Sara C LaHue1, Annika Anderson1, Kristen M Krysko1, Alice Rutatangwa1, Morna J Dorsey1, Thomas Hale1, Uma Mahadevan1, Elizabeth E Rogers1, Melissa G Rosenstein1, Riley Bove2. 1. From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA. 2. From the Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), School of Medicine, University of California San Francisco; Department of Neurology (S.C.L., A.A., K.M.K., A.R., R.B.), Weill Institute for Neurosciences, University of California San Francisco; Department of Pediatrics (M.J.D.), Division of Allergy, Immunology and Blood and Marrow Transplant, University of California San Francisco, CA; Department of Pediatrics (T.H.), Texas Tech University School of Medicine, Amarillo, TX; Department of Gastroenterology (U.M.), University of California San Francisco; Department of Pediatrics (E.E.R.), University of California San Francisco; and Department of Obstetrics (M.G.R.), Gynecology, and Reproductive Sciences, University of California San Francisco, CA. riley.bove@ucsf.edu.
Abstract
OBJECTIVE: To review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases. METHODS: We systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowledge of an additional article. These 30 studies were reviewed. These assessed the presence of our selected mAbs in human breastmilk in samples collected from a total of 155 individual women. RESULTS: Drug concentrations were typically low in breastmilk and tended to peak within 48 hours, although maximum levels could occur up to 14 days from infusion. Most studies did not evaluate the breastmilk to maternal serum drug concentration ratio, but in those evaluating this, the highest ratio was 1:20 for infliximab. Relative infant dose, a metric comparing the infant with maternal drug dose (<10% is generally considered safe), was evaluated for certolizumab (<1%), rituximab (<1%), and natalizumab (maximum of 5.3%; cumulative effects of monthly dosing are anticipated). Importantly, a total of 368 infants were followed for ≥6 months after exposure to breastmilk of mothers treated with mAbs; none experienced reported developmental delay or serious infections. CONCLUSIONS: The current data are reassuring for low mAb drug transfer to breastmilk, but further studies are needed, including of longer-term effects on infant immunity and childhood development.
OBJECTIVE: To review currently available data on the transfer of monoclonal antibodies (mAbs) in the breastmilk of women receiving treatment for neurologic and non-neurologic diseases. METHODS: We systematically searched the medical literature for studies referring to 19 selected mAb therapies frequently used in neurologic conditions and "breastmilk," "breast milk," "breastfeeding," or "lactation." From an initial list of 288 unique references, 29 distinct full-text studies met the eligibility criteria. One additional study was added after the literature search based on expert knowledge of an additional article. These 30 studies were reviewed. These assessed the presence of our selected mAbs in human breastmilk in samples collected from a total of 155 individual women. RESULTS: Drug concentrations were typically low in breastmilk and tended to peak within 48 hours, although maximum levels could occur up to 14 days from infusion. Most studies did not evaluate the breastmilk to maternal serum drug concentration ratio, but in those evaluating this, the highest ratio was 1:20 for infliximab. Relative infant dose, a metric comparing the infant with maternal drug dose (<10% is generally considered safe), was evaluated for certolizumab (<1%), rituximab (<1%), and natalizumab (maximum of 5.3%; cumulative effects of monthly dosing are anticipated). Importantly, a total of 368 infants were followed for ≥6 months after exposure to breastmilk of mothers treated with mAbs; none experienced reported developmental delay or serious infections. CONCLUSIONS: The current data are reassuring for low mAb drug transfer to breastmilk, but further studies are needed, including of longer-term effects on infant immunity and childhood development.
Authors: Bridget LaMonica Ostrem; Annika Anderson; Sarah Conway; Brian C Healy; Jiwon Oh; Dina Jacobs; Ruth Dobson; Edith Larmon Graham; A Dessa Sadovnick; Vanessa Zimmerman; Yanqing Liu; Riley Bove; Maria Houtchens Journal: Mult Scler J Exp Transl Clin Date: 2022-06-15
Authors: 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 Journal: Clin Pharmacokinet Date: 2021-02-05 Impact factor: 6.447