Pediatric IBS-C and Functional Constipation in Managed Care

Welcome to Unscripted, the AMCP podcast, a look inside managed care pharmacy.

Jessica: IBS-C and functional constipation are commonly encountered and difficult to treat conditions. Linzess had a recent label expansion to include these disease states. This new pediatric indication is more than a label change. It represents an opportunity for earlier intervention in children with chronic functional bowel disorders that can affect daily functioning, school attendance, family wellbeing, and quality of life.

In this episode, we'll explore the evidence behind these approvals and what they mean for patients, providers, and managed care. This episode of Unscripted, the AMCP podcast, is sponsored by AbbVie Inc. They find answers that make life better for patients and our world. I'm Jessica Fann, Program Director for Research and Strategic Partnerships at Vanderbilt Specialty Pharmacy and your guest host for today's podcast.

Joining us today will be Dr. Jason Dranove. Dr. Dranove is board-certified in general pediatrics and pediatric gastroenterology with almost 20 years of experience. He currently serves as the Medical Director of Gastroenterology and Motility Program at Atrium Health Levine Children's Hospital and is an Associate Professor of Pediatrics at Wake Forest University School of Medicine.

Thanks for being here today, Dr. Dranove. 

Dr. Dranove: Jessica, thank you very much. It's very nice to be here, and thank you for the invitation. 

Jessica: To help frame our discussion, can you help listeners understand the key differences between pediatric IBS-C and functional constipation? 

Dr. Dranove: Sure. So there are a lot of similarities, but by definition, irritable bowel with constipation, there's going to be a pain component along with constipation, and the pain component tends to be at least as or a little bit more prominent than the constipation component.

Whereas, with functional constipation, the diagnostic criteria really focuses more around the constipation itself the frequency of bowel movements, the form of the bowel movements, fecal soiling. So you can have pain with constipation, with functional constipation, so sometimes there's a little bit of a judgment call in the terminology, but essentially, I think the pain is the main differentiator.

Jessica: Thanks for describing those, Dr. Dranove. Why is it important to discuss pediatric IBS-C and functional constipation together rather than as separate disease states? 

Dr. Dranove: It's important because they often sort of coexist and can even be hard to differentiate just on diagnostic criteria. So when the primary problem and the primary complaint is more based upon constipation, very infrequent bowel movements, fecal incontinence, straining- But there's not a major component of pain that is causing quality-of-life impairment.

You're going to probably go a little bit more down the functional constipation pathway. And if the problem is more pain-based with a lot of abdominal pain, but also there's a component of constipation, and maybe things get worse around the time you have to have a bowel movement, and then maybe it improves after the bowel movement, but you're not getting fecal impactions or just very severe constipation.

So it's important to kind of differentiate to some degree because it will, at some point, change the the management approach that you have. Because the treatments that may be a little bit more effective for functional constipation may not really help the pain component of irritable bowel.

And, interestingly, some research studies even have a hard time differentiating between functional constipation and irritable bowel constipation because they can be very similar. 

Jessica: How do these conditions affect a child's day-to-day life beyond GI symptoms? What impact do these disorders have on families and caregivers?

Dr. Dranove: That's a very important question. And as in any kind of chronic pediatric condition or disease it doesn't just affect the child. It has a major effect on the family, whether that be parents, siblings, and even grandparents are often helping take care of children as well. And, you know, there's very good data that shows that specifically constipation and fecal incontinence and irritable bowel do have negative impacts on quality of life.

They lead to increased loss of school, increased loss of work, certainly increased healthcare costs and utilization. But, you know, what really can't be accounted for is kind of the social disturbances that it can cause for children and their families when the center of their life becomes their child's constipation or debilitating abdominal pain.

Jessica: Right. Great. Well, thank you for explaining that. What does the current treatment journey typically look like for pediatric patients with IBS-C and/or functional constipation? 

Dr. Dranove: So for functional constipation, that, that's probably a little bit more common. Or it's actually probably a, a good bit more common, probably at least twice as common.

And, you know, there are evidence-based guidelines that exist from the North American Society of Pediatric GI, the European Society of Pediatric GI, and they kind of recently worked together on a guideline. Also, the North American Society works with the AGA, the American Gastro Association.

And these are all guidelines that have been put out within the last couple years. Essentially, the treatment for functional constipation is kind of three methods. There's going to be, You've got to get somebody disimpacted first. If they are completely full of stool, they have a big ball of poop stuck in there, or there's just poop all throughout their colon, you gotta get them disimpacted.

That may take a clean-out. We have various different protocols for doing that at home, rarely. But sometimes people do need to be hospitalized to get cleaned out. And then you've got your maintenance phase of treatment. So after you get disimpacted, you have to go on some kind of maintenance treatment, because if you don't, you're just going to get re-impacted and re-constipated again.

And, you know, the, sort of the first line recommendations are going to be osmotic laxatives, i.e., polyethylene glycol or magnesium-based salts. And then, also very importantly and underutilized in clinical practice and heavily emphasized in recent guidelines would be stimulant laxatives, which actually sort of trigger big contraction waves in the colon.

