The director of the Partners Pediatric Multiple Sclerosis Center at Massachusetts General Hospital spoke about the current landscape of MS treatment.
Tanuja Chitnis, MD
With a robust pipeline and multiple options, the landscape for multiple sclerosis (MS) therapies is far-reaching, but as with many neurological conditions, challenges that need addressing still linger.
To better understand what is currently being developed and the recent improvements that have come about, NeurologyLive spoke with Tanuja Chitnis, MD, the director of the Partners Pediatric Multiple Sclerosis Center at Massachusetts General Hospital. Chitnis detailed the pipeline products that interest her, the recent approval of ocrelizumab for primary progressive MS, and the issues that remain despite the last decade of successes.
Tanuja Chitnis, MD: There’s been a lot of advancement in terms of the [disease-modifying therapies] in the past 10 to 15 years—now we have over 15 DMTs approved for MS, with probably 7 or 8 major classes. We had originally the subcutaneous injections the interferons, those were modestly efficacious, but of course we used them for many years and that was really the first foray into treatment.
Then, of course, we entered the oral era. We got fingolimod (Gilyena) then dimethyl fumarate (Tecfidera), then teriflumonide (Aubagio)—so 3 orals. Sort of dispersed in between we got the first intravenous monoclonal antibodies. The natalizumab (Tysabri) antibody was introduced and then taken off the market, then reintroduced. That was also an important treatment for severe forms of MS, and most recently we have alemtuzumab (Lemtrada), and then of course ocrelizumab (Ocrevus), which many have used as a precursor for rituximab. Within that, it’s wonderful for our patients to have choice, and also for their physicians to have the ability to choose between treatments and to change treatments to another class or another form if there are efficacy issues.
I think the choice that’s available is very helpful and important, and I think now physicians are entering an era, at least I am, where they’re trying to very carefully consider what would be the right match of treatment for their specific patients. That might be based on [adverse] effect profiles and patient’s preference issues. Let’s say [we’re using] an injectable, but they are not amenable to injections and prefer pills—that’s a major factor. Then, starting to think about the type of patient and the severity of their disease and how to match that with any given treatment.
I think within that sort of question we have seen that there are milder DMTs with a more modest effect, and those have a more efficacious profile. So, ranging from about 33% annual reduction relapse rate to about 55% reduction in AAR compared to either placebo or active comparator. We’re kind of getting a sense in that, and another matching point that I think about is maybe a patient who is having more frequent relapses would need a more potent DMT and then matching based on other factors—maybe [adverse]-effect profile, patient preference within a few choices of the more efficacious DMTs.
That starts to summarize my current thoughts on where we are in the DMT space in MS, and there are several in clinical trials, several which are somewhat biosimilars or at least similar mechanisms reactions. So, there are several that are coming down the pike there, and also have a focus on progressive MS. That’s very interesting and that is really an area of need where we do need an effective DMT—of course, we just got the first DMT approved for primary progressive MS with ocrelizumab. More choices in that space would be very helpful.
TC: Certainly now, we need to focus more on the CNS mechanism. These could be inflammatory mechanisms or neurodegenerative mechanisms in progressive MS, and so there are treatments which are focused on astrocytes in the CNS and there is one, siponimod, which of course is a sphingosine 1-phosphate modulator that seems to have sensitivity towards CNS and possibly CNS mechanisms, which seems to have some effect in progressive forms of MS. Along those lines, new treatments which target within CNS mechanisms—whether they’re neuro-inflammatory, astrocytes/microglia, the neurodegenerative component itself, or remyelination. Those are important targets for progressive MS.
TC: What we really have learned is that early treatment seems to be the most efficacious, and there are several studies which have shown the earlier you treat either MS or CIS, that has long-term impacts. Now pediatric MS—of course, one of the studies I’ve been involved in is with the fingolimod study in children with MS, and that had a very positive outcome. It was numerically higher than in adults, part of the function there is there are more relapses in kids, but it does seem to be targeting the early mechanisms of the disease very well. We’re learning, and probably re-learning, that younger patients have a higher relapse rate and that would be the group to use a more efficacious treatment on, of course balancing safety, and ultimately this may lead to significantly improved outcomes for the long-term. I think we’ll have to see, but clearly waiting to treat someone into their 40s and 50s and not treating early on could have detriments.
We also have seen that the clinical trials, in a large meta-analysis, a published meta-analysis looked at the relationship of age and clinical trial to outcomes. Overall, the younger you were, there was a better response to all of the disease modifying treatments, and I think it speaks to the fact that early on early disease, younger disease fits a more inflammatory profile. That’s where these agents that act on the prereferral immune system are the most effective. Then later on, you start to get in the progressive phase and CNS phase and that’s harder to treat.
Transcript edited for clarity.