previous PPK model, thus validating the original PPK model. 25,26,28 Goodness-of-fit plots revealed that the final model is consistent with the observed data, and the pcVPC confirmed that the final IgG PPK model provided a good description of the data. IgG endo level was fixed to 4.0 g/L in this analysis due to the lack of data on IgG levels before treatment.…”

Section: Discussionsupporting

confidence: 60%

Pharmacometric Analysis of IgPro10 in Japanese and Non-Japanese Patients With Primary Immunodeficiency

Luo

Baheti

Tortorici

et al. 2020

Clinical Therapeutics

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Purpose: Immunoglobulin (Ig) G replacement therapy, administered intravenously (IVIG) or subcutaneously (SCIG), is the standard treatment in patients with primary immunodeficiencies (PID). We aimed to characterize the pharmacokinetic (PK) characteristics of serum IgG following administration of IgPro10 every 3 or 4 weeks in Japanese patients with PID, and compare with PK in non-Japanese patients. A previously developed population PK (PPK) model was validated, and predicted parameters were compared with the results from the clinical study. Methods: The previously developed PPK model, containing IgG concentration data from 5 non-Japanese studies, was supplemented with data from 3 Japanese studies of IgPro10 or IgPro20 to compare the IgG PK parameters between Japanese and non-Japanese patients. The model was externally validated by simulating IgG concentrationetime profiles in Japanese patients to predict serum IgG PK characteristics and to compare them with observed Japanese PK data from Study IgPro10_3004. Findings: The analysis included 4502 serum IgG concentration values (from 34 Japanese and 168 non-Japanese patients). PPK estimates from the current analysis demonstrated a clearance (CL) of 0.139 L/d, central volume (V2) of 4.01 L, inter-compartmental clearance (Q) of 0.30 L/d, and peripheral volume of 3.51 L. These results were consistent with those from the previously published PPK model, with similar bootstrap means and 95% CIs. Goodness-of-fit criteria indicated that the final PPK model was consistent with observed data, with no systemic bias in model prediction. Prediction-corrected visual predictive checks confirmed a good description of data on both SCIG and IVIG. PK parameters were equivalent between Japanese and non-Japanese patients. Body weight was determined to be a significant covariate on both CL and V2. Simulated and observed AUC and maximum and minimum serum IgG concentrations were similar, with 90% CIs overlapping between simulated and observed IgG concentrations in Japanese patients. Implications: PK parameter estimates of serum IgG were similar between Japanese and non-Japanese patients with PID. The PPK model, updated with Japanese data, was consistent with the previously published PPK model and could accurately predict both individual and population serum IgG concentrationetime profiles following IgPro10 IV infusions every 3 or 4 weeks. EudraCT identifier: 2016-001631-12.

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Section: Discussionsupporting

confidence: 60%

Pharmacometric Analysis of IgPro10 in Japanese and Non-Japanese Patients With Primary Immunodeficiency

Luo

Baheti

Tortorici

et al. 2020

Clinical Therapeutics

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“…However, the addition of weight itself tremendously reduced the variability of Vd and CL of the drug. This is consistent with previous population PK studies, which have identified weight as a covariate to their model 26–29 . The previous analyses did not investigate the impact of other possible covariates on the PK of IgG therapy.…”

Section: Discussionsupporting

confidence: 88%

“…Weight was found to be an important covariate for both Vd and CL. This was in contrast with other population PK studies where they described the PK of IgG therapy as a two‐compartment model with first‐order absorption and linear elimination 24,26,27,29,43 . The data from these five population PK studies were obtained from similar phase 3 clinical trials evaluating IgG therapy in patients with PID.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetic modelling of intravenous immunoglobulin in patients with predominantly antibody deficiencies

