Kirk Thame, MD, associate professor, pediatric gastroenterology, hepatology, and nutrition, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee, explains how linaclotide differs from other treatment options for pediatric functional constipation, and why children will benefit from its recent FDA approval.
In this Contemporary Pediatrics® interview, Kirk Thame, MD, associate professor, pediatric gastroenterology, hepatology, and nutrition, Monroe Carell Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee, explains how linaclotide differs from other treatment options for pediatric functional constipation, and why children will benefit from its recent FDA approval.
Transcription (edited for clarity):
Hi and thank you so much for joining us. I'm Joshua Fitch, editor of Contemporary Pediatrics®.
Kirk Thame, MBBS:
I'm Dr. Kirk Thame, I'm an associate professor in pediatric gastroenterology, hepatology, and nutrition at Vanderbilt Children's.
Thank you so much for taking the time to speak with us. Today we're discussing the recently FDA-approved linaclotide. First Dr. Thame, can you just explain how can linaclotide change the treatment landscape for children, adolescents, and teens, age 6 to 17 years with functional constipation.
The biggest way will be that it gives us another to another option for treatment. It performs similarly to market laxatives will [which] pull water into the intestines, keeping the stool from getting too hard. Linaclotide and the secretagogues are similar, but instead of pulling water in, they basically push water into the intestines… So, the mechanism of action is similar. I think that one of the major differences is going to be that it comes in tablet form. So that market laxatives that we have, you know, MiraLAX, Milk of Magnesia... they're all liquid forms. Some of our patients have problems with taste, even though MiraLAX, for instance, is supposed to be tasteless, and odorless, some children can know when it's mixed in, or it makes it just a little bit thicker. All the issues that you have with your liquid medicine will go away for either children who can take tablets or in the study, it was actually opened and sprinkled on food or in liquids. So, it's going to be an easier way to take it for many children, and so that will be a game-changer in terms of an option for children [that find it] difficult to take other forms of laxatives.
Dr. Thame how often will linaclotide need to be taken for this patient population and how can that impact that ease of access you just mentioned?
Dosing will be once a day. So that should also improve compliance. It's always easy to take something that's just once a day rather than twice or three times a day.
In the clinical trials, what adverse events were associated with linaclotide? What can healthcare providers, what do they need to be aware of when giving this out, and what can the patients expect in that regard as well?
The largest concern for linaclotide and the secretagogues have always been just severe diarrhea [In children aged 6 to 17 years, severe diarrhea was reported in <1% of 72 mcg linaclotide-treated patients1]. It carries a black box warning ["Risk of serious dehydration in pediatric patients less than 2 years of age"] because the intestinal mice in studies, some of them actually died from dehydration. And so that has put a limit on the age group that we are allowed to prescribe for. Having gone through the study, the study proves that it's safe and allows us to use a medication. I would just go back to the actual logic of the mice were baby mice in the studies. A child who is verbal, who can talk, meaning the children who in the age group of the study, can tell if they're thirsty. Most of them will be able to walk to the fridge if they are actually thirsty. So severe diarrhea is a possibility, serious injury from it should be very unlikely.
[Linaclotide black box language]:
Dr. Thame is there anything else you'd like to add on this recent FDA approval of linaclotide and how it can further treat this patient population?
Honestly, I'm looking forward to being able to use it. Right now, a few insurance companies will cover it. Many times, it will take a lot of legwork to actually get it covered, if at all. I welcome having yet another drug that we can use because every child is different, the taste is different, the tolerability to medications are different, and so it will be very helpful. You know, if you look at the studies, if you follow children with constipation, only about half of them are actually off medication 6 to 12 months after they've started for constipation. So, it seems like a simple disease, it seems like it's a very, easy problem to get over, but actually it turns out to be a long-term problem and a lot of that is due to compliance as well. If you can improve compliance, you can put improve outcomes. Linaclotide will give us one more chance to achieve that.
1. Ironwood pharmaceuticals announces FDA approval of new indication for LINZESS (linaclotide) for the treatment of functional constipation in pediatric patients ages 6-17 years-old. June 12, 2023. Accessed June 16, 2023. https://investor.ironwoodpharma.com/press-releases/press-release-details/2023/Ironwood-Pharmaceuticals-Announces-FDA-Approval-of-New-Indication-for-LINZESS-linaclotide-for-the-Treatment-of-Functional-Constipation-in-Pediatric-Patients-Ages-6-17-Years-Old/default.aspx