A comparison of various factors considered when treating primary progressive multiple sclerosis versus secondary progressive multiple sclerosis.
Bruce Cree, MD: We’re going to move on to talk more about PPMS [primary progressive multiple sclerosis] and SPMS [secondary progressive multiple sclerosis] and their treatments. Joe, I’m going to send this topic over to you. Would you compare the treatment for PPMS and SPMS?
Joseph R. Berger, MD: Sure. Why don’t we talk a little about the treatment of progressive disease in general? Up until the ORATORIO study, we didn’t have a treatment for progressive disease, be it PPMS or SPMS. The use of ocrelizumab in patients with primary progressive MS was shown to have a modest effect: a 20% or 30% reduction in disability progression at 3 months in 20% to 30% of individuals.
There was perhaps some effect from an anti-CD20 monoclonal antibody in individuals with primary progressive MS. That drug and others like it have not been used in SPMS. At least there are no data available yet to suggest that the anti-CD20s are as effective. But there’s no reason to think not.
There have been studies that have subsequently come out that have looked at SPMS with S1P1 receptor modulators like siponimod, which again shows a modest reduction in the progression of the disease as well as an effect on relapses. My sense is that none of the drugs that we have available for us in the treatment of progressive disease are home runs by any stretch of the imagination. At best, they’re singles or doubles if you want to analogize it to baseball. But at least we’re seeing some effect.
In my mind and in reading the literature, where they seem to be most effective, at least in individuals with secondary progressive MS, are in those individuals who are in that transition phase where they still have superimposed relapses and active disease. These drugs are most effective in that context. Unfortunately, we still have a poor understanding of what drives progressive disease and the drugs that target those elements of the immune system that are driving it. What we have available to us is a bit disappointing, but at least we have something.
Bruce Cree, MD: Now that we have something, I’m going to ask Dr Krysko, what do you do when you consider a patient who’s coming in with PPMS or SPMS? How do you determine which of these products to use?
Kristen Krysko, MD: The first factor is whether to start them on a disease-modifying therapy. That comes to what Dr Berger just mentioned. The benefits are there. They’re statistically significantly better than placebo in the trials, but they also have risks. I think especially in progressive MS, where the benefits are not as good as in relapsing-remitting MS, we really need to consider the risk-benefit ratio.
First, I think age is an important factor because younger individuals in the trials have tended to show a better response to therapy. If we have someone presenting with primary progressive MS or converting to SPMS at a young age, that would be a factor that leaves me more likely to recommend treatment. Younger individuals also have more activity. The patients who have gadolinium-enhancing lesions or relapses recently are more likely to benefit as well. That’s been shown in a number of the trials in progressive MS.
Younger age, recent onset of disease, evidence of new lesions, enhancing lesions, or relapses are factors that make me more likely to treat someone with MS who is in a progressive phase. The rate of progression is also something to consider. Even if someone’s not having activity, if you see them getting worse at each clinic visit, it’s hard not to recommend a therapy that may provide some benefit. Whereas if someone’s stable, it’s hard to know if you’re providing any benefit of the treatment.
Other factors I consider are the level of disability and comorbidities. Those increase the risks; some of these medications have risk of infection. If someone is already wheelchair-bound, that risk is even higher and makes me hesitate to start a disease-modifying therapy that’s immunosuppressive.
It’s the same with comorbidities in patients who have diabetes, hypertension, or cardiac disease. They may not tolerate these medications as well, so you need to consider the potential risks and whether you’re causing more harm than good by starting a disease-modifying therapy. Those are some general thoughts about when to start a treatment in someone with progressive MS. I think we’re going to talk about the specific treatments coming up.
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Transcript Edited for Clarity