NCTalks with Jan Hillert: pregnancy outcomes in multiple sclerosis
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In this podcast, we spoke with Professor Jan Hillert (Karolinska Institute, Sweden) about the challenges faced for people living with multiple sclerosis (MS) related to pregnancy and pregnancy outcomes, and how their recent study could help to overcome these challenges.
Find out more about the recent study in our Publication In Focus here >>>
Transcript:
Please could you introduce yourself and tell our listeners a bit about your research background and current research interests?
Yes, certainly Rachel. I’m a Professor of Neurology, at the Karolinska in Stockholm, and I’m a Senior Consultant in Neurology. I’ve been specializing on seeing MS patients for the past 30 years. I’m also known for having started and chairing the Swedish MS Registry, which collects clinical data on MS patients. It’s used nationwide and we have big numbers. We can do lots of interesting and relevant research using this registry. Therefore, my focus in research these days is within the area of real-world evidence research. This means that we try to answer questions on the natural course of MS. One of the key things to be researched, of course, is how we best use disease-modifying treatments, how we get the best efficacy, how they compare with each other, and at least, what the safety is for these treatments and that also includes pregnancy safety in the context of pregnancies.
How do the clinicians currently treat pregnant patients with multiple sclerosis?
Of course, MS is a disease that affects more women than men and it typically starts in the reproductive age. This means that patients, female patients with MS need to have some way to deal with their MS during pregnancies. Even though pregnancies do reduce the risk of relapse a bit, there is still for many patients an important need of reducing the risk of relapse during pregnancies. Therefore, we need to find ways to do that.
The problem is that once a drug is approved for the treatment of MS, typically no pregnant patients have been in the randomized control trials. We have no idea or there is no data, whether it’s potentially harmful or not. Therefore, we need to reduce the exposure of the disease qualified treatments too in our patients until we know better and since you’re not then of course assumed to become pregnant while on treatment, there will be very sparse data. People even that get pregnant probably will not necessarily report their exposure. Therefore, we need more information and one of the ways to do that is by using registries.
What would you say are the major challenges faced for people living with MS-related to pregnancy and pregnancy outcomes?
Well, the challenge is to balance the need of disease qualification with the safety of the fetus and child and that is a delicate balance that needs to be to be managed somehow and therefore we need the data.
Your recent study focused on pregnancy outcomes after interferon beta exposure among people living with MS. Could you briefly introduce our listeners to the work and summarize the main findings?
Certainly. Before I do that, though, it’s important to realize that even though we’ve had interferon beta for MS for 25 years, we haven’t really known how to deal with it. The reason was that in the beginning, we had the idea from animal studies and from some clinical experience that maybe there was a risk of spontaneous abortions in people on interferon beta.
Interferon beta is a very, what we call pleiotropic substance. It exists in the body, has multiple functions in many physiological systems. We don’t really know what happens if we give you know more of it and therefore it was reasonable to be careful. There have been some studies, but we haven’t really had studies of really good quality and that’s why where this study comes in. This study was then requested by the European Medicines Agency because there wasn’t enough data. The study was based on the national registries or national registries in Sweden and Finland. These were not MS registries, these were medical and administrative registries of various kinds, including disease, events, the prescription of pharma, of course also, and I come back to why that is important.
What we did here was that we looked for the frequency of serious adverse pregnancy outcomes. Serious adverse pregnancy outcomes included the termination of pregnancies due to fetal anomaly, also a major congenital anomaly, live births, or stillbirths. Of course, we were able to control for a number of factors including the age of mothers, number of previous pregnancies, treatments, et cetera. In order to know that what we looked for was actually the effect of interferon-beta exposure. The big benefit of this study was that we could compare pregnancies on interferon beta exposure, exposed to interferon beta to pregnancies without exposure and that is unique to this study.
In total, we looked at over 2,800 pregnancies in over 1,900 women. This included almost 800 pregnancies with interferon beta exposure and 1,600 plus pregnancies without exposure. These were big numbers. The overall outcome was that we didn’t find any sign of an increased prevalence of any adverse pregnancy outcome.
