Does Hepatic Impairment Affect the Exposure of Monoclonal Antibodies?
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
28
10
2019
accepted:
13
12
2019
pubmed:
4
1
2020
medline:
17
2
2021
entrez:
4
1
2020
Statut:
ppublish
Résumé
Limited information is available regarding the effect of hepatic impairment (HI) on the pharmacokinetics of monoclonal antibodies (mAbs). The results of an earlier report based on therapeutic proteins, including mAbs, approved through the end of 2012 were inconclusive due to limited HI data available at that time. New HI data for mAbs or antibody-drug conjugates (ADCs; with a focus on the mAb component) available between 2013 and 2018 were evaluated. The investigation indicates there is almost no data for severe HI, limited data for moderate HI, and abundant data for mild HI. A significant exposure decrease was found for several mAbs or ADCs and a trend for decreasing area under the concentration-time curve (AUC) was observed for other mAbs. Multiple potential mechanisms may contribute to the exposure decrease. Dose may need to be adjusted for patients with HI, after taking into account the exposure-response relationships for both efficacy and safety.
Substances chimiques
Antibodies, Monoclonal
0
Immunoconjugates
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1256-1262Informations de copyright
© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
Références
Ecker, D.M., Jones, S.D. & Levine, H.L. The therapeutic monoclonal antibody market. MAbs 7, 9-14 (2015).
US Food and Drug Administration. Guidance for industry:pharmacokinetics in patients with impaired hepatic function: study design, data analysis, and impact on dosing and labeling <https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072123.pdf> (May 2003). Accessed May 8, 2019.
Ryman, J. & Meibohm, B. Pharmacokinetics of monoclonal antibodies. CPT Pharmacometrics Syst. Pharmacol. 6, 576-588 (2017).
Yang, J., Shord, S., Zhao, H., Men, Y. & Rahman, A. Are hepatic impairment studies necessary for therapeutic proteins? Clin. Ther. 35, 1444-1451 (2013).
Kadcyla [prescribing information] (Genentech, South San Francisco, CA, 2018) <https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125427s104lbl.pdf>. Accessed May 8, 2019.
Repatha [prescribing information] (Amgen, Thousand Oaks, CA, 2019) <https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125522s022lbl.pdf>. Accessed May 8, 2019.
Zhao, B. et al. Brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive heaematologic malignancies and hepatic or renal impairment. Br. J. Clin. Pharmacol. 82, 696-705 (2016).
Adcetris [prescribing information] (Seattle Genetics, Bothell, WA, 2018) <https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/125388s099lbl.pdf>. Accessed May 8, 2019.
Center for Drug Evaluation and Research. Clinical pharmacology review [alirocumab injection] <https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/125559Orig1s000ClinPharmR.pdf> (2014). Accessed May 8, 2019.
Center for Drug Evaluation and Research. Clinical pharmacology review [bezlotoxumab] <https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761046Orig1s000ClinPharmR.pdf> (2015). Accessed May 8, 2019.
Center for Drug Evaluation and Research. Multi-discipline review [mogamulizumab] <https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/761051Orig1s000MultidisciplineR.pdf> (2017). Accessed May 8, 2019.
Center for Drug Evaluation and Research. Clinical pharmacology review [trastuzumab emtansine] <https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125427Orig1s000ClinPharmR.pdf> (2012). Accessed May 8, 2019.
Center for Drug Evaluation and Research. Clinical pharmacology review [bilimumab] <https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/125370Orig1s000ClinPharmR.pdf> (2009). Accessed May 8, 2019.
Center for Drug Evaluation and Research. Clinical pharmacology review [gemtuzumab ozogamicin] <https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761060Orig1s000Orig1Orig2s000ClinPharmR.pdf> (2016). Accessed May 8, 2019.
Fasanmade, A.A. et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur. J. Clin. Pharmacol. 65, 1211-1228 (2009).
Cosson, V.F., Ng, V.W., Lehle, M. & Lum, B.L. Population pharmacokinetics and exposure-response analyses of trastuzumab in patients with advanced gastric or gastroesophageal junction cancer. Cancer Chemother. Pharmacol. 73, 737-747 (2014).
Gibbs, J. et al. Evaluation of evolocumab (AMG 145), a fully human anti-PCSK9 IgG2 monoclonal antibody, in subjects with hepatic impairment. J. Clin. Pharmacol. 57, 513-523 (2017).
Li, C. et al. A phase I pharmacokinetic study of trastuzumab emtansine (T-DM1) in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer and normal or reduced hepatic function. Clin. Pharmacokinet. 56, 1069-1080 (2017).
Wang, J. et al. Exposure-response relationship of T-DM1: insight into dose optimization for patients with HER2-positive metastatic breast cancer. Clin. Pharmacol. Ther. 95, 558-564 (2014).
Westergaard, H., Jarnum, S., Ramsöe, K. & Ranek, L. Albumin and immunoglobulin turnover in patients with chronic active liver disease treated with prednisone. Scand J. Gastroenterol. 7, 623-30 (1972).
Liu, W.T. et al. The injured liver induces hyperimmunoglobulinemia by failing to dispose of antigens and endotoxins in the portal system. PLoS One 10, e0122739 (2015).
Fallatah, H.I. & Akbar, H.O. Elevated serum immunoglobulin G levels in patients with chronic liver disease in comparison to patients with autoimmune hepatitis. Libyan J. Med. 5, 4857-4860 (2010).
Morell, A., Terry, W.D. & Waldmann, T.A. Metabolic properties of IgG subclasses in man. J. Clin. Invest. 49, 673-680 (1970).
Li, L., Gardner, I., Dostalek, M. & Jamei, M. Simulation of monoclonal antibody pharmacokinetics in humans using a minimal physiologically based model. AAPS J. 16, 1097-1109 (2014).
Karagiannis, P. et al. Elevated IgG4 in patient circulation is associated with the risk of disease progression in melanoma. Oncoimmunology 4, e1032492 (2015).
Upton, J. Immunodeficiencies with hypergammaglobulinemia: a review. LymphoSign J. 2, 57-73 (2015).
Dostálová, O., Wagnerová, V., Schön, E., Wagner, V. & Jelínek, J. Serum immunoglobulin levels in cancer patients. III. Immunoglobulin levels and metastases of malignant tumors. Neoplasma 24, 177-191 (1977).
Disibio, G. & French, S.W. Metastatic patterns of cancers: results from a large autopsy study. Arch. Pathol. Lab. Med. 132, 931-939 (2008).
Nazario, H.E., Lepe, R. & Trotter, J.F. Metastatic breast cancer presenting as acute liver failure. Gastroenterol. Hepatol. (N.Y.) 7, 65-66 (2011).
Min, B.S., Kim, N.K., Jeong, H.C. & Chung, H.C. High levels of serum VEGF and TIMP-1 are correlated with colon cancer liver metastasis and intrahepatic recurrence after liver resection. Oncol. Lett. 4, 123-130 (2012).
Brandsma, A.M., Jacobino, S.R., Meyer, S., ten Broeke, T. & Leusen, J.H. Fc receptor inside-out signaling and possible impact on antibody therapy. Immunol. Rev. 268, 74-87 (2015).
Mannaa, F.A. & Abdel-Wahhab, K.G. Physiological potential of cytokines and liver damages. Hepatoma Res. 2, 131-143 (2016).
Vidarsson, G., Dekkers, G. & Rispens, T. IgG subclasses and allotypes: from structure to effector functions. Front. Immunol. 5, 520 (2014).