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

J Clin Immunol. 2021 Aug;41(6):1331-1338. doi: 10.1007/s10875-021-00990-z. Epub 2021 May 26.


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 (AUCτ,tp) were calculated and compared with the reported AUC calculated from serum IgG concentration-time profiles (AUCτ). In both studies, mean AUCτ,tp values for Ig20Gly were essentially equivalent to AUCτ with point estimates of geometric mean ratio (GMR) of AUCτ,tp/AUCτ near 1.0 and 90% CIs within 0.80-1.25. In contrast, for IVIG, 10%, mean AUCτ,tp values were lower than AUCτ by >20%, (GMR [90% CI]: 0.74 [0.70-0.78] and 0.77 [0.73-0.81] for the two studies, respectively). Mean AUCτ,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 AUCτ (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.

Keywords: Cuvitru; Pharmacokinetics; intravenous immunoglobulin; primary immunodeficiency diseases; subcutaneous immunoglobulin.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Humans
  • Immunoglobulin G / blood*
  • Immunoglobulin G / therapeutic use*
  • Immunoglobulins, Intravenous / pharmacokinetics*
  • Immunologic Deficiency Syndromes / blood*
  • Immunologic Deficiency Syndromes / drug therapy*
  • Multicenter Studies as Topic
  • Primary Immunodeficiency Diseases / blood
  • Primary Immunodeficiency Diseases / drug therapy
  • Prospective Studies
  • Retrospective Studies


  • Immunoglobulin G
  • Immunoglobulins, Intravenous

Associated data