Neurology Mastery in Multiple Sclerosis: Focusing on Quality-of-Life

Bardia Nourbakhsh, MD on predictors of quality-of-life in early MS

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Bardia Nourbakhsh, MD

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Action Points

  • Baseline severity of fatigue and depression predicted subsequent changes in physical components of health-related quality of life (HRQoL) in a small study of patients with early multiple sclerosis (MS).
  • Note that quality-of-life was measured by Short Form (SF) 36, which examines eight different areas of health including physical and mental components of quality-of-life, and is used for many different diseases and conditions.

Bardia Nourbakhsh, MD, is an assistant professor of neurology at Johns Hopkins University in Baltimore. His research interests focus on pathophysiologic mechanisms and therapeutic targets in multiple sclerosis-related fatigue. He spoke to MedPage Today at the American Academy of Neurology’s annual meeting in Boston.

Following is a transcript of his remarks.

Click here to download the poster.

This is a study me and my colleagues did when I was a fellow at UCSF. The title of the study is "Fatigue and depression predict quality of life in patients with early multiple sclerosis," and it's a longitudinal study. Fortunately nowadays, we have many, many different treatments that target the disease activity in patients with MS, specifically relapses and MRI disease activity. However, the studies that look at the efficacy of those treatments, although they probably measure quality-of-life, but those measures are probably secondary or tertiary measures, and not much attention is being paid to those results, and regulatory agencies probably do not pay attention when they're trying to approve or assess the efficacy of those medications.

Quality-of-life is pretty important in other of areas of medicine – for example, cancer – and is also a big issue in patients with chronic neurological disorders such as MS. I thought that now that we have many treatments for relapses, maybe we'll pay more attention to other aspects of the disease. Fortunately, many, many researchers are attending progression in multiple sclerosis. Again, I thought quality-of-life is something that's less studied, so I thought that would be a good area to study basically and that would be very helpful for patients and families that are affected with multiple sclerosis.

Basically, I used the data that was accumulated during a clinical trial. The clinical trial was done by Dr. [Emmanuelle] Waubant, and the primary objective of the clinical trial was looking at possible neuroprotective effects of a medication that we use for another neurological disease, specifically amyotrophic lateral sclerosis. The medication is called riluzole, and my mentor wanted to assess the efficacy of riluzole in slowing down brain atrophy as a possible biomarker of the disease progression in MS. Long story short, the primary outcome was negative. Riluzole didn't show any effect on brain atrophy or any other outcome -- primary, secondary, and tertiary outcomes -- that we looked at.

But during this three-year study, a very good data set was accumulated from longitudinal measurements of many different outcomes, including clinical outcomes, cognitive outcomes, MRI outcomes, and quality-of-life. So, I thought it would be a good opportunity, now that the primary outcome was negative and the drug didn't show any effect, looking at these other outcomes and see if we can see associations between, for example, cognitive outcomes, MRI outcomes, and the quality-of-life.

So 43 patients were recruited in the study. Half of them were assigned to riluzole, half of them were assigned to placebo. But because there was no effect of riluzole on any outcome, I combined both groups to look at these associations. Patients were followed between 2 to 3 years and they were assessed at baseline, and very frequently, depending on the outcome. For example, cognitive outcomes were assessed every year at baseline, year 1 and year 2, and half of the patient year 3.

Some other outcomes -- for example, disability outcomes -- were assessed more frequently at baseline t0 month 3, month 6, month 12, month 24, and month 36. So, I used this rich data set using longitudinal analyses, looking at the association of quality-of-life as my outcome and trying to see if, for example, physical disability or cognitive dysfunction, or fatigue, or depressive symptoms, any of those affect the quality-of-life in a longitudinal analysis.

Many previous studies have looked at these outcomes and these associations on a cross-sectional basis. But we know longitudinal studies have higher value in terms of having or showing us probably causality further, as opposed to just mere association.

Quality-of-life in the study was measured by Short Form 36. It's not a measure that is specific for MS. It has been used for many different disease and conditions, and it examines eight different areas of health. It both assesses physical quality-of-life, physical components of quality-of-life, and also mental components of quality-of-life. Actually, there are methods to summarize those eight components into two big physical component and mental component summaries.

I used this physical component summary and mental component summary as my outcomes in the models that I used. As predictors, we had physical disability measured by EDSS, Multiple Sclerosis Functional Composite (MSFC). Both have been used very frequently in different clinical trials of MS. Another predictor was depression. PHQ-9 was used as a measure of depression during this trial. Fatigue was measured by MFIS (Modified Fatigue Impact Scale). That's the most commonly used and commonly actually recommended measure of fatigue and MS. And cognition was actually assessed by five different tests that assess different domains of cognition. They were administered very frequently at different time points during the study.

Interestingly, I used both the baseline severity of my predictors as predictor of the outcome and I also used the longitudinal changes of these predictors as the predictor of the outcome. What we found was the baseline severity of fatigue and depression actually predicted the subsequent change of the physical components of SF-36. Also, changes in the disability as measured by MSFC, and depression over the period of the study, was associated with change in the physical component. So, both fatigue and depression, and also disability, were associated with physical components summary change of the quality of life. Considering the mental components ... we found that changing cognitive function and fatigue were associated with this outcome.

We think that we had a pretty frequent and systematic measurement of both clinical and cognitive outcomes during the study. Our cohort of patients was a homogenous group of patients with early MS. We used a pretty robust statistical method and we mutually adjusted for all the predictors in our models.

As a limitation, you can imagine that our sample size was not very big and we did multiple comparisons, which increases the possibility of false findings, basically. As you notice, fatigue was kind of a common denominator affecting both physical and mental component summary of quality-of-life, and these are patients with very early MS, actually. They have minimal disability, if any, and as we know fatigue is extremely common in MS. It's probably one of the most common symptoms, if not the most common, and as you saw, we demonstrated that even in patients with early disease it affects the quality of life. So, we think addressing fatigue would be a greater step, a bigger step, in improving quality of life in patients with MS.

Unfortunately, we don't have good pharmacological treatment for fatigue. All the medications that we use either do not have any evidence in the literature or have minimal evidence of efficacy. The literature actually recommended that we need further evidence if any one of these medications that has been commonly used worked in MS.

So, based on this background, we actually applied for funding and received funding from the Patient-Centered Outcomes Research Institute (PCORI) to compare the efficacy of three of the most commonly-used medications for fatigue and MS in the clinical practice -- specifically amantadine, modafinil, and methylphenidate. We use them very frequently in the practice, but as I said, we don't have very good evidence that any one of these medications work. Or if they work, which one works better? So, doing comparative effectiveness trials, we will try to answer those questions.

I think the biggest takeaway is we saw that fatigue, depression, cognitive changes, and physical disability all affect different aspects of quality-of-life in patients with early MS. Even in patients with early MS, with minimal disability, these components, these factors, affect their quality-of-life. And probably addressing those ... for example, maybe we can't do much about cognitive changes nowadays, but fatigue, depression probably are treatable, and addressing those issues could probably improve the quality-of-life for patients with MS.


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