IJMSC Author Spotlight: Katherine Knox, MD, FRCPC

Author Katherine Knox, MD, FRCPC, was the first author of Physical Activity in Multiple Sclerosis: Real-World Data From Saskatchewan, Canada, which was published in the International Journal of Multiple Sclerosis Care (IJMSC) in February 2025.

Katherine Knox, MD, FRCPC

[Image courtesy of the author.]

Knox is an associate professor in the University of Saskatchewan's Department of Physical Medicine and Rehabilitation, as well as the provincial department head. She is also a clinical investigator with the Cameco MS Neuroscience Research Center at the University of Saskatchewan and the MSCanRehab Network, with a focus on gait, exercise behavior, long-term outcomes, and quality of life for people with multiple sclerosis. Her clinical practice includes neurorehabilitation services, with a special interest in multiple sclerosis. Her fellowship training was done in physical medicine and rehabilitation at the University of Saskatchewan in the mid-2000s, and her degrees were completed at McMaster University.

She sat down with IJMSC recently to discuss the approach to the paper and its findings, her career path, and her research.

IJMSC: Tell us the story of this paper. Where did the idea come from, and how did you form the team of authors?

Katherine Knox, MD, FRCPC: The story actually started [with] Dr Walter Hader Sr. He established one of the first multidisciplinary clinics in Canada back in the 1970s, and he was meticulous with data collection, real-world data collection. Then, in 1997, when we were able to access Betaseron—the first disease-modifying [DMT] treatment for MS [multiple sclerosis]—in Saskatchewan, the minimum data set expanded and an infrastructure for real-world data collection was set up in partnership with the Ministry of Health.

Because of that long-standing partnership and infrastructure, when the first physical activity guidelines were published in 2013, [they] allowed us to fairly quickly add physical activity data to the data that we were collecting in a real-world setting of people accessing disease-modifying therapies in Saskatchewan. Those first guidelines for physical activity in MS were published by Amy Latimer and Kathleen Martin Ginis and [their] team in 2014. We decided to add the Godin Leisure-Time Exercise Questionnaire to collect physical activity behavior data.

It was pretty easy to bring the team together because we had some people who were really interested in MS here at the University of Saskatchewan. [Charity] Evans completed her postdoc at UBC [University of British Columbia] in MS pharmacoepidemiology, and she had joined [the] faculty, so she was a natural fit to join the team and help us analyze these real-world data, along with Sarah Donkers, who completed her PhD in exercise behavior and people living with MS [in] the US, so she was also a natural fit. And then we reached out to the Clinical Research Support Unit for some statistical support for the analytical portion, and we were really pleased to have a great team that joined us, along with a master’s [degree] student from their group. So that’s how the team came together, and that’s how the story started.

IJMSC: What about this research was surprising to the team of authors?

Katherine Knox, MD, FRCPC: There were actually 3 things that surprised me. The first is that we did not observe a statistically significant trend in physical activity levels over the 7-year data collection. The second was that prior DMT exposure was not associated with physical activity levels, and we had hypothesized that it might be. And the third was that there was quite a bit of fluctuation year to year in the proportion of people who met the threshold of activity level [that was] significant for substantial health benefits.

From all three of those points, I think there are some take-home messages. The first is this difference between statistical significance and clinical significance. Although we didn’t see a statistically significant finding, we did see that the physical activity levels are trending in the right direction. Over the 7-year span, it would be an average of about an additional 15 minutes of moderate physical activity over the course of a week. It’s not going in the wrong direction, which is good.

In terms of the fact that prior DMT exposure was not associated with physical activity levels, I think this is really important, because when people start a disease-modifying treatment, they’ve had a touch point with the health care system. They’ve had an opportunity for us to at least screen and try to intervene with health behavior modification. One would hope that if they touch the health care system for their DMT treatment, they’ve also had an opportunity to address their health behaviors, and we did not find that to be the case. So that’s really an opportunity there.

The third point about the fluctuation year to year in terms of the proportion of people who were not significantly active for health benefits: We saw quite a large variation, between 35% to 60% year to year. I think it just really highlights the point that you can see variability year to year, and if you only have several points or time points of data collection, you don’t really get an idea of what’s happening over time. You really need that prolonged period of time to see if there are changes in behavior in real-world data. Those were 3 things that stood out for me.

IJMSC: Do you have any comment on the difference between the physical activity recommendations vs your findings with the real-world implications? Why is there a disconnect there, that people with MS and clinicians aren’t acting on the recommendations?

