With multiple sclerosis (MS) disproportionately affecting women of childbearing age, breastfeeding is a high-agenda topic among the research and healthcare professional community. With diagnosis and treatment now occurring earlier on in the disease course, and an ever-expanding number of disease modifying therapies (DMTs) becoming available, the debate is intensifying.
That’s why we have included MS and breastfeeding in our 10 Hot Topic sessions at this year’s 9th Joint ECTRIMS–ACTRIMS Meeting, MSMilan2023. Ahead of the meeting, which will be held in-person and online in October, we look at the emerging evidence base, the questions still in need of investigation, and what our speakers will add to the debate.
The story so far
The literature shows that women are more likely to develop MS than men [1], and that the current average age of diagnosis is between 20 and 40 years [2]. As such, many women will develop the condition before starting or completing their families.
Yet while MS does not affect fertility or the chances of a healthy pregnancy [1], many debate the safety of DMTs during pregnancy and post-partum. While the evidence suggests that pregnancy protects against relapse, allowing DMTs to be stopped in some women with MS during this time, it also points to the risk of disease rebound in others. A rebound in inflammatory disease activity can be seen during pregnancy in those who withdraw from some high efficacy drugs such as natalizumab [3], and, furthermore, is well-described in many cohorts in the post-partum period [4].
A historical lack of evidence to support the safety of DMT use in breastfeeding mothers and their infants means that, for years, women have been forced to choose between breastfeeding and resuming treatment [1].
With breastfeeding proffering “unmatched physical and psychological benefits for infants and mothers” [3], this is a far from ideal dilemma. Recent reviews of the available evidence have argued that this all or nothing approach should be resigned to the history books.
Intra DMT differences
DMTs are generally contraindicated during breastfeeding as they may transfer into breast milk, resulting in infant exposure. A number of factors influence an agent’s ability to transfer into breastmilk, including its molecular weight, half-life, capacity for protein binding, solubility, metabolism, relevant active transport mechanisms, and volume of distribution [3].
As large molecules that bind to T-cells, interferons (IFN) have limited capacity to pass into breastmilk, confirmed by a number of studies in nursing women [3]. As such, INF-b is licensed for use during breastfeeding by the European Medicines Agency (EMA) [1].
Similarly, experts argue that it is extremely unlikely that glatiramer acetate, another large molecule, could transfer into milk, a hypothesis that has been backed up by a number of small studies, enabling a change in the licensing conditions in 2022 to allow breastfeeding on treatment [3].
It is unclear whether the oral DMTs fingolimod and teriflunomide transfer into breastmilk, with both European and US regulators referencing a lack of available evidence [1,3]. There is very limited data surrounding dimethyl fumarate, with small studies showing low levels of transfer of active metabolite. The Summary of Product Characteristics (SMpC), however, recommends caution and an individualised approach [5]. Cladribine has a short plasma life, and given the limited treatment duration the SmPC recommends women suspend breastfeeding whilst taking medication and for seven days after administration [1,3].
Studies have found monoclonal antibodies (mAbs) in breastmilk, but only at levels below the 10% relative infant dose that is generally considered significant. There is, however, a theoretical risk around cumulative dosage in mothers who choose to breastfeed on natalizumab that warrants further investigation.
Further research needed
There is also some suggestion that breastfeeding can protect against disability and relapse [6].
One meta-analysis reported that breastfeeding women were around two times less likely to have a post-partum relapse than their non-breastfeeding counterparts [7]. And a recent systematic review and meta-analysis of 24 publications, including a total of 2,974 women, found that breastfeeding was associated with an odds ratio for post-partum relapses of 0.63, compared to non-breastfeeding women [8].
However, it is still unclear whether these findings resulted from the breastfeeding itself, from post-partum resumption of treatment with DMTs, or from reverse causation, where relapse risk affected clinical decision making around therapy resumption.
MSMilan2023
MSMilan2023 will add to the evidence base and bring delegates right up to date with the latest thinking in this fast moving area of research.
During Scientific Session 20: Female Health on Friday 13 October, Assistant Professor Kristen Krysko, staff neurologist at Unity Health Toronto, St Michael’s Hospital, Canada, will give a talk entitled Lessons learned from RCTs, registries and real-world experiences for breastfeeding.
View the programme and secure your online or in-person place at MSMilan2023 >> here.
[1] Dobson, R., & Hellwig, K. (2021). Use of disease-modifying drugs during pregnancy and breastfeeding. Current opinion in neurology, 34(3), 303-311.
[2] Hansen, M. R., & Okuda, D. T. (2018). Multiple sclerosis in the contemporary age: understanding the millennial patient with multiple sclerosis to create next-generation care. Neurologic Clinics, 36(1), 219-230.
[3] Yeh, W. Z., Widyastuti, P. A., Van der Walt, A., Stankovich, J., Havrdova, E., Horakova, D., … & MSBase Study Group. (2021). Natalizumab, fingolimod, and dimethyl fumarate use and pregnancy-related relapse and disability in women with multiple sclerosis. Neurology, 96(24), e2989-e3002.
[4] Capone, F., Albanese, A., Quadri, G., Di Lazzaro, V., Falato, E., Cortese, A., … & Ferraro, E. (2022). Disease-Modifying Drugs and Breastfeeding in Multiple Sclerosis: A Narrative Literature Review. Frontiers in Neurology, 440.
[5] EMC. Tecfidera 120mg gastro-resistant hard capsules. (2022). Available at: https://www.medicines.org.uk/emc/product/5256/smpc#gref Last accessed: 21 June 2023
[6] Langer-Gould A, Huang SM, Gupta R, Leimpeter AD, Greenwood E, Albers KB, et al.. Exclusive breastfeeding and the risk of postpartum relapses in women with multiple sclerosis. Arch Neurol. (2009) 66:958–63.
[7] Pakpoor J, Disanto G, Lacey MV, Hellwig K, Giovannoni G, Ramagopalan SV. Breastfeeding and multiple sclerosis relapses: a meta-analysis. J Neurol. (2012) 259:2246–8.
[8] Krysko KM, Rutatangwa A, Graves J, Lazar A, Waubant E. Association between breastfeeding and postpartum multiple sclerosis relapses: a systematic review and meta-analysis. JAMA Neurol. (2020) 77:327–38.