Jessica Walsh, MD, on Medication Wear-Off in AxSpA: Part 1

In the first part of this 2-part podcast, Dr Walsh discusses her study on patient perspectives and experiences with medication for axial spondyloarthritis, including loss of efficacy between doses.

Jessica Walsh, MD, is an associate professor of rheumatology at the University of Utah and section chief of rheumatology at the Salt Lake City Veterans Administration Medical Center. She is also a medical advisor to CreakyJoints.

Listen to part 2 of this podcast here.

TRANSCRIPT:

Welcome to this podcast from the Rheumatology and Arthritis Learning Network. I'm your moderator, RALN, and I'm very pleased to have as a guest today, Dr. Jessica Walsh, who is an Associate Professor of Rheumatology at the University of Utah and the Section Chief of Rheumatology at the Salt Lake City Veterans Administration Medical Center. She's going to talk with us about a recent study into patient experience and perceptions relating to the wear off of biological DMARDs in the treatment of axial spondyloarthritis.

Rebecca Mashaw:

Thank you for being here with us today, Dr. Walsh.

Dr. Jessica Walsh:

It's my pleasure.

Rebecca Mashaw:

What led you to do this study? What interested you in finding out about patient experiences and perceptions regarding the diminution of the effect of biological drugs for patients who are being treated for axial spondyloarthritis?

Dr. Jessica Walsh:

My experience is with patients in clinics primarily, so a lot of patients express their concern or experience with feeling like the medication effect doesn't last the whole time between their doses and their frequent request to increase the frequency of their dose or otherwise get help to manage those symptoms in the last days or weeks before their next dose is do.

Rebecca Mashaw:

What biologics were being used to treat these patients?

Dr. Jessica Walsh:

Pretty much, we looked at everything that was available and in use and approved by the FDA at the time of the study. So mostly TNF inhibitors and IL-17 inhibitor.

Rebecca Mashaw:

No JAK inhibitors?

Dr. Jessica Walsh:

Yeah, we didn't have as much data with them so we really restricted this one to biologics. In the future, I think that will change.

Rebecca Mashaw:

Did you find differences between the degree of wear-off based on which drug a patient might be on?

Dr. Jessica Walsh:

Yeah, so we looked at that in a fairly preliminary way, meaning the study wasn't powered, or we didn't have enough people with each of the different specific biologics, to statistically conclusively say that it's different with this drug versus this drug, but we did kind of take a preliminary peak. And my impression of the data so far is that the medications that have longer intervals between dosing, so some of the medications that are dosed every eight weeks or even every four weeks as opposed to medications that are dosed weekly or every two weeks, seem to have more of an issue with wear off, as in a higher percentage of patients said they struggled with the wear off with those longer dosing medications.

Rebecca Mashaw:

Was there any difference in terms of the mode of administration?

Dr. Jessica Walsh:

That's a little bit of a tricky question because the IV mode of administration tends to be the medication with the longer interval. So I'm not sure if that's related to the dosing interval or the mode of administration.

Rebecca Mashaw:

Your research indicates that about 61% of the patients you surveyed perceived that they had some wear off of their biologic DMARD prior to their next scheduled dose. Were there specific symptoms that came on more often with these patients? Was it pain? Was it disability? What were they experiencing?

Dr. Jessica Walsh:

Yeah, so in terms of understanding what specific symptom occurred in the days or weeks before their next dose, we don't have very detailed information with that, but we do know there were some groups of symptoms or sets of symptoms that were more frequently associated with wear off. So people who experienced the wear off, statistically, they were associated with worse physical function, worse sleep, higher pain, particularly higher pain that was interfering with their life, and then their overall disease activity of their axial spondyloarthritis. So it looks like there were a broad range of symptoms that were likely associated with or experienced by a patient who experienced the wear off.

Rebecca Mashaw:

Did your research give you any insight into why this is happening? Is it a matter of inaccurate dosing, pharmacokinetics, type of medication? Anything else?

Dr. Jessica Walsh:

This is a fantastic question, and I think this is what we need to study next. We really don't know why. We don't know if some people are metabolizing the drug more quickly than others, or if some people are underdosed, or if there are other phenomena that are occurring to make this wear off occur. There's a lot that needs to be researched there to understand that question, particularly when we look at it with respect to what's seen with clinical trials. So several biologic manufacturers have looked at different dosing schedules, and some of the data in those trials has suggested that the longer dosing is as effective as the shorter term doses, but that's not what we're seeing in clinical practice. And it's not just the study and our experience, it's a recurrent theme that we hear over and over again, that patients are saying their medications are wearing off prior to the next dose. So fascinating question and a little bit of disconnect with the type of data that we have so far.

Rebecca Mashaw:

Is this the difference between the controlled atmosphere of a clinical trial and the real world experience of patients who aren't carefully selected for certain characteristics?

Dr. Jessica Walsh:

Yes. I'm glad you asked that question because that is a very relevant and widespread issue that we have with research with these medications. So the clinical trials, like you said, those patients are a little bit of a narrower spectrum of the overall population of people who experience this disease. And so people who look just like those patients that are in the trials, we can say, "Gosh, we expect you to respond the same way patients do in the trials," but in the real world, a lot of patients don't look like them. And so it may be exactly what you just said, in that when we look at all those other patients who don't look exactly like those clinical trial patients, there's differences, differences in their diseases, differences in the patients, differences in their clinical settings and how they're treated and how closely they're able to follow these dosing schedules and how well they get their drug on time with their insurance. There are just so many factors that play into real life care that are controlled for in clinical trials.

Rebecca Mashaw:

The Bath Ankylosing Spondylitis Disease Activity Index scores indicated poor disease control among all patients, you noted in your article. Were you able to determine why this was the case? Again, was it patient adherence? Was it medication choice, dosing? Again, all of those factors that we've already discussed? Comorbidities? Are all of these contributing to this poor control?

Dr. Jessica Walsh:

Yes, another fantastic question. The disease activity with the patients in this population was higher than what has been reported in other studies. So observational studies, as well as some of those clinical controlled trials that we just talked about. And we don't know exactly why. Some of it is probably just that there's a lot of poorly controlled disease out in the community that is getting captured by the survey. There may also be some selection issues, meaning that people who are doing fantastically well may be less likely to look for and sign up for a survey or a support group or other processes for better understanding their disease. So that's a really hard thing to assess, but it's possible that we are capturing information for the subset of the overall population who's doing a little bit less well with their disease control.