Managing Pregnant Patients With Multiple Sclerosis

Andrew N. Wilner, MD; Maria Houtchens, MD


June 30, 2017

Andrew N. Wilner, MD: Welcome to Medscape. I am Dr Andrew Wilner. Today I have the pleasure of speaking with Dr Maria Houtchens. Dr Houtchens is a specialist in multiple sclerosis and is director of women's health at the Partners Multiple Sclerosis Center. Welcome, Dr Houtchens.

Maria Houtchens, MD: Thank you very much. It is my pleasure to be here.

Dr Wilner: I was working at the hospital, unfortunately, during the AAN [American Academy of Neurology 2017 Annual Meeting]. I understand that I missed a couple of very important posters. I wanted to catch up and find out all about them.

Dr Houtchens: I am happy to help out.

Dr Wilner: You had two posters.[1,2] Can you tell me about those?

Dr Houtchens: We have done some work looking at pregnancy-related issues in multiple sclerosis (MS) patients. It is a very important question. We have many patients that we care for. We have young women, or women of childbearing age, who are interested in pregnancy. There are many unanswered questions. The two that we address the most in the two posters, respectively, are on pregnancy complications in women with and without MS, and on what happens with relapse rates in patients. We have a little bit more information about the second than the first issue, but nonetheless there are some interesting things we have found involved with those questions.

Dr Wilner: MS preferentially affects women. It preferentially affects women in the childbearing years. Is it safe for women with MS to have children?

Dr Houtchens: It's safe but there are some specific issues that need to be addressed, depending on a particular woman's situation in terms of how stable the disease is and what medication she is taking. Counseling is also very important [to help patients] know what to expect before pregnancy, during pregnancy, and after pregnancy—and also to address any issues about the baby. Yes, it is very safe and yes, we need to be educated about how to counsel patients.

Dr Wilner: This sounds like more than a 15-minute visit. There are many medications, some of which are quite toxic. I would imagine that pregnancy planning would be very important in this situation.

Dr Houtchens: Yes. Absolutely. We have done some other work that we presented at earlier meetings looking at pregnancy rates in MS patients. We know now that although the general trend in the Unites States, in terms of women getting pregnant, has been a little bit on the downslope in the past decade or so, in fact women with MS are more likely to get pregnant now. The pregnancy trends have been upgoing in our patients, which is wonderful. We credit that to, perhaps, some of the work that we are doing.

Dr Wilner: Yes, maybe better education and less fear. I am an epileptologist and we have looked at this question for a long time for women with epilepsy. Is it safe for them? How does it affect their seizure control? In MS, how does being pregnant affect the disease course?

Dr Houtchens: It is very interesting. We and other people looked at relapse rates in pregnancy. This is something that has been studied [in the past], first by a European group. The study was published and called PRIMS (Pregnancy in Multiple Sclerosis).[3] It's the first prospective study that looked at relapse rates in MS patients. From that study, we know that women with MS are less likely to have an attack throughout the pregnancy. In fact, they do very well. After they deliver, there is a higher likelihood of them having a relapse. This information is known and we use it in counseling of patients.

We look at that and also the utilization of medications before pregnancy, throughout, and after pregnancy. Does that relate in any way to women's relapse rate? In other words, if they have an attack in the year preceding pregnancy, or if they have two attacks or three attacks, are they more likely to be treated, and over what time period? Are they more likely to resume their treatment after they have delivered, and how quickly? All of these questions we did not have good answers to before, and now we at least have some idea.

Dr Wilner: It sounds particularly interesting that the relapse rate decreases while the woman is pregnant, during which time she may even be taking fewer medicines or lower doses. That is what happens in epilepsy; the women are not keen on taking their medicine at that time. Here, you have a situation where the women are actually doing better because of their pregnancy. It raises the question: Is there some hormonal effect of being pregnant that suppresses the relapse rate?

Dr Houtchens: Most likely. There is a shift in pregnancy that is known, from prolonged inflammatory to the anti-inflammatory, if you will, immune state. We know this. Many autoimmune diseases, of which MS is one, tend to improve in pregnancy. Not all, but many certainly do. It is not necessarily surprising to see this effect with MS.

You are right. In term of medications, as opposed to epilepsy, we tend to not use medications on pregnant MS patients. At least, as a general guidance, most of our women, all of our women perhaps, are off treatment for the duration of pregnancy. The question is: How many woman anticipating pregnancy are taking disease-modifying treatments? Are there any who at least get their prescriptions filled? That is really what we looked at in this study.

This is a claims-based project. The benefit is that we have very large numbers of patient records that we can assess. The downside is that we don't know what happened to each individual patient. We do the study looking at prescriptions in this project. We are looking at the drug utilization in pregnancy and after pregnancy.

