Tuesday, 20 May 2014

Clinic Speak: Natalizumab and pregnancy

What do you do about pregnancy if you have highly-active MS? #ClinicSpeak #MSBlog #MSResearch

"Pregnancy is one of the big differentiators when it comes to choosing DMTs. Induction therapies win hands down in the sense that once you have had your course of treatment and your disease is under control you can fall pregnant with some confidence that your are not exposing your unborn baby to potentially toxic (teratogenic) compounds and your MS is unlikely to reactivate post-partum due to rebound disease activity. In comparison, maintenance therapies are complicated to work with when you want to fall pregnant. You generally have to stop medication several months before trying to fall pregnant and you have to worry about the possibility of rebound disease activity post-partum and the issue of breast feeding; a large number of the new small molecules will cross-over into breast milk and have potential effects on the unborn child. This study below addresses rebound activity post-partum; the investigators describe 12 and 13 pregnancies in which natalizumab was started in the last trimester of pregnancy; i.e. before delivery. Five out of 13 babies had some haematological complications with anaemia or low platelet counts. The investigators suggest these complications are mild and transient and worth the risk if the mother has highly active MS. What this study does not address is the issue of stopping natalizumab upfront when you want to fall pregnant. I have personal experience of several patients having horrific rebound activity with disabling attacks prior to falling pregnant. I am aware of several colleagues in the US who now advise their patients to fall pregnant before stopping natalizumab and rely on the disease-modifying effect of pregnancy to keep the disease under control before restarting it post-partum. The latter practice is not evidence-based, but does allow woman some control of their disease whilst trying to have a child. The data on natalizumab being teratogenic is simply not good enough at present to be confident that this approach is the right one. I suspect the therapeutic target of natalizumab, VLA4, may play a role in foetal development."


"The following are a list of questions that neurologists need to be able to answer about MS and pregnancy and fertility."
  1. Does MS affect my fertility? 
  2. Will pregnancy affect the course of my MS? 
  3. Will I be able to breast feed after delivery? 
  4. How long before I fall pregnant must I stop my DMT? 
  5. If I fall pregnant on a DMT will this affect the baby? 
  6. Can I breast feed on my DMT? 
  7. Will I be able to be a good parent if I become disabled from my MS? 
  8. If I become disabled or unemployed as a result of MS will I be able to support my children? 
  9. What is the risk of my children getting MS? 
  10. Can I do anything to prevent them from getting MS? 
  11. Am I more likely to need an assisted delivery because I have MS? 
  12. Will I be able to have a normal vaginal delivery? 
  13. Will I be able to have an epidural during labour? 
  14. How you treat hyperemesis gravidarum during pregnancy? 
  15. Should I continue taking my other drugs for my MS symptoms during pregnancy? 
  16. What is the best treatment strategy for my MS? Should I go onto a DMT and get my MS under control before starting a family or should I first start my family? 
  17. What is the best treatment strategy for my MS to maximise my chances of having a family and keeping my MS under control? 
  18. How will having neutralizing anti-interferon beta antibodies affect my baby? 
  19. Can I have IVF? Will the drugs that are used to induce ovulation affect my MS? 
  20. What dose of vitamin D do you advise during pregnancy? 
  21. Are oral contraceptive safer for my MS? Which contraceptive do you recommend? 
Epub: Haghikia et al. Natalizumab Use During the Third Trimester of Pregnancy.JAMA Neurol. 2014. doi: 10.1001/jamaneurol.2014.209.

IMPORTANCE: Natalizumab reduces multiple sclerosis relapses very effectively; however, severe disease activity may return once natalizumab treatment is withdrawn, as recommended during pregnancy. Sometimes restarting natalizumab treatment may be the best option for the mother, but the consequences for the infant are unknown. Except for a few single case reports, to our knowledge, comprehensive data about third-trimester natalizumab exposure are scant.

OBSERVATIONS: In a case series of 12 women with 13 pregnancies and highly active multiple sclerosis who were treated with natalizumab during their third trimester of pregnancy, we assessed the clinical and laboratory effects on the newborns. We observed mild to moderate haematologic alterations in 10 of 13 infants including thrombocytopaenia and anaemia. In a subsample of 5 mother-child pairs, we analyzed natalizumab levels in the umbilical cord blood. Natalizumab was detectable in all 5 newborns.

CONCLUSION AND RELEVANCE: Natalizumab can be a therapeutic option in MSers with highly active multiple sclerosis during pregnancy. We recommend that a paediatrician be available at the time of delivery to evaluate for potential complications of anaemia and thrombocytopaenia in newborns exposed to natalizumab during the third trimester.


CoI: multiple

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