And those are going to be your senna-based products and bisacodyl. So if we're talking over-the-counter, we're talking Senokot or Ex-Lax, for the sennosides or senna products. And then Dulcolax is sort of the brand name for it, but bisacodyl is the drug. So those are kind of like your major functional constipation treatments.

We try not to use enemas or suppositories unless they're really necessary, and we don't want those to be a maintenance treatment. It would be a pretty, you know, those unique or a minority of cases where that's going to be part of regular treatment. 

Irritable with constipation, you know, interestingly it can be very difficult to treat because the constipation may not be that severe, but the abdominal pain may be the trickiest part. So treating the constipation to make sure that they're having regular soft bowel movements, which can, kind of be the same approach where you're using your osmotic or stimulant laxatives.

But the issue with IBS with constipation is, you know, data shows that you may help the constipation component of the irritable bowel, but your, you may not help the pain. So MiraLAX softens your poop and may get you stooling more regularly, but it, there are studies that show it doesn't affect pain. And then if you give stimulant laxatives, they may, again, work to help the constipation component and get you stooling more frequently, but it may actually cause more cramping, and if you have sensitive nerves, that could actually make your IBS symptoms worse.

So I'm, it's probably a decent segue into where you're headed with the conversation. So we do need something more for IBS constipation. And even functional constipation, there's a certain percentage of patients who do not respond to your typical first-line treatments.

Jessica: I think you alluded to this already, but what symptoms tend to remain inadequately controlled despite standard management strategies? 

Dr. Dranove: I would say, for, on the functional constipation side, I would say fecal incontinence. You can get somebody stooling more regularly. You can get their stool soft, but they still, for a variety of reasons, which would probably be, you know, I could talk for hours about that.

So a little outside the scope, but I would say incontinence would be the big one. And, you know, again, and that kind of bleeds into social isolation, depression, anxiety, you know, nutritional deficiencies. And then, you know, on the IBS with constipation side, it's really the, I would say the pain that goes along with, by definition, having irritable bowel, so the pain and then, you know, patients rarely only have one functional GI disorder.

I think adults are more common to come in kind of an easy diagnosis slam dunk, this is irritable bowel with constipation. But pediatric patients also have functional nausea, functional dyspepsia, functional bloating. I mean, there's a handbook called the Rome Criteria, and we're now up to version five, and it's hundreds of pages of sort of, you know, groupings of symptoms which fall under a specific diagnosis that don't have an obvious organic etiology.

And, you know, functional GI disorders probably cause more quality of life, as much quality of life impairment, as some of our chronic, more identifiable diseases, whether that be celiac disease, even some forms of mild inflammatory bowel disease. There's a better quality of life than, you know, poorly treated irritable bowel with constipation.

Jessica: Well, we've had an exciting new update. Linzess recently received expanded pediatric indication. Can you tell our viewers a little bit more about that and what evidence supported it, its expansion? 

Dr. Dranove: Sure. So Linzess would be in the category of drugs called secretagogues. So we talked about our osmotic laxatives, our stimulant laxatives.

So now we have a new class of medicine, which is called secretagogues, and what that means is that the medication is actually an agonist for receptors on the lining of the entire gut, and the medication doesn't get absorbed into your body. But as it's going through your gut, it activates these guanylate cyclase C receptors.

And what that does is essentially that increases both intracellular and extracellular cyclic GMP. And on the intracellular side, that is going to activate CFTR receptors, which secrete chloride into the lumen of the gut. And so that is going to help lubricate your gut. Water's going to follow it, and then that usually will cause some, you know, decrease in transit time, i.e., speeding up the gut. 

So you're kind of getting a little bit of stimulant effect and you're getting some osmotic effect. And then, you know, what the extracellular cGMP does is it actually can help to decrease like visceral hypersensitivity in pain sensory nerves in the gut. So that is kind of why it is helpful in the irritable bowel with the pain component.

So you're kind of getting multiple mechanisms. The initial studies on the pain were done in animal models. But there's basically studies for IBS-C in children aged seven to 17. And then you've got functional constipation, which is now approved. Initially, it was six to 17, and now it's actually been approved all the way down to age two years old, so two through 17.

And, you know, those are prospective studies, you know, that have well-defined metrics. The constipation studies focus mostly on bowel movement frequency and then the IBS-C which was a little bit of a smaller study. But they, you know, they looked at multiple metrics, but, you know, still the stool frequency's the major one.

But they do look at pain across both studies. And in the IBS study, you know, with the higher dosing of Linzess, specifically in the older kids you started to see some improvement in pain 

Jessica: Thanks for explaining how Linzess works and the important pathways. I know one thing that's at the top of most parents' minds is safety profile.

So could you characterize the overall safety profile observed across the pediatric studies? 

Dr. Dranove: Sure. So I have to reread the major studies within the last few days, and then also went to the FDA site and looked at their sort of drug profile. And, you know, I would say that what I'm reading in the studies really matches up very well to what, you know, we see in day-to-day clinical practice, where I would say in general, there's a very low risk of side effects in general.

