Rituximab Appears Safe for Women to Use While Breastfeeding, Small Study Finds
Results suggest that women with RRMS can continue with a disease-modifying treatment while breastfeeding.
The study “Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions” was published in the journal Neurology: Neuroimmunology & Neuroinflammation.
The therapy is a monoclonal antibody that works by targeting the CD20 protein found on the surface of immune cells called B-cells, which are known to contribute to myelin damage, the hallmark of MS (myelin is the protective coat of nerve cells that is damaged in MS). Rituximab is used off-label with MS patients, meaning it is not approved as a therapy for this disease.
MS affects women mostly in their fertile years, but few studies have addressed the safety of taking MS therapies, like rituximab, during breastfeeding.
This lack of information forces “many women to choose between treating their neurologic disease or breastfeeding their infant, despite the many benefits of breastfeeding,” the researchers wrote.
Antibodies are large and not expected to pass to breast milk, but scientific proof is lacking.
A team led by researchers at the University of California, San Francisco (UCSF) measured the levels of rituximab in breast milk from women with MS taking the medicine, who were enrolled in the UCSF pregnancy registry for women with demyelinating diseases.
Researchers collected mature milk samples from nine women (mean age of 34). All were treated with rituximab while breastfeeding or shortly after weaning. All had RRMS (mean disease duration of 4 years) with mild disability, as shown by a maximum score of 2 in the Expanded Disability status scale (EDSS) — a method of quantifying disability in MS, with higher EDSS scores indicating greater disability.
Four of the women analyzed also received rituximab in the six months before becoming pregnant. A fifth was treated with Biogen’s Tecfidera (dimethyl fumarate) prior to her pregnancy, and a sixth with Gilenya (fingolimod, marketed by Novartis) followed by glatiramer acetate (sold as Copaxone by Teva Pharmaceuticals, among other brand names), which she continued on during the pregnancy.
The remaining three women did not use a disease-modifying therapy in the six months before their pregnancy.
Researchers collected serial breast milk samples from four women before an infusion with rituximab, and at specific time points after infusion — 8, 24, and 48 hours; and seven, 18 to 21, and 30 days. The other five patients provided one to two samples at several time points after a rituximab infusion.
The median time between delivery and a single rituximab treatment was six months (range 1.5 to 11 months). Most of those analyzed received a single dose of rituximab infusion (either 500 or 1,000 mg dose), and two patients had two infusions after delivery.
In total, the nine women provided 30 breast milk samples, with four patients providing at least five consecutive breast milk samples that allowed researchers to measure the concentration of rituximab over time.
The median levels of rituximab were low in the breast milk of the four women with serial samples — a median 0.063 ug/mL (range 0.046–0.097). For these women, the highest concentration of rituximab in the milk was detected between day one and seven after an infusion, with a median maximum concentration of 0.074 μg/mL (range 0.061–0.12).
Based on these results, researchers estimated that the median daily dose of rituximab was 0.0094 mg/kg, and the relative infant dose (RID) was 0.08%. An acceptable RID is less than 10%. RID estimates an infant drug exposure via breast milk.
The concentrations of rituximab were similar across those patients providing only one to two samples for analysis.
In one treated with 1,000 mg of rituximab nine months after delivery, the concentration in the milk rose to 0.29 ug/mL 11 days after treatment. Despite this, the RID remained low, at 0.33%.
One woman gave samples at 60 and 90 days after an infusion, and an analysis found her rituximab milk levels “reassuringly very low with a nearly undetectable level by 90 days.”
Infections were found to be few, and not serious, in babies born to four of the five mothers who breastfed after rituximab treatment — all after delivery, with three also also treated in the months before their pregnancy. Data was lacking for one infant born to this group.
One baby who was exposed earliest and at the highest dose to rituximab via breast milk developed the most infections. Still, these were considered mild and common to infancy. They included gastroesophageal reflux disease (GERD), an inflamed esophagus (esophagitis), and upper respiratory tract infections, the study reported.
No delays in development or growth were seen in babies followed up to eight and 12 months after birth.
Overall, the results suggest that a single rituximab infusion at a dose of 500 or 1,000 mg results in very low levels of the medicine in breast milk, indicating minimal transfer to a breastfeeding infant.
“Monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding,” the team concluded, while recommending that further study be done.