Dr Riley Bove Discusses Understanding Sex Differences in MS Treatment Responses

It is well known that women are disproportionately affected by multiple sclerosis (MS), but there remains a lack of understanding regarding gender differences in response to treatments for MS, said Riley Bove, MD, assistant professor of neurology at the UCSF Weill Institute for Neurosciences.

Transcript
There are gender differences in MS prevalence with women disproportionately affected by the disease: are there also gender differences in how woman and men respond to treatment?

We don't know. And it's an important question. We think there may be. Men and women in general, sort of absorb metabolize medications differently. Their immune systems are also slightly different, and so they may respond to certain immune modulation differently.

That said, if we actually look at the data from the interventional clinical trials, we really just don't know enough right now. It's a question we think is worth pursuing. And one of the focuses of the talk is really a review that we did have sort of the critical literature in the MS field about disease-modifying therapies. And we just found that not enough was known about men and women at baseline when they enrolled in the trials, and not enough was known about how they responded to the medication, both in terms of therapeutic effects and also side effects.

So, hopefully, the newer studies will shine a more focused light on this question.

What do you attribute the lack of understanding to?

I'm not sure why to date, the literature has not really homed in on the issue. I think there's a couple of possible explanations and there, you know, the answer may lie in several of these. So, for instance, we know that there's a negative publication bias in the literature, in general. And so let's say there are no sex differences, then that may not be published.

There's also a clear scientific bias. A lot of these questions just have not been raised. And it's not that they're not worthy. It's just that they have not been raised. And I'll get back to that. Another hypothesis is that there are differences, but, you know, for marketing purposes, it may not be as attractive to say that either men or women don't respond as well to therapy. And so that, I think, we should think about. And there just may be no differences, right? So, I think we need to just be diligent and do the work and then be able to say with certainty.

And so a fourth reason why we may not have enough knowledge about potential sex differences in either treatment efficacy or side effects is lack of statistical power. And so different studies have to enroll different amounts of men and women to either be representative of the population living with MS—so, 3 to 1 female to male—or perhaps powered enough to look at an effect on MS progression. So you may get closer to 1 to 1 female to male and the progressive MS trials.

But what that means is, if you have a lower percentage, say of men in a trial, the study may not be adequately powered statistically, to find a statistical difference or statistical impact. And so attention also has to be placed on whether the studies are powered statistically to find the differences that you expect.

If we think a little bit about the scientific biases, we know that the more diverse and inclusive the set of scientists and clinicians thinking about these questions is, then the more diverse and inclusive the sciences. And there is the International Women in Multiple Sclerosis consortium that's kind of developed that sort of advocates for the inclusion of women scientists in the steering committees of the clinical trials and so forth, to ensure that diversity of opinion and scientific focus.

In MS, we may not know much about the efficacy of treatments by gender, but do we have some information about adverse events? Is there data on safety of therapies and the differences there may be by gender?

So, we know sex-specific adverse events. So, if you think for instance of you know, breast cancer rates or other sort of things that can only happen in women or men, then those do tend to be reported. But whether other adverse events—infections or infusion reactions or hair loss or other, you know other either side effects or adverse events—happens more in men and women, we don't know.