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Steady-State Serum IgG Trough Levels Are Adequate for Pharmacokinetic Assessment in Patients with Immunodeficiencies Receiving Subcutaneous Immune Globulin.

ABSTRACT: Patients with primary immunodeficiency diseases often require lifelong immunoglobulin (IG) therapy. Most clinical trials investigating IG therapies characterize serum immunoglobulin G (IgG) pharmacokinetic (PK) profiles by serially assessing serum IgG levels. This retrospective analysis evaluated whether steady-state serum IgG trough level measurement alone is adequate for PK assessment. Based on individual patient serum IgG trough levels from two pivotal trials (phase 2/3 European [NCT01412385] and North American [NCT01218438]) of weekly 20% subcutaneous IG (SCIG; Cuvitru, Ig20Gly), trough level-predicted IgG AUC (AUC_τ,tp) were calculated and compared with the reported AUC calculated from serum IgG concentration-time profiles (AUC_τ). In both studies, mean AUC_τ,tp values for Ig20Gly were essentially equivalent to AUC_τ with point estimates of geometric mean ratio (GMR) of AUC_τ,tp/AUC_τ near 1.0 and 90% CIs within 0.80-1.25. In contrast, for IVIG, 10%, mean AUC_τ,tp values were lower than AUC_τ by >20%, (GMR [90% CI]: 0.74 [0.70-0.78] and 0.77 [0.73-0.81] for the two studies, respectively). Mean AUC_τ,tp values calculated for 4 other SCIG products (based on mean IgG trough levels reported in the literature/labels) were also essentially equivalent to the reported AUC_τ (differences <10% for all except HyQvia, a facilitated SCIG product), while differences for IVIG products were >20%. In conclusion, steady-state serum IgG levels following weekly SCIG remain stable, allowing for reliable prediction of AUC over the dosing interval using trough IgG levels. These findings indicate that measuring steady-state serum IgG trough levels alone may be adequate for PK assessment of weekly SCIG.

SUBMITTER: Li Z

PROVIDER: S-EPMC8310849 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn the past, impurities in vancomycin formulations were thought to contribute to nephrotoxicity. In contrast, when current, purer formulations are dosed at conventional trough levels (i.e., 5-15 mg/L), the incidence of nephrotoxicity is relatively low. Recent guidelines have recommended targeting higher vancomycin trough levels in treatment of complicated methicillin-resistant Staphylococcus aureus infections. Dosing based on these higher trough levels may be associated with nephrotoxicity, so the potential risk factors for vancomycin-associated nephrotoxicity require clearer definition.ObjectivesTo determine the occurrence of nephrotoxicity in patients receiving more than 7 days of vancomycin therapy with high trough levels (15-20 mg/L) and to identify and evaluate specific risk factors related to development of vancomycin-associated nephrotoxicity (i.e., serum creatinine ? 44.2 ?mol/L or increase ? 50% [i.e., ? 26.2 ?mol/L] from baseline on 2 consecutive days).MethodsHealth care records were reviewed for patients seen at 2 major teaching hospitals between January 2008 and March 2011. Patients who had attained high trough levels of vancomycin were screened for eligibility. Patients with unstable renal function, those undergoing hemodialysis, and those for whom dosage and/or sampling times were unclear were excluded. Univariate and multivariate analyses were performed to identify risk factors associated with nephrotoxicity. Univariate variables with p < 0.1 were included in the logistic regression model.ResultsOf the 176 patients with high trough levels included in the analysis, 24 (14%) experienced nephrotoxicity. In univariate analysis, admission to a general medicine unit (the setting of care for 16 [67%] of the 24 patients with nephrotoxicity) and extended duration of vancomycin treatment were identified as risk factors for nephrotoxicity (p < 0.1). Other risk factors included gastrointestinal comorbidity (p = 0.056), malignancy (p = 0.044), and febrile neutropenia (p = 0.032). Multivariate analysis identified treatment on general medicine units and treatment courses longer than 7 days as independent predictors of vancomycin-associated nephrotoxicity.ConclusionPatients being treated on general medicine units and those receiving vancomycin for more than 7 days had an increased likelihood of experiencing nephrotoxicity. The increased risk for patients on general medicine units is likely multifactorial. The relationship between treatment duration and risk of nephrotoxicity appeared to be linear. When using extended-duration, high-trough vancomycin therapy, clinicians should be vigilant in monitoring for nephrotoxicity.

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Steady-State Serum IgG Trough Levels Are Adequate for Pharmacokinetic Assessment in Patients with Immunodeficiencies Receiving Subcutaneous Immune Globulin.

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