Katherine Knox, MD, FRCPC: Recommendations are important. We did see, right after the recommendations were published—in the year following—we did see a little blip, or a little increase. But then it wasn’t sustained. Whether that was associated with that publication or not, we can’t tell, but I think the point is that we need more than recommendations. We also need the infrastructure to implement the recommendations, which is really critical. The 2020 updated physical activity recommendations recommend that a person should be connected with an exercise specialist in MS early on in the disease course, either a physiotherapist, an occupational therapist, or an exercise specialist who has some background in multiple sclerosis. The challenge is that in many of our health care systems, those people are difficult to find or they’re taxed out doing other things. It’s a starting point to have those recommendations, but we also need the infrastructure to deliver them.

IJMSC: If there was only one takeaway from your paper, what would you want clinicians to have learned or have in their heads after they read your paper?

Katherine Knox, MD, FRCPC: The most important thing is to recognize that there is still a subgroup of people, approximately two-thirds, who are insufficiently physically active for health benefits. At the very least, I think clinicians should screen for that group of people and then, as per the guidelines, refer them to somebody who can help them change their health behaviors to become more physically active. If there aren’t support people to help them do that in your system in which you work, advocate to have those resources put in place.

IJMSC: Do you have anything to add about the potential clinical impact of the paper and what you would like to see come from it?

Katherine Knox, MD, FRCPC: We don’t yet have a really clear, validated way to screen. The current physical activity guidelines are for 150 minutes per week of moderate-intensity physical activity or lifestyle physical activity—moderate meaning that you can talk but you can’t sing while you’re doing the activity. Conceptually, we don’t think in 10-minute intervals, so 150 minutes per week [was] actually hard as a screening question. I think we need to look at different types of screening questions, such as, “Are you moderately active for less than 45 minutes a week?” That’s the subgroup who is really insufficiently active, and they’re the ones who are likely to reap the most health benefits. Targeting that population is really important with a screening question that identifies that subgroup.

IJMSC: What do you think the next lines of this research are? Is that a new screening tool or a new validated measure?

Katherine Knox, MD, FRCPC: Really, the research needs to focus on the cost-effective, systemwide supports that we can put in place over the disease course for physical activity. I’m hopeful that the screening part will be relatively simple by just adjusting the screening question slightly to target that most at-risk population. In terms of those systemwide interventions, it’s having those people trained and available to help people, over the disease course, modify the activity so that it’s feasibly practical and convenient for them to do as they age with MS, starting early in the disease course.

IJMSC: Is that your current area of research, or what else are you currently working on?

Katherine Knox, MD, FRCPC: We only have about 1.2 million people in Saskatchewan and a very high prevalence of MS: about 313 per 100,000. That’s about 3500 people living with MS. What we are working on is, if we do implement effectively a systemwide approach to change health behaviors and people living with MS, because it’s a relatively small population, although it’s diversified across a large geographical area, I would like to be able to see that trend that we saw in this paper become statistically significant and see physical activity behaviors continue to change over the longer term. We’re continuing to collect longitudinal, real-world data on physical activity, and we’re working with partners to implement system supports to remain active.

One of the programs that we started in the pandemic is called NeuroSask: Active and Connected, in partnership with MS Canada, the Saskatchewan Health Research Foundation, and other partners. This is a virtual online program that targets any person living with MS. It’s done seated, so a person doesn’t need to be ambulatory to participate. We’ve also piloted an individualized physical activity coaching support program for people living with MS, and what we would really like to do is to increase the scope of that project to reach a greater number of people because it was successful in targeting those people at highest risk for adverse health outcomes in the lowest bracket of physical activity levels.

IJMSC: Where did your systems view come from?

Katherine Knox, MD, FRCPC: It’s a value-based perspective. I really believe that it takes a community to raise a healthy child, and I feel the same way about health care. We can’t just work in silos. We need to look at the whole system. When you do make a system change and you see that it’s been really helpful, it just adds fuel to the fire that you want to make more such positive changes.

IJMSC: Can you give us the 10,000-foot view of how this line of research fits into the larger world of MS care?

Katherine Knox, MD, FRCPC: In the big picture, health behaviors are critical for optimizing health outcomes and function in MS. We know that the high-efficacy disease-modifying therapies, in particular, have really reduced the risk of relapses that are associated with disability, but we have not delivered a product that helps alleviate some of the comorbidity that’s associated with maladaptive health behaviors in MS. I think that we can deliver a health behavior intervention product that could have a significant impact on health outcomes by addressing those modifiable comorbidities with health behaviors, such as hyperlipidemia, hypertension, diabetes. We know that approximately one-third of people living with MS have at least one vascular comorbidity, and that’s associated with more rapid disability progression. We have these very costly disease-modifying therapies for which access to treatment, at least in Canada, is often quite good, but access to support for health behaviors is still a huge gap. I think we can expect, in the 10,000-foot view, to continue to see improved health outcomes if we target this in a more systematic way.

