IJMSC Author Spotlight: Sarah A. Morrow, MD, MS

Sarah A. Morrow, MD, MS, FRCPC, FAAN, was the first author of Wearing-Off Effect Reports in People With Multiple Sclerosis Receiving Ocrelizumab published in the International Journal of Multiple Sclerosis Care (IJMSC) in June 2025.

Sarah A. Morrow, MD, MS

[Image courtesy of the doctor.]

Morrow received her MD from the University of Calgary and completed her residency training in neurology at Western University. She also completed a Master's of Science in epidemiology at the State University of New York at Buffalo.

She is a professor in the Department of Clinical Neurological Sciences at the University of Calgary (Calgary, AB), director of the Calgary MS Program, and co-director of the MS research program.

Dr Morrow recently sat down with IJMSC to talk about the paper, her career path, and her research.

IJMSC: Tell us the story of your paper about the COMPASS program and ocrelizumab [Ocrevus]. Where did the idea come from, and how did you put together the team of researchers and authors?

Sarah Morrow, MD, MS (SM): We had a lot of patients coming in and telling us about this term, crap gap, which was coined on Reddit. It is not a medical term, and we were not aware of it from a medical point of view. Patients brought it to us, saying, “Oh, I’m having this. I’ve read about it.” And we were interested in how often it is really happening, since we also noticed that it wasn’t being reported until they read about it or heard about it from other people with MS. There had been a few studies [that] had [different methods], where they had asked their patients if they had been experiencing the wearing-off effect. These studies often included a very small sample and relied on almost prompting patients [by asking], “Are you experiencing this?”….We thought we’d try and make it a bit more objective with a larger sample….In Canada, because the medication [ocrelizumab] is dispensed and administered at private clinics, not within the hospital system, because of the way the health care is set up, it means it’s administered by a program called COMPASS [Canadian Roche Patient Support Program]. [This] meant we had access to [a majority of] the people in Canada who were getting Ocrevus….It really gave us a comprehensive patient base all across Canada. [Because of the program,] there’s a nurse who works with them every time they get their infusion, who knows them well and always asks about any [adverse] effects they may be experiencing. [That question] gave us a database of people who were spontaneously reporting that they were having this wearing-off effect…between infusions. We were able to collect data over 5 years, and this included all patients who had relapsing or progressive MS who spontaneously reported to their infusion nurse that they were experiencing this wearing-off effect at their infusion center when they were asked about an adverse event. They were asked if they were having any trouble, but they weren’t asked about wearing-off or crap gap specifically. What we found is that very few patients spontaneously reported that they had this wearing-off effect. It was reported in only 140 cases, of which 138 patients were involved…so, out of just over 10,000 patients that were included in this database, only 138 patients reported this wearing-off effect….It was less than 2% of the sample that spontaneously reported, which is much less than what you’ve seen in other studies.

Another Canadian study…where they actually asked their patients, “Are you having a wearing-off effect?” or “Are you having a crap gap?” reported [that] up to 16% of patients were endorsing this. We think that the truth probably lies somewhere in the middle, probably more than 2% because some people would just not think to report that to their infusion nurse, but we do think it’s less than 16%, partly because this is a much more comprehensive sample and also because we think that there is some power of suggestion with these symptoms because they are subjective. [The] symptoms that are reported in the crap gap are things like fatigue, worsening cognition, [and] worsening mood, which are all very subjective and hard for us to quantify as getting worse.

Another interesting thing is that the wearing-off effect did not lead to an increase in discontinuation of the medication. The number of patients who discontinued, of those who reported the wearing-off effect, was the same proportion as the larger group that did not report the wearing-off effect. [Sex], type of MS, how many infusions they’d had—there [wasn’t] any difference between those who were reporting the wearing-off effect vs those who did not.

IJMSC: The term crap gap was coined by patients on Reddit, and they brought it to your attention? Had you ever heard it before?

SM: Patients would come in and say, “Oh, I have crap gap.” I remember the first few times I thought, “What is this crap gap?” The patients are talking about it on social media, but when we Googled it, the only reference we could find to it was on Reddit. Now, it’s possible it was on other social media, like Facebook or Instagram, that I couldn’t [access], but the only reference to the term crap gap we could find was actually on Reddit. When we brought it to the company that makes ocrelizumab and said, “Have you heard about this?” they, of course, did not like that term, and neither do I. It’s a terrible-sounding term. [They said,] “Wearing-off effect is a better descriptor,” and that is so true. We started using that descriptor, although patients still tend to use crap gap.

IJMSC: It’s amazing, the power of social media. What do you want clinicians to take away from this paper and this research?

SM: I think it’s important for clinicians to acknowledge what our patients are feeling, but also talk to them about what this wearing-off effect truly is. This was not part of our research specifically, but other groups have looked at the fact that wearing off doesn’t seem to differ based on B-cell counts or body mass index, which, at some point, was thought [to] have something to do with wearing off. It doesn’t have anything to do with [immunoglobulin G] levels or how advanced their MS was vs new starts, or people who were naive to treatment vs those who may have been switched to Ocrevus because their disease is more aggressive or their previous treatment was not effective. This [data] tell us that there’s not really any good way to predict who’s going to get this, but it also means that we do need to check in and see if they’re truly experiencing this wearing-off effect. We all know that the power of suggestion is a real thing….So it’s really important to counsel our patients that it’s perhaps not as common as we think, and to really see if there’s a way we can objectively measure whether they’re having issues with their drug and if they’re having [adverse] effects. [Frequently,] if we counsel our patients appropriately, we can improve their quality of life because they feel that this is happening. Talking them through it, and validating what they’re going through, but also saying, “It may not truly be happening in the way you think,” may improve their satisfaction with the medication.

