Certolizumab pegol does not bind the neonatal Fc receptor (FcRn): Consequences for FcRn-mediated in vitro transcytosis and ex vivo human placental transfer

Journal of Reproductive Immunology

Volumn 116, Issue , 2016, Pages 7-12

  Porter, Charlene ^a   Armstrong Fisher, Sylvia ^b,c   Kopotsha, Tim ^d   Smith, Bryan ^d   Baker, Terry ^d   Kevorkian, Lara ^d   Nesbitt, Andrew ^d  

^a NHS GRAMPIAN   (United Kingdom)

^b UNIVERSITY OF ABERDEEN   (United Kingdom)

^c SCOTTISH NATIONAL BLOOD TRANSFUSION SERVICE   (United Kingdom)

^d UCB PHARMA   (Belgium)

Author keywords

Anti TNF; Certolizumab pegol; Fc receptor; Immunoglobulin transport; Materno fetal transfer

Indexed keywords

ADALIMUMAB; CERTOLIZUMAB PEGOL; ETANERCEPT; FC RECEPTOR; INFLIXIMAB; RHESUS D ANTIBODY; FC RECEPTOR, NEONATAL; HLA ANTIGEN CLASS 1; IMMUNOGLOBULIN G; PROTEIN BINDING; TUMOR NECROSIS FACTOR;

ARTERIAL CIRCULATION; ARTICLE; BINDING AFFINITY; BLOOD PH; COMPARATIVE STUDY; CONTROLLED STUDY; DISSOCIATION CONSTANT; EX VIVO STUDY; FEMALE; FETUS; FETUS CIRCULATION; FETUS WASTAGE; HUMAN; HUMAN TISSUE; IN VITRO STUDY; LIMIT OF QUANTITATION; PH; PLACENTA PERFUSION; PLACENTAL TRANSFER; PRIORITY JOURNAL; STEADY STATE; TRANSCYTOSIS; VENOUS RETURN; CELL CULTURE; IMMUNOLOGY; METABOLISM; ORGAN CULTURE TECHNIQUE; PLACENTA; PLACENTA CIRCULATION; PREGNANCY;

ADALIMUMAB; CELLS, CULTURED; CERTOLIZUMAB PEGOL; FEMALE; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IMMUNOGLOBULIN G; INFLIXIMAB; ORGAN CULTURE TECHNIQUES; PLACENTA; PLACENTAL CIRCULATION; PREGNANCY; PROTEIN BINDING; RECEPTORS, FC; TRANSCYTOSIS; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84964318482     PISSN: 01650378     EISSN: 18727603     Source Type: Journal    
DOI: 10.1016/j.jri.2016.04.284     Document Type: Article

References (35)

