During our recent webinar, an expert panel discussed the safety and efficacy of different treatment strategies during pregnancy and breastfeeding in women with multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and neuromyelitis optica spectrum disorders (NMOSD). Dr. Jacqueline Palace, consultant neurologist at the Oxford University Hospitals Trust, facilitated the discussion.
Sandra Vukusic, professor of neurology and head of the MS clinic at the Lyon University Hospital, presented recommendations concerning family planning for women with MS based on existing data.
Since 1998, doctors have been sharing with their patients positive and reassuring messages concerning pregnancy. Indeed, it has been observed that relapses decrease during pregnancy, and slightly increase immediately after delivery. Pregnancy has a neutral global effect on relapses and no impact – neither short- nor long-term – on disability progression. Exclusive breastfeeding can even have protective or neutral effects. However, new questions have arisen over the possibility of continuing disease modifying therapies (DMTs) during the conception period and pregnancy, and thus, new evidence is needed.
Continuing treatment during conception and pregnancy can raise risks for the foetus, such as foetal loss or abnormalities, premature birth, and potential long-term effects. However, there is currently a lack of data on these risks. On the other hand, stopping the treatment may imply risks for the mother – reappearance or even rebound (i.e. increase) of disease activity, accumulation of lesions, and disability. Many issues related to DMTs management are still unsolved. However, Prof. Vukusic warns about the perpetuation of old beliefs. One false belief to be debunked concerns the supposed protective effect of pregnancy that would justify treatment discontinuation. This belief, together with others, should be questioned to minimise underexposure to DMTs during pregnancy, also known as therapeutic inertia.
MS
Prof. Vukusic clarified how biological therapies and small molecules can be transferred to the placenta. While the small molecules passively pass to the placenta and the foetus, biological therapies can be transferred from the maternal blood to the placenta only through an active transporter, which is secreted at the end of the first trimester of pregnancy. The major transfer of biological therapies to the placenta occurs during the third trimester of pregnancy.
In 2022, the French Group for Recommendations in Multiple Sclerosis (France4MS) and the French-speaking society of MS (SFSEP) extensively reviewed the literature [1] and provided guidelines about the management of treatment during pregnancy in women with MS.
Planning
The first question to be addressed is: “How to plan a pregnancy in a woman with MS?”. Pregnancy is not contraindicated in women with MS. It would be important to plan specific consultations with a neurologist to discuss pregnancy planning and adjust accordingly the DMTs and the symptomatic treatments. SFSEP recommends discussing the desire of motherhood whenever a treatment is initiated or switched.
Follow-up
Another relevant issue concerns the follow-up recommended during and after pregnancy. Pregnancy is considered totally normal in women with MS. Therefore, a regular follow-up is recommended, similar to women without MS. The only exception concerns women with an important disability burden, who require multidisciplinary consultations.
Breastfeeding
Not only is breastfeeding not contraindicated, but it is also recommended. Once more, it can be important to anticipate the desire of breastfeeding before delivery to adjust the therapy accordingly.
Prof. Vukusic presented a table with different therapies, indicating the EMA Label, and the recommendation for each therapy in the clinical practice. Some drugs are fully authorised by the European Medicines Agency (EMA), while some others are fully contraindicated during pregnancy and breastfeeding. The table shows that there is no need to delay the start of DMTs in women who plan a pregnancy, given that many DMTs can be used until pregnancy starts. However, it is important to choose the right treatment and to switch to a treatment that implies a low risk for the foetus whenever possible. Moreover, some DMTs can be used during breastfeeding. It is essential to consider that when young women receive a diagnosis of MS, they sometimes assume that this will prevent them from becoming mothers. Therefore, neurologists are encouraged to debunk this false belief as soon as possible, and discuss with their patients the possibility of planning a pregnancy each time a DMT is initiated or switched.
NMOSD and MOGAD
Dr. Tania Kümpfel, associate professor at the Ludwig-Maximilians University (LMU), presented the emerging questions regarding family planning in NMOSD and MOGAD. NMOSD and MOGAD are very rare diseases. Therefore, the amount of data is limited. Recent reviews have suggested discussing pregnancy planning very early and during the diagnosis [2, 3]. Higher rates of miscarriage, preterm births and pre-eclampsia, as well as elected abortions have been shown in women with AQP4-IgG+ NMOSD [4]. Only few recent data are available concerning pregnancy in women with MOGAD, which so far have shown no pregnancy-related complications [5]. A clear increase of relapse rate has been observed during the post-partum period in women with NMOSD, while in women with MOGAD relapse rate decreases during pregnancy and in the post-partum period. Interestingly, some patients received their first diagnosis of MOGAD during pregnancy or in the 12 months after [6]. Higher risks of disease activity during pregnancy have been reported in patients with NMOSD who were active in the years before pregnancy. On the contrary, the risks of relapses during pregnancy are reduced in patients who were stable under treatment for one year before pregnancy.
Dr. Kümpfel presented a table with recommendations concerning the different therapies and, in conclusion, she recommended choosing a safer therapy and with long-lasting biological effects when patients intend to plan a family. The DMT should be restarted or resumed soon after delivery in case of NMOSD. Currently, there is not enough data for MOGAD. A careful benefit/risk assessment should be performed, and an interdisciplinary management is required to monitor the treatment when it is continued during pregnancy.
Watch the webinar on demand here.
References
[1] Vukusic S et al. Mult. Scler. J. 2023; 29(1): 11-36.
[2] Vukusic S et al. Mult. Scler. J. 2023; 29(1): 37-51.
[3] Kümpfel T et al. J. Neurol. 2024; 271(1): 141-176.
[4] Siriratnam P et al. Autoimmun. Rev. 2023; 103465.
[5] Leite MI et al. Mult. Scler. Relat. Disord. 2023; 104760.
[6] Carra-Dallière C Mult. Scler. J. 2023; 29(2) : 270-276.