Women are typically diagnosed with MS between 20-40 years of age, a time when many may consider falling pregnant and starting a family. Whilst there are many effective therapies currently available to treat MS, there is little evidence around the use of these therapies in pregnancy. Two new studies funded by MS Research Australia are helping to fill this knowledge gap.
There has been limited information available on the safety and effectiveness of MS therapies during pregnancy as clinical trials of MS drug therapies specifically exclude pregnant women. However, we do know from studies in women with MS who are not on any treatment or have taken some of the older MS treatments, that they usually experience lower rates of MS relapse during pregnancy, but have a slightly increased risk of relapse after the birth. You can read more about this here.
We also know very little about what happens with relapses in pregnancy for women treated with the newer MS therapies. Often there are a significant number of discussions that take place with an MS specialist health-care team about MS therapy use in the setting of family planning and before a pregnancy.
But what happens if the therapies are stopped for the pregnancy? Does the pregnancy itself still protect from MS relapses? Alternatively, what happens if a woman continues a modern MS therapy into or throughout the pregnancy?
A new study led by Dr Wei Yeh and Dr Vilija Jokubaitis from Monash University looked to answer these questions. The team examined relapses in women who had been treated with a range of modern MS therapies including natalizumab (Tysabri), fingolimod (Gilenya) and dimethyl fumarate (Tecfidera). This was a large study including 1,998 pregnancies in 1,619 women with MS, using data from the international MS registry, MSBase.
The key findings demonstrated that women who stopped natalizumab or fingolimod for the pregnancy had a higher risk of MS relapse, both during and after the pregnancy. This most likely reflects that these highly effective therapies are usually used in people with active MS and we know that stopping these therapies can lead to disease return or rebound (a worsening of MS after a period of remission). This disease rebound can also occur in people with MS who are not pregnant. We know that pregnancy has a tendency to protect women from MS relapses, but it seems that in this group of women who have been on natalizumab or fingolimod, these protective effects of pregnancy are not enough to prevent relapses.
The general advice is that fingolimod (Gilenya) should be stopped prior to pregnancy, as there is the potential for the foetus to be adversely affected by the drug. Natalizumab (Tysabri) has not been associated with problems to the same degree, although there are still considerations that must be discussed with the treating neurologist. For more information on Australian pregnancy categories for MS medications see here.
In this study, women who continued natalizumab during the pregnancy (up to 34 weeks) had a lower risk of relapse during pregnancy. Restarting natalizumab soon after birth protected against relapses after birth. This means for the women participating in the study who were at a high risk of relapse, natalizumab treatment during and after pregnancy effectively reduced their MS relapses.
A small number of women included in the study were taking dimethyl fumarate (Tecfidera) before or at conception (with the majority stopping therapy at conception). This group had a lower risk of relapse during pregnancy – this may be related to the immune-dampening effects that are known to persist for several months after stopping this therapy, but larger studies are required to confirm this. Reassuringly, the researchers found that worsening of disability during pregnancy was uncommon (less than 6% of the pregnancies from 2011 onwards). The results of this study were published in April 2021 in the prestigious journal, Neurology. A summary of this study from Monash University can also be found here.
Autologous haematopoietic stem cell transplant (AHSCT) is increasingly being used around the world as a treatment for aggressive MS. It is known that AHSCT can cause sterility and premature menopause in people with MS of childbearing age. For those people potentially wanting to conceive after AHSCT, harvesting and storing eggs or sperm before the treatment is often recommended to increase future options for conception.
In Australia, three clinical trials of AHSCT for MS are in progress, including one trial funded by MS Research Australia and the MS Angels, at St Vincent’s Hospital in Sydney. Neurologist Dr Jennifer Massey and her team have published their latest findings on pregnancy after AHSCT for MS. Among 30 women of childbearing age, four pregnancies occurred after AHSCT. Two elective terminations were performed, and the other two pregnancies were carried to term. There were no complications reported for the mother or the newborn in either case. Of the 21 men in the trial, one participant has fathered three children since his AHSCT, with no newborn complications.
These results are in line with a 2015 international study of AHSCT for autoimmune disease, which showed that 68% of pregnancies after AHSCT resulted in live, healthy births. The rate of fertility after AHSCT in the new Australian trial was lower than for the general population in Australia, supporting the advice to consider egg/sperm banking for those potentially wanting to conceive after this treatment. This study, published in Multiple Sclerosis Journal is the first to report on fertility outcomes in both sexes after AHSCT for MS. You can read more about AHSCT for MS here.
This work highlights that natalizumab (Tysabri) may be a treatment option for neurologists to consider to protect women who are at high risk of an MS relapse during pregnancy. This research also supports that disability worsening is uncommon in women with MS who are pregnant. Although AHSCT is known to impact fertility, there have been healthy births reported after AHSCT for MS in both men and women. It is essential that people with MS work closely with their MS specialist health-care team to determine the best management for planning their family and for the best treatment options during pregnancy and the post-partum period.