There's a very low risk of any serious adverse events, and I did not pick up on any in the studies that could be correlated to the linaclotide itself. You know, the main side effect is going to be diarrhea. And in a sense, that's kind of what you're trying to create. You don't want to create diarrhea, but you're obviously trying to get the stool looser and move better.

But it's really, it's less than 10% of patients. And really abdominal pain is, you know, you see it occasionally in patients. But, you know, in the studies really there was no significant reports of abdominal pain. So, all in all, you know, these are side effects that are basically no different than, you know, your standard treatment.

And by the time you've kind of gotten through the first-line treatments, you know, the families generally are looking for, you know, something new. You know, they, they don't want to keep giving the same medications over and over. So if you feel like you've maximized the utility of the kind of the first-line drugs, obviously they are going to be concerned about side effects.

And, you know, fortunately, this drug is one that we can pretty confidently reassure them that we're not expecting anything major. And in fact, the biggest side effect or risk I kind of say is it may not work. It doesn't work for everybody. And, you know, no drug practically works for everybody.

And, you know, the research certainly shows that. So if you kind of frame that and, you know, we have various, you know, ways of kind of putting risk into perspective for parents to kind of make them feel comfortable. And we do use some medications we use in GI, particularly as a motility specialist where if you treat, you know, disorders of gut-brain interaction, we do use medications that do have real side effects.

So we have to know how to kind of risk stratify and explain this to parents so they can kind of make a decision about what they want to do. But this one's usually not a particularly difficult conversation. 

Jessica: That's great. Yeah, it's super exciting to have another option for these patients.

Now we're going to move on to the managed care aspect. How do pediatric functional GI disorders affect healthcare utilization and resource use? 

Dr. Dranove: I'm very glad you asked that. It affects resources on many different levels in variable degrees of severity. Just to give you a little perspective, we, in our office, we get so overwhelmed with requests for notes for medication administration at school for 504 plans which may vary from state to state, but those are a little bit more official plans that kids have if they're going to have to miss school or, you know, on a regular basis or may need to go to the nurse's office.

So, you know, again, there's very good data and very real experience with the fact that you're talking lost school, lost work for parents, significant usage of healthcare dollars and resources, ER visits, urgent care visits, doctor's visits, messaging through MyChart, which, you know, we just seem to need to keep hiring nurses and MAs to keep up with the volume of care that we need to give patients.

Procedures under anesthesia, hospitalizations. It can be a snowball effect and, you know, it can, I mean, in significant cases, functional GI disorders they can be disabling. They can lead to poor nutrition, and they're extremely difficult to treat.

You know, things where we have an exact biological mechanism and we know how to treat it, i.e., Crohn's disease, ulcerative colitis, celiac disease, H. pylori infection, et cetera, reflux, you know, those don't stress us out as much because you have a cause and you have clearly defined treatment options, based upon, you know, tangible evidence that you can show the parents, whether it be from labs or biopsies or radiographic studies.

But, you know, functional GI disorders are, they're somewhat invisible. All the testing is normal, kind of by definition. And in, in general, I would say all the testing is going to be normal. So you really have to learn how to talk to children and their parents and whoever else is caring for them to kind of validate that these concerns are real, they are experiencing these symptoms.

And at some point, you have to know when to stop doing testing and you really have to start delving into, to treating the symptoms based upon the most likely etiology. So not all irritable bowel is created equal. Some may be more triggered by certain foods. Some may be more triggered by stress or anxiety.

Some may be triggered by barometric pressure changes. You can't put these patients into like a, a strict algorithm, you know. You really have to kind of individualize it, get a history from each patient to see what's going to work for them. 

Jessica: Yeah. It seems like there's so many complexities and several aspects to take into account when you're caring for these patients.

So how might earlier symptom control affect downstream healthcare utilization and quality of life outcomes? 

Dr. Dranove: Yeah. So, you know, this is another area where there's clearly good evidence across various specialties, various conditions where earlier identification and intervention is going to lead to better treatment outcomes and decrease costs.

You know, one of the articles, you know, it was reviewing, stated that, and, you know, one large study showed that there's over two years on average between the time constipation symptoms start until the time patients are referred to a specialist, and that does not mean that every patient with constipation needs to see a specialist.

But the average age of onset of constipation is two, okay? And between age two to four being by far the highest age of onset. And, you know, a lot, sometimes it is more of a sort of stool withholding or kind of a willful issue, but many times it's not.

And, you know if you can get on top of treating that early and prevent chronic stool backup, which then can turn into soiling and then can turn into a stretched out colon, which then can actually cause colonic dysfunction and sensory dysfunction, it's going to be a lot easier to treat that if you get on top of it early.

Jessica: That makes sense. So much great insightful information provided today. Thank you, Dr. Dranove for being here. 

Dr. Dranove: Thank you very much for having me, and, I hope you guys enjoyed the podcast. 

Jessica: And thank you for listening to this episode of Unscripted, the AMCP podcast. This episode was sponsored by AbbVie Inc.

For more information about AbbVie, go to abbvie.com.