Xavier Montalban, MD, PhD, MBA, Vall d’Hebron University Hospital, Barcelona, Spain, discusses the current treatments for primary and secondary progressive multiple sclerosis (MS). Ocrelizumab is the only approved drug for primary progressive MS (PPMS) and was found in the ORATORIO trial (NCT01194570) to be associated with a 24% reduction in disability progression; however, addressing patient comorbidities and lifestyle and environmental factors such as smoking is equally important. Ocrelizumab is also used to treat secondary progressive MS (SPMS), where oral cladribine, interferon beta-1a, and interferon beta-1b are also recommended. There were few clinical trials available regarding SPMS. The European multicenter trial on interferon beta-1b concluded that the treatment was effective in patients with SPMS, but later, the American study was negative. One other trial on SMPS derived more positive results for siponimod. Overall, further studies need to be conducted to identify more effective treatments for PPMS and SPMS. This interview took place during the XXV World Congress of Neurology (WCN).
Transcript (edited for clarity)
Everybody knows that there are basically two types of progressive MS. The primary and secondary progressive MS. The primary account for 10 to 15% of patients with MS. And secondary means that a number of patients with relapsed and remitting will eventually develop a secondary progressive phase. So the number of patients with progressive MS is in fact huge, and we can estimate about 1.2 million, something like that...
Everybody knows that there are basically two types of progressive MS. The primary and secondary progressive MS. The primary account for 10 to 15% of patients with MS. And secondary means that a number of patients with relapsed and remitting will eventually develop a secondary progressive phase. So the number of patients with progressive MS is in fact huge, and we can estimate about 1.2 million, something like that. What we have now for primary progressive MS is just very easy. It’s just one specific drug, one single drug, which is ocrelizumab. But let me just start by saying that it’s not only treatment of progressive MS, it’s not only about medications. It’s not only about drugs, but it’s also about dealing with a number of environmental factors and comorbidities. So we have to recommend our patients to take vitamin D just to give you one example, not to smoke.
For instance, this is really very important. Avoid, of course, concussions, obesity is not a good factor either. And then a number of comorbidities such as hypertension, diabetes, obesity, as I said before. This preventive measures are equally important to the medication itself. So I would like to highlight that. And I, during my participation in the World Congress, I insisted on this specific point. And then as I said, for primary progressive MS. We just have one single medication approved in the FDA and by the EMA and in other countries as well, which is ocrelizumab. There is only one single trial that we called ORATORIO, and ocrelizumab showed 24% reduction in the confirmed disability progression, which was a statistically significant other endpoint went in the same direction as well. So hopefully in the next future, in the future, we’ll have other medications to treat PPMS as we call it.
Then for SPMS in fact, if we look to the label of a number of medications, we have a bunch of treatments to treat SPMS, just to give you a number of a number of examples, ocrelizumab for sure, oral cladribine, ponesimod, ozanimod, ofatumumab. And in fact, even interferon-1b and 1a. All of them they have in the label to treat patients with relapsing MS. Which includes secondary, progressive MS as well. Mainly in US and less in Europe. However, we have to be very honest. There are only two trials, very much dedicated to SPMS. One was many years ago, the European SPMS trial with interferon beta-1b that was positive, but later on the American trial was negative. So we are not using in fact interferon beta to treat our patients with SPMS.
And then siponimod, which is the real one in the sense that the trial is just on patients with SPMS was positive. The efficacy was moderate, but statistically significant. And again, all the secondary endpoints went in the right direction. I have to say as well, that siponimod and, and also ocrelizumab for PPMS, they work much better when there are prior relapses. When the disease is rapidly evolving, when we have an active baseline MRI. And of course, as always in young people with a shorter disease duration treatment, naive and lowers EDSS scores. I think this is a summary of what we have nowadays to treat patients with progressive MS.
Dr Montalban has received speaking honoraria and/or travel expenses for participation in scientific meetings, and/or has been a steering committee member of clinical trials and/or participated in advisory boards of clinical trials in the past years with Actelion, Alexion, Bayer, Biogen, Bristol-Myers Squibb/Celgene, EMD Serono, Genzyme, Hoffmann-La Roche, Immunic, Janssen Pharmaceuticals, Medday, Merck, Mylan, Nervgen, Novartis, Sanofi-Genzyme, Teva Pharmaceutical, TG Therapeutics, Excemed, MSIF and NMSS.