Personalized medicine is just about the biggest buzzword in health. But neurologist Ellen M. Mowry, MD, of Johns Hopkins University, Baltimore, steers patients with multiple sclerosis (MS) away from the concept when she first starts talking to them about initial therapy options and possible ways to forestall disability down the line.
Dr. Ellen M. Mowry
“I try to be quite honest,” she told colleagues at the 2021 Annual Meeting of the Consortium of Multiple Sclerosis Centers (CMSC).
Observational and clinical trials offer extremely limited insight, she said in a keynote address, so there aren’t any simple answers about the best strategies. However, she highlighted new research projects that aim to provide more reliable answers.
As Dr. Mowry noted, patients tend to do well early on regardless of the choice of drug, so the question isn’t how to immediately control MS. “I personally find that most people can have control of relapses and the development of new lesions. I don’t find that there are too many individuals these days who don’t achieve control of their inflammatory activity,” she said. “I’m really interested in understanding whether the treatment choices a person with MS and myself make – at the time of their diagnosis – matters with respect to how they’re doing several years down the road. One major question is: Should I be using higher-efficacy therapy right out of the gate to better impact long-term disability?”
Research suggests that disability in MS is declining dramatically, she said, although it’s not quite clear if this is caused by evolving definitions of the disease or better medications. If the latter is the case, it’s useful to know that “there have been several publications suggesting that using stronger therapies right out of the gate may have an even greater impact on the long-term disability trajectory [than lower-efficacy treatments],” she said.
But some studies in this area are observational and come with various weaknesses, she said. Clinical trials offer data of their own, but “the conditions of clinical trials are also not real world or generalizable.” They often have healthier subjects than physicians actually see, and their requirements – such as requiring patients to have failed certain therapies – can muddy the messages of their outcomes. And, she added, people are more complicated in real life than in these trials, with many having a mix of both higher- and lower-risk features.
So how can physicians make the best decisions? Dr. Mowry recommends considering several factors, such patient comorbidities and reproductive status, the way drugs are administered, monitoring requirements, and cost. Safety is crucial too. She noted that newly diagnosed patients with MS are very concerned about safety – “they’re very much afraid of risks of stronger medications” – and many choose escalation therapy instead of immediately embracing higher-efficacy therapy for that reason.
At her clinic, she doesn’t push quick decisions. “I find that the treatment-decision discussion with individuals with MS takes several appointments, which we offer typically in quick succession. If we go with the escalation route, we are very strongly conscientious about escalating if there’s breakthrough disease. For me, that means after the medication should have kicked in, we may indeed escalate that therapy right away if there’s a new relapse or more than one new lesion.”
As for the future, Dr. Mowry highlighted two ongoing clinical trials that are expected to provide guidance about first-line therapy options. One is TREAT-MS, which will track intermediate-term risk of disability based on choices regarding first-line and later therapy. The pragmatic trial aims to enroll 900 subjects for up to 5 years. The other is DELIVER-MS, which aims to track how treatment choices affect brain volume.
“We really do need more definitive data to support the early treatment choices that people need to make,” she said.
Dr. Mowry disclosed grant/research support from Biogen, Teva, and Genentech, as welll as honoraria (editorial royalties) from UpToDate.