Booming the babies: ‘DMT-free’ family action!

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The mean age of women in the European Union on giving birth to their first child has gradually increased from 28.8 years in 2013 to 29.3 years in 2018. Importantly, it has increased in all EU countries over this period. As the majority of female pwMS develop the disease in their early thirties, it’s therefore not acceptable to take decisions on DMTs without discussing the implications for family planning. Especially, as pwMS in their thirties will not be keen on postponing pregnancy for one or two years to organise a DMT switch towards a more MS and/or pregnancy safe option. 

Family planning implies a triad: conception, pregnancy and breastfeeding. In practice, DMTs need to be safe on all three domains to earn their spot on a future mother’s lap. However, there are four important issues when reconciling the triad with DMT strategies: 

  1. Only two of the DMTs in the extensive MS armamentarium, Copaxone and interferons, are entirely safe during the full triad.
  2. Copaxone and interferons have a low efficacy when it comes to preventing MS-related brain inflammation 
  3. When DMTs are stopped, they often require three to four months to reach their full anti-inflammatory potency after being restarted, or they are associated with rebound MS disease activity
  4. Relapses during pregnancy or in the postpartum period are associated with an increased risk of sustained and long-term disability 
A staff nurse greets some new arrivals at the Queen Charlotte Hospital in London, 1945. Source: https://rarehistoricalphotos.com/boomer-generation-1945-1955/

Although there is considerable evidence that DMTs such as Tecfidera are likely to be safe during the triad, many female pwMS will prefer stopping the DMT when there is remaining doubt about safety or teratogenicity. Pausing treatment will leave these pwMS unprotected for about two years on average – assuming ‘Mao-istically’ the family planning only entails one child. 

Therefore, I would argue it is paramount that with every female pwMS who is prior to completing her family and prior to starting a DMT, a ‘DMT-free’ option is discussed. As words are always – and especially in MS – arbitrary labels, this should be done irrespective of whether the disease course is considered ‘mild’ or ‘aggressive’. ‘DMT-free’ options are only possible when treatment results in prolonged disease control (i.e. several years) after a short treatment interval. This is the concept of induction therapies such as cladribine, alemtuzumab (and potentially also anti-CD20) which have a biological effect that outlasts exposure to the drug many times. After completing the two treatment cycles in year one and two, disease activity is monitored clinically and radiologically conveying into the perfect window for family planning and – more satisfactory – action. 

Twitter: @SmetsIde

Disclaimer: Please note that the opinions expressed here are those of dr. Ide Smets and do not necessarily reflect the position of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust.

Review Curr Opin Neurol 2021 Jun 1;34(3):303-311.doi: 10.1097/WCO.0000000000000922.

Use of disease-modifying drugs during pregnancy and breastfeeding

Ruth Dobson, Kerstin Hellwig

  • PMID: 33709977
  • DOI: 10.1097/WCO.0000000000000922

Abstract

Purpose of review: The fact that multiple sclerosis (MS) predominantly affects women has been recognized for many years. As the age at diagnosis is decreasing, and treatment options are becoming more complex, increasing numbers of women are facing decisions about the use of disease modifying therapy (DMT) in and around pregnancy. Recent findings: New data are rapidly becoming available, particularly regarding the safety of therapies in both pregnancy and breastfeeding. Effective treatment and suppression of relapses is key to ensuring good outcomes in the longer term for the woman, however this must be balanced against individual risk of relapse and risks to the fetus. Women should be advised that it is possible to breastfeed while taking selected DMT. Summary: In this review, we discuss evidence surrounding the safety of DMTs in both pregnancy and breastfeeding, and use this knowledge to suggest approaches to pregnancy and family planning in women with MS.

About the author

Ide Smets

18 comments

  • I should not comment on this not being a woman so not directly involved… would it make sense to consider formula milk feeding to reduce the DMT free time? It would be a way to derisk the post pregnancy shortening time to DMT restart. It is not the best for the baby but it could be a compromise for mothers safety.

    • That is an option, and is often done for pwMS on Tysabri before falling pregnant as there is a high risk of rebound disease activity for the mother. However, most other DMTs only work after three months, and thus have no effect in preventing post-partum relapses when initiated short after giving birth.

