TABLE 3

Selected studies that evaluated subcutaneous absorption of monoclonal antibodies and Fc-fusion proteins using population analysis

DrugPopulationPopulation Mean F, %Population Mean ka, Day 1Between Subject Variability for ka, CV%Covariates for kaReferences
AdalimumabRheumatoid arthritis58Value not reportedVelagapudi et al., 2005
AMG317, fully human IgG2Healthy humans24.30.185Age (centered at 40 yr)Kakkar et al., 2011
−0.72b
CanakinumabHuman healthy and patients63.3 or 70.0a0.299 or 0.269a64Age (centered at 34 yr)Chakraborty et al., 2012
−0.555b
CanakinumabGouty arthritis58.8–73.5a0.193–0.296a50.8Age (centered at 52 yr)Chakraborty et al., 2013
−0.319b
DenosumabPostmenopausal women with osteopenia or osteoporosis63.80.21263Age (centered at 64 yr)Sutjandra et al., 2011
−0.577b
DenosumabBone metastasis61.20.25751.5Age (centered at 54 yr)Gibiansky et al., 2012
−0.509b
EfalizumabPsoriasis56.40.242Ng et al., 2005
EfalizumabPsoriasisc0.1910 fixedSun et al., 2005
EtanerceptJuvenile rheumatoid arthritis58c1.2215Yim et al., 2005
EtanerceptRheumatoid arthritisc0.79724.3 (73.1d)Lee et al., 2003
EtanerceptPsoriasisc0.754Nestorov et al., 2004
Fc-osteoprotegerinHealthy postmenopausal women7.190.314Zierhut et al., 2008
GolimumabPsoriatic arthritisc0.908Xu et al., 2009
GolimumabRheumatoid arthritisc0.125Hu et al., 2011
GolimumabAnkylosing spondylitisc1.01078.6Xu et al., 2010b
IgG subcutaneousPrimary immunodeficiency66.00.439Landersdorfer et al., 2013
MTRX1011A, humanized IgG1Rheumatoid arthritis52.3 (IIV 18.9 CV%)0.21268.7Zheng et al., 2011
OmalizumabAsthma62c0.48039.9Hayashi et al., 2007
OmalizumabAsthma0.458141Lowe et al., 2009
RomiplostimHealthy subjects49.90.610Wang et al., 2010
SirukumabHealthy subjectsc0.7760.0Zhuang et al., 2013
TNFR-Fc fusion proteinAnkylosing spondylitisc1.452 (Tlag = 1 h)55.6 (81.8 for Tlag)Fang et al., 2010
UstekinumabPsoriasisc0.3540 fixedZhu et al., 2009
UstekinumabPsoriatic arthritisc0.42782.4Zhu et al., 2010
  • F, systemic bioavailability; IIV, inter-individual variability; ka, first-order absorption rate constant; TNF, tumor necrosis factor.

  • a Depending on the drug product.

  • b Exponent for power model on centered covariate.

  • c Bioavailability was not modeled as a separate parameter; volume of distribution (Vd/F) and clearance (CL/F) were estimated. If the bioavailability value was reported, it was taken from previous studies.

  • d CV% for interoccasion variability.