Overall, the rate was 2.2% in the exposed pregnancies, but higher 4% in the unexposed pregnancies. The difference however was not significant, but clearly no difference and if you go to the certain types of adverse outcomes, we didn’t see anything further at all. For the congenital abnormal – abnormalities, we had 1.8% in the live births of the exposed and 3.3% among those not exposed.
For spontaneous abortion, there was no difference. For ectopic pregnancies, elective termination didn’t see anything. The stillbirth risk was also the same, 0.3% in the exposed and 0.6% in the unexposed. We did a number of additional adjusted statistical analyses and they also failed to show any difference. Very clearly, there was no increased risk of any adverse pregnancy outcome, which was really good to see.
How does this study differ from previous studies investigating interferon-beta pregnancy? I know that you mentioned that it’s unique due to the ability to compare the pregnancies. Do you want to expand on that?
I mean, that of course is obvious that you need to compare with something, of course, you can compare to what you know about the risks of adverse events of the general population. But it’s always better to have a comparable group. Of course, we have been collecting or everyone has been collecting information on pregnancies, but unless you do it on interferon beta for many years, but unless you do it in a systematic way where you know that you collect equally well for the exposed and non-exposed pregnancies, only then can you really tell whether there is a difference. So that indeed is a very big benefit.
The other big advantage lies in the same thing, and that is what we refer to as a population-based study. If we include all the cases in two populations as here, then we know that they are representative at least of the situation in those countries, evidently and that is also a big advantage. There are, of course, some limitations to these studies. For instance, spontaneous abortions, only those that require hospitalization will be recorded. The exposure data, I mean, whether people are on drugs or not, is based on pharmacy data and we can’t be certain that people have actually been on rotating the medication only because they’ve been to the pharmacy collecting their drug but it’s an acceptable approximation of course. This is, in many ways, the optimal study to study something which is not supposed to happen, like pregnancy exposed to disease-modifying treatments.
Overall, what would you say this study means for clinicians and people who are pregnant and living with MS? How can interferon-beta help to overcome the challenges that we mentioned in this podcast?
Well, since we know that interferon-beta does reduce relapse rate, does reduce the risk of disability, it’s of course of great benefit to be able to use it when needed. The study was, as I said, before, requested by the EMA, European Medicines Agency. This also led to a change in the label with the EMA on interferon beta in MS. Now you are allowed to use it when needed and that is indeed a big, big advantage.
How do you hope MS treatment for pregnant patients will evolve in the clinic over the next five years?
Very good question. This is a significant step. We need more data on pregnancies for the other disease-modifying treatments. We have an increasing body of evidence showing that the earlier you get on treatment, the longer time on treatment, the more efficacious treatments you have the better for our MS patients in the long term, so to be able to provide an efficient way of controlling the inflammation on multiple sclerosis over the course of the disease the better.
I hope, indeed hope and I expect there to be other studies for the other disease-modifying treatments. Most important that we get data also for the second-line treatments, so that’s what I hope and what I expect to get to coming years and that – there this study I think is a very nice first step in showing how this could be done to get such data which is critically needed.
Do you have any closing comments that you’d like to make?
I would like to thank everyone who listens to this, and I hope that we’ll be back with more information in the future on these studies. This is an important clinical and everyday problem for our patients with multiple sclerosis. Thank you.
Disclaimer
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Neuro Central or Future Science Group.
Meet the speaker:
Prof Dr Jan Hillert (Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden)
Jan Hillert has been Professor of Neurology at the Karolinska Institute since 2001, and in 2010 was appointed Chairman of the Department of Clinical Neuroscience. Professor Hillert has led an MS clinic for over 10 years and is founding chair of the Swedish Multiple Sclerosis Registry, which contains information on 15,000 MS patients. He is actively engaged in several MS clinical trials and has published 240 peer-reviewed papers. Professor Hillert’s research primarily focuses on the genetic aspects of MS and has contributed to the discovery of several MS genes. Additional research interests include immunology and treatment aspects of MS, including treatment-induced antibodies. Current research efforts focus on translational epidemiology, integrating clinical, genetic, environmental, and public registry data both nationally and internationally.