[First we looked] at all eligible patients who could be treated with disease-modifying therapies. Out of the sample we looked at, about 2100 or so patients, only about 25% were getting prescribed medication. It is a quarter of patients. This was unexpectedly low for me. There are some patients who still had their prescriptions filled throughout pregnancy. Again, I do not know whether they took the medication. At least looking at prescriptions, between 2% and 5% had prescriptions filled throughout pregnancy. Most of them were in the first trimester, possibly reflecting a lag. The prescription was filled before they got pregnant but is still reflected in that record.

Dr Wilner: Is there a drug that is safe in pregnancy for women with MS who want to become pregnant, and which they can continue during pregnancy? Is there such a thing?

Dr Houtchens: In general, our recommendation to our patients is to be off therapy. MS patients have good enough "treatment" from pregnancy itself. Their attack rate really halves during the second and third trimesters. It is a good-enough therapy to be pregnant.

However, injectable medications—in particular, glatiramer acetate—using the old FDA pregnancy categories, had a designation of pregnancy category B. We know that last summer these categories changed and now we do not have letter designation. B is the safest you can get. There are a few drugs that have this designation. Theoretically, or hypothetically, if you have a very active patient with MS, I suppose you can keep them on glatiramer acetate throughout pregnancy. I know that some physicians anecdotally have done that. Again, this is not an official recommendation.

Dr Wilner: It sounds like the best treatment would be to somehow manipulate the hormonal balance so that the body thinks it is pregnant indefinitely. That is relatively immunosuppressed. Then, like with alcoholics, if you don't want an alcohol withdrawal seizure, the best thing to do is not to stop drinking. It is not practical advice.

Dr Houtchens: It is not practical at all.

Dr Wilner: What about the birth control pill? That simulates pregnancy. Does that do anything for relapse rates?

Dr Houtchens: That is a very good question. Birth control pills do not simulate pregnancy. Pregnancy is a unique state. The types of estrogens that are present in the woman's body in pregnancy are not the same types that you use in birth control pills. Plus, there are all kinds of additional hormones that are being produced in a pregnant woman's body, including the placenta, that we cannot re-create in any other state very easily. There is a reason that the woman is pregnant for 9 months at a time, and so many times out of a lifetime. It is wonderful in some ways, but it is not that great in other ways. I think that we will have difficulty maintaining that level of hormonal stimulation in a woman for an extended period because of all kinds of complications that could be associated with high-level estrogens beyond 9 months or beyond 18 months, or what have you.

Having said that, there were some studies looking at the effects of estrogen supplementation on MS outcomes. The studies are a little bit conflicting. The phase 2 study that was done in California, looking at MRI as outcomes, appeared to be positive. That was some years ago. The more recent study[4] that was published, looking at relapse rate outcomes, was a little more conflicting; it was not clear that there was a significant effect.

I would not prescribe high-dose estrogen to my patients without having more data. However, another interesting point from our work that I would like to make is that physicians are certainly starting to think about the risks versus benefits of treatment, and are trying to stratify their patients a little bit in terms of how many relapses they have annually and how many patients should really be taking something even if they are anticipating pregnancy. This is fairly evident.

If you look at our poster, there is a figure that shows the proportion of women with MS who are on therapy based on how many attacks they had in the period that was studied—so, 9-12 months before pregnancy, 6-9 months, and so on and so forth, and postpartum as well. As expected, we see that physicians are using disease-modifying treatments, recommending them, and prescribing them more so for patients who have more frequent relapses. It is self-evident, but it is nice to be able to see that documented on thousands of patient records.

Dr Wilner: What is your next project, Dr Houtchens?

Dr Houtchens: Oh my goodness, we have so many. The one that I want to specifically mention today is a study that we are doing called PREG-MS (New England Multiple Sclerosis Pregnancy Registry). It is a unique study. If you look at what has been published so far in the United States, there is a clear lack of prospective registry-type data that would be placed on a disease state, such as MS, rather than a particular medication as it relates to pregnancies.

We are doing a study in Boston, Massachusetts, that involves most providers who see many MS patients in New England states. We are going to prospectively collect [data on] pregnant women with MS. We are going to look at the outcomes. We are going to look at exposures. We are going to look at outcomes for their babies, hopefully after 3 months of age. This is not too dissimilar to what was done in the epilepsy world some years ago. We hope to be able to provide real-world prospective data that we can use to counsel our patients better down the road. This is the most exciting project that I am currently involved in spearheading.

Dr Wilner: I will have to make sure that I am at AAN next year so that I can see the poster on this and other research that you have been working on. Dr Houtchens, thank you very much for joining us today on Medscape. I learned a lot and it sounds like very worthwhile, interesting, and helpful research for women with MS.

Dr Houtchens: Thank you very much for the invitation. It was a pleasure.


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