And by a product, I mean to deliver a service that is integrated within our health care system. For example, if you are diagnosed with MS today, you’re referred to a multidisciplinary clinic but you’re not necessarily connected with a coach or a person who has expertise in physical activity or other health behaviors for best health outcomes. That’s what I mean by product—a product that can reach the population but also is individualized to that person’s need, targeting the people who are at greatest risk, who are the most sedentary. When we talk about disease-modifying therapy, we’re targeting those people who have disease activity on MRI. We need to have a targeted approach for people who struggle the most to be physically active.

IJMSC: One of the pillars of IJMSC and the Consortium of Multiple Sclerosis Centers is multidisciplinary care. How do you see research and care working together to improve lives of people with MS?

Katherine Knox, MD, FRCPC: The physical activity recommendations are an excellent start toward promoting that multidisciplinary piece in terms of early referral to an exercise specialist, and I think the research is really about developing the pathway and the product to do that cost-effectively. That is a multidisciplinary ambition.

We can do a better job at showing that this is cost-effective in the longer term by collecting long-term, real-world data. Although we didn’t look at health outcomes specifically—we didn’t look at survival or disability levels—we have the infrastructure that we could expand on that and look at that, and I think others could as well.

IJMSC: How did you get involved in MS research?

Katherine Knox, MD, FRCPC: Well, I got interested in MS by meeting people with lived experience as a medical student volunteering for MS Canada, and I got involved in MS research early in my residency training. I had an opportunity to go to a conference where Dr [V.] Wee Yong and Amit Bar-Or were cochairing this conference, and I was really inspired by how much there was to still understand about MS and by their passion for the work that they did. That really was instrumental in getting me going, both working with people with lived experience early in my career and then having some really wonderful role models to bring me along into the field early on.

IJMSC: Has your focus always been physical activity?

Katherine Knox, MD, FRCPC: I was initially interested in mobility, so I started off doing some work in gait in MS, and I’ve done some work in health-related quality of life. But yes, then I got more and more focused on the physical activity piece.

IJMSC: Do you have any opinion about artificial intelligence (AI)? Was there any AI used in your paper?

Katherine Knox, MD, FRCPC: There was not any AI used in my paper, but I asked AI about the use of AI in research and clinical care, and it was quite biased toward how useful it could be. Just reflecting on my own answer to that question—not what AI told me—I think AI will be useful for allowing faster synthesis of research findings for reviews and so on, and that will help us hopefully close the research-to-practice gap faster. I actually think that human error is still a big problem in everything that we do, and so I guess I’m a little hopeful that AI will be able to help with that human error piece. I do use it every day now to ask questions where I can get quick answers that I used to Google—not even so much for my professional life but in my personal life. You know, “Who won the Jays game last night?”

IJMSC: Anything else you would add about your paper and the future direction of this research?

Katherine Knox, MD, FRCPC: The other thing that I would like to add is that in terms of future directions, I don’t think we need more clinical trials about physical activity in MS. We know physical activity improves function, and it improves symptoms if done at the right dose. We know that it’s beneficial, and we know that all types of physical activity are beneficial. It’s really about which activity a person will do.

We need to spend our resources on that implementation piece. How do we implement physical activity support within our health care systems and within our communities, rather than another randomized clinical trial on physical activity in MS? Those are expensive and costly, and we already know that physical activity is beneficial—the return on the investment is greater to target the people who are sedentary and insufficiently active than it is to try to take people who are already interested in changing their behavior and put them in a research trial.

IJMSC: In MS, it seems like one of the big themes of the day is that the earlier we intervene, the better, whether it’s with DMT, physical activity, rehabilitation, or prehabilitation. Would you say that we don’t need to prove that as well?

Katherine Knox, MD, FRCPC: In terms of cost-effectiveness research, I think the early intervention is something that is important. My hypothesis would be it’s probably a lot like smoking, where it’s never too late to quit, it’s never too late to start. I don’t think that we need trials to look at the early intervention, but I think we could look at real-world cost savings. What happens when you implement a program or a service early over the course of the next 15 years compared with the 15 years prior, where you didn’t have an early intervention product?