Safety of breast feeding during rituximab treatment in multiple sclerosis

Abstract

Background: There are limited data on the safety of breast feeding during rituximab therapy. Our objective is to determine exposure from breast feeding and biological effects of rituximab in breastfed infants.

Methods: In our case series of six mother-infant pairs, the nursing mothers with relapsing-remitting multiple sclerosis received rituximab during breast feeding. As part of clinical follow-up, six serial breast milk samples, and blood samples from both mothers and infants, were collected and analysed.

Results: The median average rituximab concentration (C_avg) in breast milk was 0.04 µg/mL and the estimated relative infant dose (RID) was 0.07%. The highest measured concentration of rituximab in the breast milk samples was 0.25 µg/mL, giving an estimated RID of 0.26%.All infant serum rituximab concentrations were below 0.01 µg/mL. The CD19 +B cell count values were within the 10th- 90th percentiles of reported normal ranges in healthy infants.

Conclusions: We found minimal transfer of rituximab into breast milk and could not reliably detect levels of rituximab in infant serum. B cell counts in infants were unaffected.

Keywords: multiple sclerosis.

Figure 1

Rituximab concentrations and CD19+ positive cells. (A) In the breast milk samples. Each line represents individual rituximab concentrations (μg/mL) of the patients’ breast milk samples from the day of rituximab infusion (baseline, x=0) and up to five half-lives of rituximab (about 110 days). (B) In the mothers’ serum samples. Each line represents individual serum concentrations of rituximab of the patients from the day of rituximab infusion (baseline, x=0) and up to five half-lives of rituximab (about 110 days). Patient number 3 received a dose of 1000 mg rituximab intravenous, while the other patients received a dose of 500 mg. (C) CD19+ cells in the infants’ blood. Each line represents individual levels of CD19+ cells in the infants’ blood. Infant number 1 is the child of patient number 1, and so on. The first point on every line represents the test taken the same day their mothers received rituximab infusion, x days after birth. 10th–90th percentiles among healthy infants: 300–2000 CD19+ cells/μL aged 0–3 months, 430–3000 CD19+ cells/µL aged 3–6 months.