IJMSC: What is the 10,000-foot view of this? If we pull back from your specific study, are we talking about subjective vs objective and how clinicians can listen to their patients and validate them, but also offer other alternatives?

SM: All the studies have been subjective; [they] have only looked at what patients are reporting. Even some prospective studies have really only looked at self-reported measures. No one has actually done a study [using] objective measures, such as perhaps the 9-hole peg test time, timed 20-foot walk, neurological exam, or cognitive testing such as the [Symbol Digit Modalities Test]. I think one thing that would be important is to look at your individual patient and consider why they’re experiencing this. The 10,000-foot view is that every patient is an individual, and even though we think it’s less frequent than reported, it still is happening….We still had 2% of patients who said they were experiencing this. It tells us that we need to consider each patient individually and question those who are reporting a wearing-off effect [to] see if we can actually quantify what they’re noticing, and then try to treat the symptoms. But a lot of it may just be education, explaining that this is actually not as common a phenomenon as we think, and in those who are experiencing it, making sure you do address it.

IJMSC: Is there a next step for this research?

SM: I would like to see if we could show that there is some objective change prior to the infusion, but that requires quite a lot of staff that I’m not sure is currently available. I do think it’s important to look at other B-cell therapies, or perhaps other high-efficacy therapies that are given in this timed manner. It would be interesting to see if the same effect happens with the other B-cell depleting therapy, Kesimpta, which is given every 4 weeks. If someone’s experiencing a wearing-off effect, would switching to Kesimpta alleviate it? Or do those people experience a wearing-off effect with another medication that [has] a similar mechanism of action? I think looking at wearing off in general in medications that aren’t given daily would be interesting to see. Is this [occurring]…with ofatumumab or natalizumab?

IJMSC: How did you get involved in MS research? What was your path?

SM: It was through medical school. I worked with an amazing mentor on my very first research project, which happened to be in multiple sclerosis. Her name was Luanne Metz, who’s a bit of a giant in the field of multiple sclerosis, and it was really fun to be able to design a study that you could then see the answer to. I thought that was just so satisfying to say, “We don’t know the answer to this. Why don’t we do a study on it?” [This] was what she did, and then mentored me through the whole process. That’s been what’s guided my research: Is there a question we can’t answer? [An example is] this study where [we ask], “How often is the crap gap or wearing-off effect actually happening?” And then we designed a study to answer that question.

"That’s been what’s guided my research: Is there a question we can’t answer? [An example is] this study where [we ask], 'How often is the crap gap or wearing-off effect actually happening?' And then we designed a study to answer that question."

IJMSC: What is your current research project?

SM: One of the things I’m very interested in is this idea of cognitive PIRA [progression independent of relapse activity]…of cognition worsening, even though people are considered stable on their disease-modifying therapies. We now have these amazing treatments that really prevent almost all relapses and MRI activity, and yet we’re noticing that patients are worsening. It’s really only recently that we were able to show that the inflammatory part of the disease affects cognition. We’re almost now turning the tables back to where we were before and saying, “Why are these people worsening despite good control of inflammation?”

IJMSC: What does multidisciplinary care mean to your practice?

SM: I think multidisciplinary care is very important in a disease like MS. Although our medications are much more effective than they used to be, it still leads to disability. It is a lifelong disease. Once you tell them they have MS, we don’t have a cure, so they’re going to have MS for the next 20, 30, 40, 50 years. Managing a disease like this, which is somewhat unpredictable and lifelong, really needs to involve more than just the neurologist. It really needs to involve nursing care. For example, with our study, the nurses were getting this report from the patients, and without the nurses being part of our team, we wouldn’t have known about it. Also, we need to remember that even though we think of relapses as 1 of the…manifestations of MS, in between relapses, patients may be experiencing disability, and so addressing that disability to improve their quality of life is really important. That could include physiotherapy or social work or counseling, psychology. And my interest is in cognition, so how do the cognitive effects of MS affect day-to-day life? Having neuropsychology involved [allows us to] actually quantify what [patients are] experiencing and then get them into rehabilitation or other things that will help them continue to do what they want to do with their lives. That is so important for our patients living with MS.

IJMSC: Do you have any opinion about AI and its use in care or research?

SM: I think it’s the way of the future, whether we want it to be or not….I am still a bit of a technological Luddite, so I myself am not proficient at it, but I’m always amazed by those who use it. Certainly my colleagues who use the AI apps or the AI tools for dictation have made their lives much more efficient. Having an AI scribe who can summarize the visit and [make sure it’s accurate is helpful] because afterwards, I have to remember what we talked about or what they said. It also gives us the time to see patients rather than doing paperwork. On the flip side, though, we have to be careful because AI is only as good as we make it. I know there have been instances where ChatGPT, for example, spits out information that is incorrect because of the information that’s been put in. They can only take what we give them. We do have to keep in mind that we can’t rely solely on AI because there is still that human factor in medicine. There [are] so many times where it’s not just the diagnostic criteria or the presentation of the case, it’s that feeling you get from taking a history from a patient, it’s that feeling you get when you’re examining them—that you add [value]. It’s clinical judgment and clinical acuity, which I don’t think you can fully replicate with AI.