INDIANAPOLIS – Consider disease activity, patient comorbidities, treatment tolerability, and patient or physician preference when prescribing disease-modifying therapy for multiple sclerosis patients.
“Where I practice, patient preference can sound something like, ‘My sister-in-law’s cousin’s friend at church takes drug X, and that’s the one I’m interested in,’ ” said Dr. Myla D. Goldman, a neurologist who directs the James Q. Miller Multiple Sclerosis Clinic at the University of Virginia, Charlottesville. “It’s sometimes guided by just familiarity or word of mouth, or something that they’ve read or someone that they know. In terms of our own preferences as clinicians, those are much harder to characterize. I think they become shaped over time and our own experiences, as well as being guided by evidence-based medicine.”
Dr. Myla D. Goldman
In a survey, 102 neurologists were asked about how they made decisions regarding the prescription of disease-modifying therapies (DMTs) for patients with MS (Patient Prefer. Adherence 2014;8:415-22). More than 80% ranked efficacy as the most important attribute of DMT medication selection, followed by safety, tolerability, patient preference, and convenience (including dosing frequency and administration method). In a separate study presented at the 2014 meeting of the American Academy of Neurology, 1,628 MS patients in Germany were asked about the importance of different DMT features (Neurology 2014;82[10 Suppl.]:P3.137). They ranked oral administration as the most important attribute in guiding their DMT preference, while the second most relevant attribute was frequency of administration.
In a more recent study, 50 patients with relapsing-remitting MS were asked about their preferences for attributes of DMTs (Int. J. MS Care 2015;17:74-82). Survey respondents showed the highest preference for medications that would improve their symptoms, which is not a proven DMT outcome. Preventing relapses, which is a key clinical trial outcome, was not associated with significant preferences.
“This is important to know but adds another layer of challenge and complication [because] what we understand most about many of these agents is their effect on relapse rates,” Dr. Goldman said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “It’s another disconnect in terms of what we’re thinking about, the tools that we have, and where our patients are coming from.”
Other factors to consider when selecting a DMT include disease activity/burden, risk/prognostic factors, treatment safety/tolerability, comorbidity, and treatment access/logistics. “As we’ve had more and more [DMT] choices available to us, we’ve become more restricted in how we make choices – which patients can have what choices in what order,” she said. “This is a reality that we all have to face but is something that varies from third-party payers and region, and can be really complicated to navigate.”
In general, Dr. Goldman continued, it’s recognized that more active disease requires more effective therapies with greater tolerance for risk. However, evidence suggesting that early disease activity predicts long-term outcome is poor, “not because it may not be true but because we don’t have as robust data as we would like,” she said. “We also have few [clinical] trials focused on this group. So when we look at high disease activity, it’s typically in a subgroup analysis. There are risks for underpowering and a lack of direct comparisons among therapies. I have found that my idea of disease activity and my individual patient’s idea of disease activity sometimes differ. Perhaps I think we need to make a change, and they feel comfortable with what they’re taking, or vice versa.”
There are various predictors of disease activity and outcomes based on early signs and symptoms, “but these outcomes are variable when we are comparing across studies,” she noted. These predictors and outcomes include:
• Early disease activity predicts relapse disease activity early, especially with posterior fossa lesions and enhancing lesions.
• Early MRI activity predicts long-term disability.
• A baseline T2 lesion burden predicts change in the Kurtzke Expanded Disability Status Scale (EDSS) and progression to secondary-progressive MS.
• A T2 lesion change at 1 year predicts EDSS change.
• Brain atrophy over 2 years predicts EDSS at 8 years.
Favorable prognostic factors include monofocal onset, onset with optic neuritis or isolated sensory symptoms, younger age at onset, being white, being female, having a low relapse rate in the first 2-5 years, and a long interval between the first and second relapse. “That’s where early treatment and impact on relapse rate has a really important role,” she said.
Unfavorable factors in relapsing-remitting MS include multifocal onset, being black, older age at onset, being male, high relapse rate in the first 2-5 years, disability at 5 years, cognitive impairment, high MRI lesion load at baseline, atrophy and T1 holes on MRI, and being a smoker.