February 23, 2024 | News | Living with MS MS Research MS Treatments

MS: the coming (r)evolution (Part 5)

Neurologists currently keep track of multiple sclerosis using various tests and procedures, such as a lumbar puncture (spinal tap), a neurological exam and magnetic resonance imaging (MRI). These provide ‘objective’ findings of ongoing immune response in the central nervous system, nerve impairment, and inflammatory lesions and tissue damage in the brain and spinal cord.

However, that approach captures only part of the story. Much of the day-to-day reality of MS is subjective. Neurologists must rely on people to report their relapses or other symptoms, many of which (e.g. fatigue, pain) are undetectable with medical testing. The need to understand a person’s experience with MS set the stage for the revolution to come: using patient-reported outcome (PROs) measures to provide a more nuanced view of the changes that occur in MS (Zaratin and colleagues. Mult Scler Relat Disord 2022; 61:103757). This is an advance on the former notion of ‘patient-centric’ care, i.e. attempting to accommodate people’s needs with respect to drug choice, symptom management and other aspects of care. The hope is that PROs will enable doctors to provide patient-specific (i.e. individualized) care.

PROs are defined in different ways. The European Medicines Agency (EMA) defines PROs as “any outcome evaluated directly by the patient him/herself and based on the patient’s perception of a disease and its treatment(s).” The U.S. Food and Drug Administration (FDA) defines PROs as “any report of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else”. The difference between these two is that the EMA only looks at active measures, such as a person recording their symptoms or filling out a fatigue questionnaire. The FDA also includes passive measures, such as wearable devices (e.g. Apple watch, Fit Bit) that gather health data (often without you knowing).

PROS can help people achieve two quite different goals. The first is to identify subtle changes (e.g. symptoms, worsening ability, cognitive difficulties) that may not be detected by a doctor, but which may herald that MS is getting worse. Predicting the course of MS largely relies on group-level data (i.e. studies of populations), which may not be that accurate for the individual person with MS since a person’s MS is influenced by their genetics, environmental exposures and other factors. PROs may help to refine the picture of MS in a given person and serve as an improved early-warning system to prompt a change in treatment to something that will be more effective. PROs are now being used in clinical trials – a trend that will increase in the years ahead – although the rationale and selection of specific PROs still needs to be sorted out (Hobart and colleagues. Mult Scler Relat Disord 2023:76:104788).

The second goal is more ‘health consumerist’: to use PROs to improve treatment satisfaction and quality of life. A common complaint among people with MS is that the benefits treatment can deliver and the benefits actually people want are not always aligned. PROs may help to close that gap. At the very least, PROs may heighten awareness of the symptoms people are experiencing.

At present, there are dozens of PROs from which to choose. Some are questionnaires, such as the 29-item Multiple Sclerosis Impact Scale (MSIS-29) (https://mstrust.org.uk/sites/default/files/MSIS-29.pdf), or the MS Quality of Life Inventory (MSQLI), which comprises 10 different questionnaires (www.nationalmssociety.org/For-Professionals/Researchers/Resources-for-MS-Researchers/Research-Tools/Clinical-Study-Measures/Multiple-Sclerosis-Quality-of-Life-Inventory-(MSQL). Some PROs ask people to rate their function, such as the Patient-Determined Disease Steps (PDDS) (www.nationalmssociety.org/NationalMSSociety/media/MSNationalFiles/Brochures/10-2-3-28-Disease_Steps_Form.pdf). These questionnaires are typically scored and interpreted by a doctor.

There are several important limitations with PROs. Studies must be done to validate the questionnaires to ensure that they are recording something meaningful. For example, a recent study found that most of the PROs that were used (assessing fatigue, depression, health perception, etc.) did not predict disability (Abbadessa and colleagues. Mult Scler Relat Disord 2023;75:104731). Questionnaires collected after the fact can suffer from recall bias (What symptoms got worse when I had that relapse four months ago?) so they may not reflect what is going on. And it is not always well understood what a PRO is actually assessing. For example, a recent study compared a person’s assessment of their disability (using the PDDS) with a neurologist’s assessment (using a scale called the EDSS) (Foong and colleagues. Eur J Neurol 2024;31:e16046). Both of these scales gave some sense of worsening function – but they did not appear to be measuring the same thing.

PRO data can also suffer from ‘response shift’, i.e. people get used to a problem, so they tend to score it as less severe over time. This phenomenon was seen in an analysis of a Tysabri trial, which found that how people scored their ability over time inconsistently reflected the worsening disability they were experiencing (Strijbis and colleagues. Mult Scler 2022;28:1606-1619). People can forget how they felt six months or a year ago.

The next-generation PROs will be digital. For example, smart watches can now record heart rate, step count, exercise duration and intensity, oxygen level, body temperature and other metrics. Personal data may be helpful (e.g. to prompt activity or record exercise goals). But it remains to be seen how these and other measures relate to MS, and whether these data can be used to identify people at risk of getting worse. The challenge for healthcare providers will be to synthesize, interpret and use these data. Efforts are now underway to validate smart watch-based applications that evaluate balance and gait changes in people with MS (Rinderknecht and colleagues. Digit Health 2023; epublished October 19, 2023).

Perhaps the most promising use of personal biometrics will be to combine it with data from digital tools being developed for doctors. These can evaluate eye tracking (as a measure of nerve damage), limb function, fatigue, cognition, speech impairments and a host of other things.

What this growing array of tools can offer is a more finely-grained assessment of day-to-day changes in an individual person’s life. Not all fluctuations will be important. But they will give a more complete view of that person’s MS and provide a firmer foundation for that person’s individualized care throughout the lifelong course of the disease.

Part 4, Part 3, Part 2, Part 1

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