Experts in neurology comment on factors relating to treatment selection in pregnancy for women with multiple sclerosis; highlighting efficacy and reversibility considerations of disease-modifying therapies.
Jeffrey Dunn, MD: There was an Innsbruck study that I was just looking at that said that if, in 1 cohort of women, an annualized relapse rate was about 0.36% going into pregnancy, and in those first 3 months after giving birth it rose a bit to 0.5%. Although as you know the relapse rate during pregnancy can decrease below baseline. Let’s pivot a moment. We’ve been blessed in this field. The men and women who live with multiple sclerosis have benefited from this explosion of new disease-modifying immunotherapies. In simplistic terms we can say multiple sclerosis is an autoimmune disease where we can treat it effectively and decrease relapse rate, if we use immunotherapies, which sometimes can be associated with suppressing the immune system. While that may be helpful for the mother with multiple sclerosis, that potentially offers some unknown harm, uncalculated harm, to the child. There’s a large spectrum of disease-modifying therapies that have been categorized according to lower efficacy, medium efficacy, higher efficacy. They have different risk-benefit profiles. As you think about this difficult question about treating a woman, either considering pregnancy or who is already pregnant, with disease-modifying therapy, do you have a certain algorithm or approach that you employ that you can share with our colleagues nationally?
Regina Berkovich, MD, PhD: I have to rely on my other expertise in pharmacology. The way I look at it may not be necessarily the most popular view. I approach the women of childbearing age who are likely to get pregnant, and especially those who are looking to get pregnant, my preference would be immunomodulatory drug.
Jeffrey Dunn, MD: To be clear, this would be during pregnancy or prior to, or afterward?
Regina Berkovich, MD, PhD: Prior to pregnancy. As you said, we don’t have that experience of 10, 15 years of monitoring and registry with the immunosuppressive drugs to know what might be the long-term outcome. And therefore, my sense, an instinct of pharmacologist, tells me to focus more on the reversible medications. those are immunomodulatory medications predominantly. Yes, we will have this cohort of women who need the higher efficacy therapy, but even with them, the medications of higher efficacy, we still can subdivide them, differentiate, and find medications which are more modulatory and then some which are more suppressive. Even among those suppressive medications, you can differentiate suppressive reversible or suppressive not so easily reversible.
Jeffrey Dunn, MD: Between those first two categories, would you generally favor an immunomodulatory treatment over an immunosuppressive treatment?
Regina Berkovich, MD, PhD: In general, yes.
Jeffrey Dunn, MD: Yes? And then if you thought that you needed an immunosuppressive therapy, perhaps in a patient who’d shown significant disease activity going into pregnancy, which of the two, would you favor the reversible type of that?
Regina Berkovich, MD, PhD: As a pharmacologist again, we need to clarify terminology. The biggest problems come when people are not clear about what they’re talking about. I’ve noticed that there are some geographical differences in what we classify as a high-efficacy therapy. For example, the clearly immunomodulatory class of sphingosine-1-phosphate receptor [S1P] modulators, they are immunomodulatory, but are they moderate efficacy, or are they higher efficacy? We have a lot of evidence indicating that likely it’s higher efficacy. Perhaps not the highest, but we don’t know, we can’t compare, because no comparison studies were done. Pharmacologically, ideal study would be to bring on the market medication of such class, and compare to another higher efficacy drug. That’s not being done, because then it would require thousands of patients to show the difference. The studies are done the way they are done, which is practical, and that helps us to get medications sooner, which is extremely important as well. When it comes to the decision on which one to go to, I would review all the medications that previously this person was on. I would look at the level of reversibility of the medication. for example, in my view, S1P modulators are immunomodulatory drugs and they are in the class of higher efficacy. But, let’s say this is not an option, and we can look into others. By the level of reversibility, I would always introduce natalizumab, because it’s immunomodulatory, it’s not associated with lymphopenia, we have some good reports coming from Germany about long-term safety, even in those women who continue—in pregnancy. This is all important. And then, here we have 2 classes of different mechanisms of barrier methods, not to introduce barrier method to the question of pregnancy but nevertheless.
Jeffrey Dunn, MD: In an immunologic sense.
Regina Berkovich, MD, PhD: Mechanistically, right. From the mechanism of action. Is there sequestration within the lymphoid tissues or blocking the adhesion molecule in penetration through the blood-brain barrier? I would say that those would be my preferred classes if I have to go with the high-efficacy medication. If we go to the immunosuppressive drugs, if we have to choose within the immunosuppressive drugs, then I would look to the ones with more, higher potential of reversibility.
Transcript Edited for Clarity