Lee

Saffian

Makmor‐Bakry

et al. 2021

Brit J Clinical Pharma

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Aims There is considerable interpatient variability in the pharmacokinetics (PK) of intravenous immunoglobulin G (IVIG), causing difficulty in optimizing individual dosage regimen. This study aims to estimate the population PK parameters of IVIG and to investigate the impact of genetic polymorphism of the FcRn gene and clinical variability on the PK of IVIG in patients with predominantly antibody deficiencies. Methods Patients were recruited from four hospitals. Clinical data were recorded and blood samples were taken for PK and genetic studies. Population PK parameters were estimated by nonlinear mixed‐effects modelling in Monolix®. Models were evaluated using the difference in objective function value, goodness‐of‐fit plots, visual predictive check and bootstrap analysis. Monte Carlo simulation was conducted to evaluate different dosing regimens for IVIG. Results A total of 30 blood samples were analysed from 10 patients. The immunoglobulin G concentration data were best described by a one‐compartment model with linear elimination. The final model included both volume of distribution (Vd) and clearance (CL) based on patient's individual weight. Goodness‐of‐fit plots indicated that the model fit the data adequately, with minor model mis‐specification. Genetic polymorphism of the FcRn gene and the presence of bronchiectasis did not affect the PK of IVIG. Simulation showed that 3–4‐weekly dosing intervals were sufficient to maintain IgG levels of 5 g L−1, with more frequent intervals needed to achieve higher trough levels. Conclusions Body weight significantly affects the PK parameters of IVIG. Genetic and other clinical factors investigated did not affect the disposition of IVIG.

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“…The first dose was administered at least 12 days beforehand, with the benefit of IVIg peaking around 15 days, just when surgery took place. [28][29][30][31] Patients assigned to the placebo group received intravenous saline solution for the same time period and under the same conditions. The medications were provided by the pharmacy department in photoprotective bags and opaque tubes to mask the vials of immunoglobulin and placebo.…”

Section: Study Proceduresmentioning

confidence: 99%

Intravenous immunoglobulin to prevent myasthenic crisis after thymectomy and other procedures can be omitted in patients with well-controlled myasthenia gravis

Gamez

Salvadó

Carmona

et al. 2019

Ther Adv Neurol Disord

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Background: Myasthenic crisis (MC) is a potentially life-threatening complication of myasthenia gravis. Its precipitating factors include surgical procedures, particularly thymectomy. The role of preoperative intravenous immunoglobulin (IVIg) in preventing MC in patients scheduled for thymectomy and other surgery with general anaesthesia is unknown. Our objective was to test the hypothesis that preoperative IVIg is effective in preventing myasthenic crisis in patients with myasthenia gravis scheduled for surgery under general anaesthesia, including thymectomy. Methods: A prospective, randomized, double-blind, single-centre study was conducted over a 4-year period. The treatment group received IVIg, 0.4 g/kg/day preoperatively for 5 consecutive days, and the placebo group received saline solution under the same conditions. The two groups were age-matched, with similar functional status, and Myasthenia Gravis Foundation of America class. All patients had well-controlled myasthenia gravis with minimal manifestations before surgery. The primary outcome measured was MC. Intubation times, time in the recovery room, number of postoperative complications, and days of hospitalization were the secondary outcomes measured. Results: A total of 47 patients were randomized, 25 to the IVIg group and 22 to placebo. There were 19 men and 28 women, with a mean age of 58.6 years, mean body mass index of 27.8 kg/m2, and mean acetylcholine receptor antibodies of 12.9 nmol/l. The mean forced vital capacity was 84.4%. The mean quantitative myasthenia gravis sum score was 6.3. Ten patients (five in each arm) had a history of MC. Thymectomy was performed in 16 patients. Only one patient in the placebo group presented with MC requiring non-invasive ventilation (but no reintubation) for 6 days. Neither differences between groups in the univariate analysis nor risk factors for MC in the multivariate analysis were found. Conclusions: Preoperative IVIg to prevent MC does not appear to be justified in well-controlled myasthenia gravis patients. This study provides class I evidence that preparation with IVIg to prevent MC is not necessary in well-controlled myasthenia gravis patients scheduled for surgery with general anaesthesia.

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Privigen® has similar pharmacokinetic properties in primary and secondary immune deficiency

Cited by 6 publications

References 44 publications

Pharmacometric Analysis of IgPro10 in Japanese and Non-Japanese Patients With Primary Immunodeficiency

Pharmacometric Analysis of IgPro10 in Japanese and Non-Japanese Patients With Primary Immunodeficiency

Population pharmacokinetic modelling of intravenous immunoglobulin in patients with predominantly antibody deficiencies

Intravenous immunoglobulin to prevent myasthenic crisis after thymectomy and other procedures can be omitted in patients with well-controlled myasthenia gravis

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