Abstract
Purpose :
To measure the levels of VEGF-A and ranibizumab or aflibercept in the breast milk of nursing women after receiving intravitreal anti-VEGF therapy.
Methods :
This is a prospective, multi-center study performed at St. Michael’s Hospital and Calgary Retina Consultants, Canada. Three nursing women were started on treatment with intravitreal anti-VEGF agents: patients 1 and 2 received treatment with ranibizumab for myopic choroidal neovascularization and patient 3 received aflibercept for diabetic macular edema. Breast milk samples from patients 1 and 2 were collected 1 hour before the first injection and at days 1-7, 14, 21, and 28 after the injection. Samples from patient 3 could only be collected until day 6 due to the lack of production of more breast milk. VEGF-A concentrations were determined using an immunoassay (R&D Systems Kit LXSAHM-01) with the Luminex platform. Ranibizumab and aflibercept levels were measured by ELISA using a kit for detection of ranibizumab (Alpha Diagnostic Intl. Inc.) or aflibercept (Eagle Biosciences, Inc.).
Results :
The following data correspond to the results encountered for patient 1: Ranibizumab levels were not detected in the breast milk at baseline, days 1 and 2. Ranibizumab was detected at day 3 (34.7ng/ml), with generally increasing levels over time: day 4 50.3ng/ml, day 5 53.2ng/ml, day 6 52.1ng/ml, day 7 38.6ng/ml, day 14 75.1ng/ml, day 21 121.1ng/ml, day 28 128.9ng/ml. VEGF-A was significantly suppressed at day 1 compared to baseline and demonstrated a reduction over time: baseline 22.8ng/ml, day 1 12.3ng/ml, day 2 7.1ng/ml, day 3 7.2ng/ml, day 4 6.1ng/ml, day 5 5.9ng/ml, day 6 5.4ng/ml, day 7 6.4ng/ml, day 14 2.2ng/ml, day 21 3.2ng/ml, day 28 4.9ng/ml. Data related to patients 2 and 3 are currently under analysis and will be added to the results.
Conclusions :
Ranibizumab does pass into human breast milk following an intravitreal injection and, during the same period, VEGF-A concentrations in the human milk decline with significant reduction detected by day 1. Based on our data, intravitreal ranibizumab treatment in nursing women raises a concern of possible adverse events in the developing infant. Further data from this study will show whether aflibercept also passes into the breast milk. This data is important to consider when counseling nursing women who develop diseases requiring anti-VEGF injections.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.