1. Ali Y.M., et al. Can tumor necrosis factor inhibitors be safely used in pregnancy?. J. Rheumatol. 2010, 37:9-17.
2. Armstrong-Fisher S.S., et al. Transfer of IgG1 and IgG3 subclasses from polyclonal and monoclonal anti-D during in vitro placental perfusions. Transfus. Med. 1997, 7:24.
3. Bourne T., et al. A PEGylated Fab' fragment against tumor necrosis factor for the treatment of Crohn disease: exploring a new mechanism of action. BioDrugs 2008, 22:331-337.
4. Bush M.C., et al. Perinatal outcomes in inflammatory bowel disease. J. Maternal-fetal Neonatal Med. 2004, 15:237-241.
5. Chaudhury C., et al. The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan. J. Exp. Med. 2003, 197:315-322.
6. Claypool S.M., et al. Functional reconstitution of human FcRn in Madin-Darby canine kidney cells requires co-expressed human beta 2-microglobulin. J. Biol. Chem. 2002, 277:28038-28050.
7. Claypool S.M., et al. Bidirectional transepithelial IgG transport by a strongly polarized basolateral membrane Fcgamma-receptor. Mol. Biol. Cell 2004, 15:1746-1759.
8. De Man Y.A., et al. Association of higher rheumatoid arthritis disease activity during pregnancy with lower birth weight: results of a national prospective study. Arthritis Rheum. 2009, 60:3196-3206.
9. Duncan J.I., et al. Transfer of immunoglobulin g across the isolated perfused human placental lobule. Reprod. Fertil. Dev. 1995, 7:1547-1550.
10. FDA, 2014. Cimzia (certolizumab pegol) prescribing information. Available at: (accessed 16.10.14.). http://www.Cimzia.Com/assets/pdf/prescribing_information.Pdf.
11. Fischer-Betz R.E., Schneider M. Biologics during pregnancy and breast-feeding. Z. Rheumatol. 2010, 69:780-787.
12. J. Flint. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-part i: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids Rheumatology (Oxford) 2016. 10.1093/rheumatology/kev404.
13. Ghetie V., et al. Increasing the serum persistence of an IgG fragment by random mutagenesis. Nat. Biotechnol. 1997, 15:637-640.
14. Gurbaxani B., et al. Are endosomal trafficking parameters better targets for improving mAb pharmacokinetics than FcRn binding affinity?. Mol. Immunol. 2013, 56:660-674.
15. James L.C., Tawfik D.S. The specificity of cross-reactivity: promiscuous antibody binding involves specific hydrogen bonds rather than nonspecific hydrophobic stickiness. Protein Sci. 2003, 12:2183-2193.
16. Junghans R.P., Anderson C.L. The protection receptor for IgG catabolism is the beta2-microglobulin-containing neonatal intestinal transport receptor. Proc. Natl. Acad. Sci. U. S. A. 1996, 93:5512-5516.
17. Mahadevan U., et al. The London position statement of the World Congress of Gastroenterology on biological therapy for IBD with the European Crohn's and Colitis Organisation: pregnancy and pediatrics. Am. J. Gastroenterol. 2011, 106:214-223. (quiz 224).
18. Mahadevan U., et al. PIANO: a 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy. Gastroenterology 2012, 142:S-149.
19. Mahadevan U., et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin. Gastroenterol. Hepatol. 2013, 11:286-292.
20. Marchioni R.M., Lichtenstein G.R. Tumor necrosis factor-alpha inhibitor therapy and fetal risk: a systematic literature review. World J. Gastroenterol.: WJG 2013, 19:2591-2602.
21. Morales M., et al. Crohn's disease as a risk factor for the outcome of pregnancy. Hepato-gastroenterology 2000, 47:1595-1598.
22. Nesbitt A., et al. Mechanism of action of certolizumab pegol (cdp870): in vitro comparison with other anti-tumor necrosis factor alpha agents. Inflamm. Bowel Dis. 2007, 13:1323-1332.
23. Ng S.W., Mahadevan U. Management of inflammatory bowel disease in pregnancy. Expert Rev. Clin. Immunol. 2013, 9:161-173. (quiz 174).
24. Norgard B., et al. Disease activity in pregnant women with Crohn's disease and birth outcomes: a regional Danish cohort study. Am. J. Gastroenterol. 2007, 102:1947-1954.
25. Ostensen M., Forger F. Management of RA medications in pregnant patients. Nat. Rev. Rheumatol. 2009, 5:382-390.
26. Raja H., et al. Safety of tumor necrosis factor inhibitors during pregnancy and breastfeeding. Transl. Vision Sci. Technol. 2012, 1:6.
27. Rivkin A. Certolizumab pegol for the management of Crohn's disease in adults. Clin. Ther. 2009, 31:1158-1176.
28. Roberts D.M., et al. Isolation and characterization of the Fc receptor from the fetal yolk sac of the rat. J. Cell Biol. 1990, 111:1867-1876.
29. Roopenian D.C., Akilesh S. FcRn: the neonatal Fc receptor comes of age. Nat. Rev. Immunol. 2007, 7:715-725.
30. Saji F., et al. Dynamics of immunoglobulins at the feto-maternal interface. Rev. Reprod. 1999, 4:81-89.
31. Simister N.E., Story C.M. Human placental Fc receptors and the transmission of antibodies from mother to fetus. J. Reprod. Immunol. 1997, 37:1-23.
32. Suzuki T., et al. Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: a comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR. J. Immunol. 2010, 184:1968-1976.
33. Urbaniak S.J., et al. Transfer of anti-D antibodies across the isolated perfused human placental lobule and inhibition by high-dose intravenous immunoglobulin: a possible mechanism of action. Br. J. Haematol. 1997, 96:186-193.
34. Weir N., et al. A new generation of high-affinity humanized PEGylated Fab' fragment anti-tumor necrosis factor-(alpha) monoclonal antibodies. Therapy 2006, 3:535-545.
35. Wiedmann M.W., et al. TNF alpha inhibition as treatment modality for certain rheumatologic and gastrointestinal diseases. Endocr. Metab. Immune Disord. Drug Targets 2009, 9:295-314.