Vedolizumab Concentrations in Breast Milk: Results from a Prospective, Postmarketing, Milk-Only Lactation Study in Nursing Mothers with Inflammatory Bowel Disease

Wan Sun, Blair Fennimore, Dawn B Beaulieu, Razvan Arsenescu, Adam C Stein, Jingjing Chen, Tiffany Lin, Sonya McKnight, Harisha Kadali, Maria Rosario, Richard A Lirio, Wan Sun, Blair Fennimore, Dawn B Beaulieu, Razvan Arsenescu, Adam C Stein, Jingjing Chen, Tiffany Lin, Sonya McKnight, Harisha Kadali, Maria Rosario, Richard A Lirio

Abstract

Background and objectives: The safety of inflammatory bowel disease medications during lactation is of significant relevance to women of childbearing potential. Available data regarding the transfer of biologic agents for inflammatory bowel disease via breast milk are limited to case reports. The objective of this prospective postmarketing lactation study was to assess vedolizumab concentrations in breast milk from lactating vedolizumab-treated women with inflammatory bowel disease.

Methods: Breast milk was serially collected throughout the dosing interval from 11 patients receiving established intravenous vedolizumab 300-mg maintenance therapy every 8, 6, or 4 weeks. Maternal safety was also assessed.

Results: Vedolizumab was detectable in ~90% of milk samples collected from all patients. Following the day 1 dose, vedolizumab milk concentrations increased with a median of 3-4 days to peak concentration, and subsequently decreased exponentially. For the nine patients receiving vedolizumab every 8 weeks, the average relative infant dose was 20.9%. Using a mean trough serum concentration of 11.2 µg/mL from historical studies, the ratio of mean vedolizumab milk-to-serum concentration was ~ 0.4 to 2.2%, consistent with published data on vedolizumab and other monoclonal antibody therapeutics for inflammatory bowel disease. The maternal safety profile was similar to that observed in previous vedolizumab studies. Published vedolizumab studies also showed no adverse findings for infants breastfed by vedolizumab-treated mothers.

Conclusions: Vedolizumab was present in human breast milk at a low level. The decision to use vedolizumab should balance the benefit of therapy to the mother and the potential risks to the infant.

Trial registration: ClinicalTrials.gov, NCT02559713; registered 24 September, 2015.

Conflict of interest statement

Jingjing Chen, Sonya McKnight, Harisha Kadali, and Richard A. Lirio are Takeda employees and hold Takeda stock or stock options. Blair Fennimore has no conflicts of interest that are directly relevant to the content of this article. Dawn B. Beaulieu reports consulting fees from Takeda and AbbVie. Razvan Arsenescu reports consulting and speaker fees from Takeda. Adam C. Stein reports consulting and speaker fees from AbbVie and speaking fees from Pfizer. Tiffany Lin is contracted by Takeda via Certara. Wan Sun and Maria Rosario were Takeda employees at the time this research was conducted, and Maria Rosario reports granted patents and pending patent applications relating to the clinical pharmacology of vedolizumab.

Figures

Fig. 1
Fig. 1
Mean ± standard deviation vedolizumab milk concentrations over time by regimen following an infusion of intravenous vedolizumab at 300 mg (a: linear; b: semi-log). Frequency of dosing: Q4W every 4 weeks, Q6W every 6 weeks, Q8W every 8 weeks

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Source: PubMed

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