A post hoc analysis of three clinical trials of tenapanor (Ibsrela, Ardelyx) shows the drug works within weeks to improve bowel function and abdominal symptoms in people with irritable bowel syndrome with constipation (IBS-C).
“Although onset of action occurs within the first week, continued therapy allows for a greater percentage of patients to achieve a meaningful response,” wrote Brian Lacy, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, and co-authors in an abstract.
Dr. Lacy presented the results of this work at the annual scientific meeting of the American College of Gastroenterology (ACG) in Vancouver, Canada.
Tenapanor acts as an inhibitor of the sodium-hydrogen exchanger 3 (NHE3) and works to reduce dietary sodium absorption, which, in turn, leads to retention of fluid in the intestinal lumen, resulting in softer stool and accelerated intestinal transit, he explained.
Tenapanor is approved by the US Food and Drug Administration for adults with IBS-C.
The major goal of the analysis presented at ACG was to identify times to responses for individual symptoms, said Dr. Lacy in an email exchange with GI & Hepatology News.
Prior studies focused on global improvement in IBS-C symptoms using the FDA-approved definition of a responder: A patient who experienced at least a 30% reduction in the weekly average abdominal pain score and an increase of at least one complete spontaneous bowel movement (CSBM) in the same week for at least 6 of the first 12 treatment weeks.
“Thus, we thought it important to pool all of the data together for this post-hoc analysis, as clinicians and patients often wonder when an individual symptom will respond,” Dr. Lacy wrote in an email.
Dr. Lacy and colleagues conducted a post hoc analysis of pooled data from the phase 2b (NCT01923428) and phase 3 T3MPO-1 (NCT02621892) and T3MPO-2 (NCT02686138) studies to evaluate time to onset of tenapanor effect on bowel function and on individual and global abdominal symptoms in patients with IBS-C.
This resulted in a pooled population of 1372 intent-to-treat patients (688 placebo, 684 on the study drug), with demographics generally similar across the studies, they said.
They found that the median time to CSBM was 2 weeks, with an estimated response probability of 52.3% by week 2, 72.5% by week 8, and 76.7% by week 12.
The median time to abdominal pain response was 4 weeks; the estimated response probability was 54.6% by week 4, 67.9% by week 8, and 72.3% by week 12.
The median time to abdominal bloating response was 5 weeks; the estimated response probability was 48.1% by week 4, 61.9% by week 8, and 67.7% by week 12.
“The teaching message to patients and providers is not to give up too early; staying on this medication allowed 25% more people to improve symptoms,” Dr. Lacy wrote.
In separate interviews, two other researchers Anthony Lembo, MD, AGAF, director of research for Cleveland Clinic’s Digestive Disease & Surgery Institute, and Brooks D. Cash, MD, AGAF, chief for gastroenterology, hepatology, and nutrition at the University of Texas Health Science Center at Houston, agreed with Dr. Lacy’s message.
The study will help in counseling patients who may need to wait a bit to see a response from tenapanor, Dr. Lembo said.
“You wish patients would get better right away of course,” he said, but there can be some delay, even in cases where a drug will ultimately work for a patient.
Patients want to know if they should continue and if it is worth getting another prescription for another month if they haven’t had a significant improvement response, Dr. Lembo said.
Both Dr. Lembo and Dr. Cash said that it takes time for many drugs, not just these medications, to produce a noticeable effect for patients.
Still, “disorders of the gut-brain interaction likely do require a longer runway time to really assess their effects on multiple symptoms,” Dr. Cash said.
The tenapanor research presented at ACG will help in conveying that message to patients, Dr. Cash said.
“It also reinforces for clinicians not to be impatient,” he said.
Dr. Lacy and co-authors directed the development of the poster, and medical writing support was provided by Ashfield MedComms, an Inizio company, and funded by Ardelyx. Dr. Lacy has financial and consulting relationships with AbbVie, Ardelyx, Gernelli, Ironwood Pharmaceuticals, Salix, and Sanofi, Co-authors are employees of Ardelyx. Dr. Lembo and Dr. Cash have financial relationships with Ardelyx and other makers of IBS drugs.
This article originally appeared on MDedge.com, part of the Medscape Professional Network.
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