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Minimal neonatal transfer of certolizumab pegol in a Japanese patient with rheumatoid arthritis
  1. Takayoshi Morita1,
  2. Kosuke Fujimoto1,2,3,
  3. Yoshihito Shima1,
  4. Atsushi Ogata1,4,
  5. Atsushi Kumanogoh1
  1. 1 Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Osaka, Japan
  2. 2 Department of Mucosal Immunology, School of Medicine, Chiba University, Japan
  3. 3 Division of Innate Immune Regulation, Institute of Medical Science, International Research and Development Center for Mucosal Vaccines, The University of Tokyo, Japan
  4. 4 Division of Allergy, Rheumatology and Connective Tissue Disease, NTT West Osaka Hospital, Osaka, Japan
  1. Correspondence to Dr Atsushi Ogata, Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan;{at}

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Clowse et al 1 have reported minimal to no transfer of certolizumab pegol (CZP) into breast milk, and their findings have supported the continuation of CZP treatment during breast milk feeding. Rheumatoid arthritis (RA) often develops in women of childbearing age. It is generally difficult to treat these patients with methotrexate, which is the anchor drug for RA. Therefore, biologics, such as tumour necrosis factor (TNF) inhibitors, are often considered for active RA during pregnancy. However, the biologics cross the placenta from mother to fetus and transfer into breast milk during lactation. Although a meta-analysis report indicated that anti-TNF-α therapy did not increase the risks, such as congenital malformation or abortion during pregnancy, in patients with inflammatory bowel disease,2 there have been major concerns for the safety of biologics to the fetus. It is well known that the neonatal Fc receptor for IgG (FcRn) and the Fc portion of antibodies are important for placental transfer of biologics. Novel TNF inhibitor, CZP, lacks the Fc fragment, suggesting its limited transfer through the placenta.3 Current data on CZP exposure during pregnancy have suggested CZP safety and tolerability during pregnancy.4 5 Additionally, Clowse et al indicated CZP safety of breast milk feeding for infants. We conducted a similar examination in a Japanese patient. A 30-year-old Japanese woman with RA became pregnant. Before pregnancy, her disease activity was low with 5 mg of prednisolone (PRD) use. However, her symptoms got worse and disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) increased from 3.19 to 3.86 at 8 weeks of pregnancy. Following this, the PRD dose was increased to 10 mg, but PRD treatment could not control her disease activity. DAS28-ESR increased to 5.71 at 28 weeks of pregnancy. At this point, CZP treatment was started under the informed consent of the patient because CZP was considered not to pass through the placenta to the fetus. DAS28-ESR decreased to 3.58, and her symptoms improved. Her fetus showed normal development under CZP treatment. At 40 weeks of pregnancy, she delivered a healthy baby boy. We evaluated the concentration of CZP using ELISA (Sanquin, Amsterdam, Netherlands). Although the trough concentrations of CZP were well maintained during pregnancy (table 1), CZP was not detected in cord blood and neonatal serum on day three after birth. After delivery, she continued CZP therapy. Eight weeks after delivery, the CZP concentration in the mother’s serum was maintained. We evaluated the CZP concentration in breast milk at the same time. CZP was not detected in breast milk before or after CZP administration (table 1). We also confirmed CZP in sera and breast milk using western blot analysis. After electrophoresis, PEGylated proteins were detected by anti-PEG antibody (Abcam, clone PEG-B-47). The PEGylated proteins were detected in maternal serum but not in cord blood, foetal serum and breast milk (figure 1).

Table 1

Concentration of CZP in sera and breast milk

Figure 1

Certolizumab pegol, detected as a PEGyrated protein, was detected in maternal blood but not in cord blood, neonatal blood and breast milk.

Our case supports the hypothesis that the unique structure of CZP limits its transfer to the fetus and breast milk. It provides the possibility of CZP treatment for RA during late gestation and breast milk feeding without potential harm to the newborn.



  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The ethics committee approval was obtained from our hospital’s ethics committee (Medical Center for Translational and Clinical Research) (authorisation code: 11122-2).

  • Provenance and peer review Not commissioned; internally peer reviewed.

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