Background/Purpose: Women with chronic inflammatory diseases, including rheumatic diseases and Crohn’s disease (CD), face uncertainty regarding the safety of the use of biologics during breastfeeding. For women with RA, postpartum flare is common.¹ Currently, limited and non-validated data exist on potential transfer of anti-TNFs into breast milk. CRADLE was the first sponsored study designed to evaluate certolizumab pegol (CZP) concentrations in breast milk, and to estimate average daily infant dose of maternal CZP (the daily amount of CZP potentially ingested by infants).

Methods: CRADLE (NCT02154425) was a safety and pharmacokinetic study of lactating mothers (≥6 weeks postpartum) receiving commercial CZP for an approved indication. Decision to treat with CZP and to breastfeed was made independently of study participation. At steady-state (≥3 CZP doses), breast milk samples were collected at days 0, 2, 4, 6, 8, 10, 12, 14 (±28) from each mother across 1 dosing period (14 days for 200 mg Q2W; 28 days for 400 mg Q4W). Maternal burden was minimized through in-home visits with nurses. A highly sensitive CZP-specific ELISA was developed (validated in milk; LLQ=0.032 μg/mL, 10-fold lower than assay used in CZP pharmacokinetic studies²). CZP stability in milk was confirmed.

Results: 18 CZP-treated mothers were screened and 17 entered the sampling period; 16 on 200 mg Q2W; 1 on 400 mg Q4W (7 RA; 5 SpA; 5 CD; Table A). Samples from 4/17 mothers had no measurable CZP in breast milk; 13/17 had quantifiable levels at any time point (highest concentration: 0.076 μg/mL; Table B). Estimated average daily infant dose ranged 0–0.0104 mg/kg/day; median relative infant dose (calculated³ post hoc by Dr Hale): 0.15%. The infants of mothers exposed to CZP had a safety profile consisting of events occurring in unexposed infants of similar age (Table C).

Conclusion: Using the highly sensitive assay, CZP was undetectable in 56% of milk samples collected. When detectable, CZP concentrations were less than 3 times LLQ (<1% of expected plasma concentration of a therapeutic dose),² indicating no to minimal transfer of CZP from plasma to breast milk. Relative infant dose was below 0.5% of maternal dose; <10% is considered unlikely to be of clinical concern.³ In addition, CZP absorption by infants via breast milk is unlikely due to its Fc-free molecular structure⁴ and the low bioavailability of biologics after oral administration. These findings are reassuring and imply that continuation of CZP treatment is compatible with breastfeeding. References: 1. de Man Y. Arthritis Rheum 2008;59:1241–8; 2. Lacroix B. Gastroenterol 2010;138:S163–4; 3. Bennett P. Drugs and Human Lactation. 1996; 4. Israel E. Immunology 1997;92:69–74. [Resubmission from ACG 2016] Funding: UCB Pharma. We are indebted to the mothers and their infants for their altruistic participation. We thank the nurses, investigator teams, and Nicole Hurst (PPD) and acknowledge Amanda Golembesky and Gerry Parker, UCB Pharma.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluating-transfer-of-certolizumab-pegol-into-breast-milk-results-from-a-prospective-postmarketing-multicenter-pharmacokinetic-study/