967 Plecanatide, Like Uroguanylin, Activates Guanylate Cyclase-C Signaling in a pH-Dependent Manner in T84 Cells, and in Murine Intestinal Epithelial Cells and Tissues (original) (raw)

Chronic constipation (CC) is a common multi-symptom disorder of heterogeneous pathogenesis. Opioid analgesics are known to be an important cause of constipation symptoms. Recently, multiple drugs have gained regulatory approval for the treatment of opiate-induced constipation. Despite this, little is known about the clinical characteristics of constipated patients who are taking opioids. We utilized a novel electronic platform to conduct a national US survey to better understand the clinical profiles of constipated patients taking and not taking opioids. Methods: A national US survey was conducted using a digital adaptation of the NIH PROMIS® questionnaires called My GI Health. US adults (‡18 years) were invited to complete the survey utilizing an incentivized, opt in list provided by a contract research company (Cint®). Participants provided demographic information, severity & frequency data for the 8 most common GI symptoms (abdominal pain, heartburn, dysphagia, nausea, bloating, constipation, diarrhea, bowel incontinence), & use of OTC/prescription medications. Standard statistical methods were used to compare characteristics of respondants reporting constipation who were taking opioids (opiate associated constipation=OAC) or not taking opioids (non-opioid constipation=NOC). Regression models adjusted for age, sex, race/ethnicity, education, marital status, employment status, and household income. NOC subjects served as the reference group. Results: 71,813 adults completed the survey. 13,343 subjects reported constipation symptoms within 7 days of completing the survey. Of those with constipation, 1671 were actively using opiates (12.5%) while 11,672 (87.5%) were not. Demographic information showed OAC subjects were older, more likely to be male, less likely to have a graduate degree and more likely to be unemployed than NOC subjects (p<0.001 for these items). Subjects with OAC had a greater burden of constipation symptoms than NOC (table 1). Further, subjects with OAC had a greater burden of all GI symptoms assessed. OAC patients were more likely to endorse all the other GI symptoms assessed except for diarrhea (table 2). Based upon PROMIS composite scores for all 7 remaining lower and upper GI symptoms (table 1), OAC patients had more frequent & severe GI symptoms than NOC subjects (all comparisons on linear regression model p<0.001). These results were confirmed in a smaller group of respondants who reported constipation for more than 4 weeks. Conclusions: This is the largest survey to characterize the clinical phenotypes of OAC and NOC. OAC patients had a greater burden of GI complaints attributable to the lower and upper GI tract. This may be the consequence of opioid effects throughout the GI tract and CNS and might have implications regarding treatment choice in OAC vs. NOC patients. Table 1: GI PROMIS symptom scores in NOC vs. OAC a GI PROMIS score for individual symptoms is on a 0-100 percentile scale. b Global GI PROMIS score is on a 0-800 scale.