    • My wife really wanted to breastfeed and she was advised by her neurologist she could do it for 6 months before starting again on Ocrevus. We were told there are studies saying that breastfeeding is reducing the disease activity during the first 6 months. After this period the the effect fades so at that point she needed to start her DMT again. Giving up breastfeeding and switching to formula milk was not easy, but those 6 months were invaluable for her.

      • There is indeed limited evidence that breastfeeding would reduce the risk of postpartum relapses, but it has been difficult to objectify because of different confounders such as early resumption of DMTs and prepregnancy relapse rate. Nonetheless, you justly highlight that female pwMS want the full mother package including breastfeeding, even though it might be harmful for them to postpone DMT resumption. And that is exactly why induction or immune reconstitution therapies should be given priority when choosing DMT.

      • I fully understand this point… it is just an option to consider, it was not intended as advice or recommendation

  • Hi and tx for posting!
    As covid data shows that ocrevus interruption is „safe“ until 15-18m a pregnancy after 6m from last infusion should be „optimal“ timing? thank you for your opinion on that!

    • This is probably true if you have had four OCR cycles before, but at the moment it’s still an assumption and solid data are lacking. Therefore, many neurologists will propose a new cycle 6-8 months after the previous cycle, which will leave pwMS with a 4 month gap to fall pregnant. Quite stressful. And even if you apply the 18 month gap, the problem remains that if you start trying to conceive 4-6 months after the last infusion, there are about 12 months left to complete the ‘triad’. Biology is not always planable; and and many females, irrespective of MS, have issues ‘timing’ a pregnancy.

      • .. and this is why as someone who was ambivalent about having a child already. I’m even more off-put since being diagnosed with MS. This topic has a big mental impact on me at 32.. I would really appreciate more posts on this topic!

        • I can imagine, for every non-induction DMT there are a lot of insecurities when it comes to safety and ideal timing of stopping/starting, leaving future mothers essentially in limbo about what is best for them and their baby.

          • It’s something I’ve been thinking a lot lately coming up to 2 years on Ocrevus, but I have come to the conclusion I am not ready, mentally for that decision. And the MS has been a big factor.. more than I thought it was. I can see why a lot of women choose not to have children once they have this diagnosis. I would also like to know how common that is…

          • Also, I mean, one to ask at my next appointment… if you are ‘responding’ to Ocrevus. Is this sort of thing ever a reason to be moved to an induction therapy like lemtrada, to make your potential future decisions less stressful? I’m sure it doesn’t work like that.. though.. .

    • Are you referring to the flue vaccine that is required in pregnant women? Anyway, as long as there is B cell depletion the serological conversion after vaccination will be reduced. You can expect B cells to start rising again 6-9 months after the previous infusion, and as soon as there is repopulation with naive B cells you will be able to generate some antibody response. But it is true that if you fall pregnant before, you are likely to have a lower protection from the vaccines.

  • I was diagnosed just as we planned to start a family and I was already mid 30s. My neurologist suggested I placed children on hold, despite my age and desire, so I could have both rounds of lemtrada. He said within 16 months I could return to life as normal knowing I had given myself the best chance. I remember I was so torn when making the decision but I chose lemtrada fortunately so had it as a first line (when it was allowed) don’t and 5 months after round 2 I was pregnant. I was able to breastfeed and was told this would reduce postpartum relapse risk as well. I’m currently NEDA and a mother. The only thing I didn’t fully appreciate was how much monitoring and intervention a wayward post lemtrada thyroid would need in pregnancy. This caused a lot of stress and I believe my case was presented at the BTA annual meeting as the endocrinologists struggled to stabilise it.

    • Thanks for sharing, and this was a very good advice of your neurologist. The blood monitoring with alemtuzumab is definitely a hassle.

  • I think having this conversation is very important as family planning can take a long time from birth control cessation onward, and ideally one would be diagnosed and treated long beforehand. We chose to move forward with fertility treatments on the heels of MS diagnosis, which ended up with good timing once the fertility cycles were dialed in. Our first pregnancy was 4mo after starting Copaxone and the second 8mo after the initial Ocrveus infusions (I relapsed 10mo postpartum on uninterrupted Copaxone treatment). I failed breastfeeding, so that point became moot. Restarting my medication, post section with a newborn and a toddler, was made easier with at home infusions.

    • Exactly, pregnancy, breastfeeding and motherhood complicate life, and make it even more difficult to comply with complicated DMT advices

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