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Kenny Walter is an editor with HCPLive. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with R&D Magazine. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.
In a study presented at ACG, investigators focus on quality of life improvements for patients with irritable bowel syndrome.
New data presented during the 2021 American College of Gastroenterology meeting shows plecanatide is a beneficial treatment in improving the quality of life for patients with irritable bowel syndrome with constipation (IBS-C).
In an interview with HCPLive®, Darren M Brenner, MD, Associate Professor of Medicine (Gastroenterology and Hepatology) and Surgery, Northwestern University Feinberg School of Medicine, explained the importance of the results and why quality of life should be a target for clinical trial endpoints.
HCPLive: Can you explain the study you presented at ACG 2021 on plecanatide?
Brenner: So the purpose of this study was to determine how plecanatide impacted health related quality of life. We have a lot of different validated survey tools that we can use to define that. And historically, we've looked at the differences in these quality of life parameters over time.
But these tools have also been validated for what we call a clinically meaningful difference. I think that that's a most more robust way to look at assessing this issue because instead of looking at raw numbers for specific types of symptoms, it gives you an overall idea of how well these medications are impacting patients and patient populations.
And so this was a retrospective post hoc analysis of the two, phase three clinical trials for chronic idiopathic constipation, and the two phase three trials for irritable bowel syndrome with constipation, that were used for regulatory purposes to get this drug approved for those indications.
So what we did is we took those populations, and we have the data from two scales. One's called the Patient Assessment of Constipation Quality of Life Questionnaire, which contains about 28 items. And the other one is the Irritable Bowel Syndrome Quality of Life Questionnaire, which contains 34 items.
And these items are rated on particular scales, and we can gauge whether or not people are improving based on these questions and these scales over time.
We're trying to say overall clinically, how does this drug impact patients and what percentage of individuals can be considered overall responders.
HCPLive: In gastro and in particular IBS, how important is it for studies to focus on quality of life as a metric when testing new or existing drugs?
Brenner: I think it's very important because it gives you an overall assessment of what this does to a patient on a day to day basis, not in terms of symptoms, per se, but in terms of how they function.
This takes into account whether or not people are able to leave their house, go to social situations, feel comfortable in social situations when they're when they're worried being outside of their houses, whether they avoid food, how it impacts them sexually in their relationships.
So really kind of tangible, meaningful issues from a patient perspective.
Looking at these therapeutics, especially in the IBS-C space, there really aren't a lot of differences in terms of the outcomes for patients.
Looking at specific symptoms like frequency of bowel movements, or texture of stool or complete spontaneous bowel movements, the treatments really come out with similar differences compared to placebo.
Thus, it's very hard to gauge which therapeutics may be more effective just based on that raw data alone. So looking at quality of life gives practitioners and patients another meaningful way to look at how these therapeutics may be effective, but more importantly, maybe able to separate one from the others.
HCPLive: Now where are there still gaps in treating CIC and IBS-C?
Brenner: Well, I think that a lot of it comes down to differentiating our prognosticating, who's going to respond to one therapeutic over the other.
From my standpoint, that's kind of the holy grail because we have multiple different therapeutics for treating chronic constipation, irritable bowel syndrome, and constipation, we really have to start to identify who's going to respond to a particular drug versus another drug so that we're not just going through a litany of trial and error.
We're not there yet.
And again, that's why studies like this are important because we can look away from specifically symptom based profiles to quality based responses and see if those differences are present.
We also have to be better to find the underlying causes of the disorders. Once we're better at identifying those, we'll be able to formulate more targeted therapies.
HCPLive: What’s next for this drug? What still needs to be studied?
Brenner: So we've looked at, obviously, the efficacy of the therapeutic, that's been proven. We've looked at the quality of life and these studies show that these medications significantly improved quality of life compared to placebo.
In this study, we also tried to correlate these changes in quality of life to the associated symptoms, abdominal symptoms and bowel symptoms. There were weak correlations to both indicating that the overall general profile symptoms experienced by patients with chronic constipation and irritable bowel syndrome with constipation play a role in the impact of health related quality of life.
It's not just the abdominal symptoms or bowel symptoms that are going to impact that process. I think we need to get a better understanding these correlations, see how they really do affect patients day to day, day to day ability to function.
And that'll give us a better sense of when the how and when and how to use them.
HCPLive: How important is it to listen to patients when looking at quality of life because this is something they can easily convey?
Brenner: Yeah, this is extremely important. I mean, when patients come in, they tell us, this is how it's impacted my quality of life. And this has reduced my quality of life. And this is having a major impact on my quality of life.
That’s how they define it.
Remember that we do these clinical trials for chronic constipation, irritable bowel syndrome of constipation. The primary endpoints that get these drugs approved are established based on FDA protocols.
And the current protocols for IBS include reductions in abdominal pain, Crohn's, a 30% threshold and an increase of one complete spontaneous bowel movement a week for chronic constipation.
It's the number of complete spontaneous bowel movements a week maintained over X number of weeks, including the last part of the trial. That's not we ask patients when they come into our clinical practice.
I ask my patients, how are you doing, and they will talk in terms of frequency or texture or straining or incomplete evacuation. We'll also talk in terms of, I'll go to a restaurant now, I'll go to the movies, I don't have to be uncomfortable trying to get downtown in Chicago traffic. I'm not afraid to get on a plane. And that's really where we want to see these impacts that's most important to the patients.
In many instances, we may not completely cure their chronic constipation or irritable bowel syndrome with constipation, but they'll come in and say I'm comfortable where I am now on this medication because my quality of life has improved X percent or in these particular ways.
HCPLive: Is there any subgroup of patients in which you would not prescribe plecanatide to?
Brenner: You can’t use in children under the age of 6, it is contraindicated. it's also contraindicated under 18. We just don't have data on those populations.
There's data in the elderly showing that could be effective and across the spectrum of adults, ages 18-65. We're not aware that there any deficiencies in either sex or any ethnic backgrounds. It’s a very safe therapeutic.
It's a pH dependent analog of a chemical called uroguanylin, that’s secreted from the small intestine every time people eat.
So from that perspective, being analog of that human peptide, it makes it a very, very safe medication use across the spectrum.