Plegridy Found at Minimal Levels in Breast Milk, Small Study Reports

Plegridy (peginterferon beta-1a), an approved treatment for relapsing multiple sclerosis (MS), is detected at minimal concentrations in the breast milk of patients using the therapy postpartum, a small study showed.

This is in line with label updates on Plegridy and other interferon beta therapies in Europe and the U.S., noting that levels detected in human milk were negligible, and as such the therapies could be taken while breastfeeding.

Given the limited data available to support such recommendations, however, additional evidence into whether Plegridy, a long-lasting interferon-beta therapy, taken while breastfeeding poses a risk to nursing infants would be welcome, its researchers noted.

The study, “Peginterferon beta-1a concentrations in breast milk of lactating multiple sclerosis patients,” was published in the journal Multiple Sclerosis and Related Disorders.

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Several formulations of interferon-beta, a molecule with anti-inflammatory and immunosuppressive effects, are available as disease-modifying therapies (DMTs) for MS. All are thought to reduce the inflammation and abnormal immune attacks in the brain and spinal cord that drive MS-associated neurodegeneration.

However, “data on the transfer of interferon beta formulations and other DMTs into breast milk are limited,” the researchers wrote.

A previous study reported that the estimated relative infant dose (RID) of Biogen’s Avonex (interferon beta-1a), when injected directly into the muscle, was 0.006% — well below the generally acceptable RID value of less than 10%. RID estimates an infant’s exposure to a medication through breast milk relative to the maternal dose.

However, Biogen’s Plegridy delivers a modified form of interferon-beta-1a that is designed to last longer in the body and allow for less frequent dosing, typically once every two weeks.

Since this modification also increases the therapy’s exposure and biological activity, Biogen, along with researchers in the U.S. and Germany, analyzed the levels of Plegridy in the breast milk of five lactating women with MS, given the therapy as their post-partum DMT.

The five women, with a mean age of 35 and median disease duration of six years, were recruited between July 2017 and March 2019 at the Partners MS Center in Boston and the German Multiple Sclerosis and Pregnancy Registry in Bochum, a city in northwestern Germany.

All started Plegridy treatment, administered as under-the-skin injections, only after their infant was completely weaned off breast milk. Breast milk samples were collected from each breast prior to a first injection of Plegridy and over the next 14 days after taking a full-dose of the therapy (125 micrograms).

Plegridy’s recommended dose is 125 micrograms every other week, but patients are initially given a lower dose, which is gradually increased over the course of one month.

The median interval between each woman giving birth and starting with Plegridy was 29.6 weeks, or about seven months.

After a single full-dose of Plegridy, the median maximum concentration detected in breast milk was 50.3 picograms per milliliter (pg/mL), with one woman showing maximum levels of 126.2 pg/mL and the remaining four having peak levels below 72 pg/mL, results showed.

Maximum levels were detected at a median of four days after the full dose, and most samples no longer had detectable levels in breast milk from day eight onward. Plegridy was still detected at day 14 in the breast milk of the woman with the highest maximum concentration.

Plegridy’s concentration in breast milk over the 14 days was a median of 35.95 pg/mL, reflecting an estimated RID of 0.0054% — nearly 2,000 times lower than the accepted concern level of 10%.

Even when the highest concentration (126.2 pg/mL) was used to make the calculations, the estimated RID was about 0.019%, still well below the accepted 10% exposure threshold.

“Over the course of 2 weeks following a single full dose subcutaneous [under the skin] peginterferon beta-1a injection, minimal concentrations of the drug were detected in the breast milk samples of the cohort of 5 lactating women with MS,” the researchers wrote.

The concentrations of Plegridy found in these breast milk samples could help postpartum patients and their doctors with treatment decisions, the team added.

“There is evidence to suggest, that while women during pregnancy have a decreased risk for MS relapse, there is a transient higher risk of relapse during the postpartum period,” and during this period “treatment decisions that incorporate the net maternal and infant clinical benefit may be necessary.”

However, the researchers wrote, “the interpretation of our study is limited by the small sample size” and by treatment initiation being delayed until the women had finished breastfeeding their infants.

As such, further studies on the use of Plegridy “among pregnant and lactating women with MS are warranted to better define the risk versus benefit ratio and guide treatment with this DMT during pregnancy and lactation,” the researchers added.