Harris, Lucinda A.

Ehlers-Danlos syndrome (EDS) is a heritable collagen disorder characterized by joint hypermobility and tissue fragility, with hypermobile Ehlers-Danlos syndrome (hEDS) as the most common subtype. Rates of gastroesophageal reflux disease (GERD) symptoms are reportedly higher in the hEDS population than the general population. This could be caused by increased esophageal hypersensitivity and/or connective tissue laxity leading to hiatal hernias or increased relaxations of the lower esophageal sphincter. Despite this, Barrett’s esophagus rates in hEDS do not appear to be higher than in the general population. This review examines the epidemiology, pathophysiology, and unique considerations for management of GERD in hEDS.

Patients receiving opioid analgesics may experience constipation [ie, opioid-induced constipation (OIC)], require treatment to induce laxation, and may be at risk for gastrointestinal perforation, an uncommon but potentially life-threatening condition. Management of OIC includes treatment with over-the-counter laxatives and peripherally acting μ-opioid receptor antagonists (PAMORAs; methylnaltrexone, naloxegol, naldemedine). In patients receiving treatment for OIC, gastrointestinal perforation may result from the laxation process, causing disruption of the gastrointestinal lining that may already have compromised integrity. A PubMed literature review and a search of the US Food and Drug Administration Adverse Event Reporting System database identified several cases of gastrointestinal perforation (life-threatening or with mortality) across the range of agents administered for the treatment of OIC or other constipation types. Methylnaltrexone in the subcutaneous form was the first PAMORA approved for OIC. Its real-world use in the ∼6 years before the availability of another OIC-indicated PAMORA helped establish the adverse-event profile of the class, and experience has been gained in identifying and treating appropriate patient populations. Class labeling of PAMORAs includes a contraindication in patients with known or suspected gastrointestinal obstruction or increased risk of recurrent obstruction. Appropriate patient selection during laxation therapy for OIC, regardless of treatment plan, involves consideration of the overall risk versus benefit in patients at increased risk of perforation due to comorbid medical conditions, concurrent medications, or recent gastrointestinal procedures. After initiating treatment for OIC, clinicians should assess the effectiveness of laxation therapy and carefully monitor for signs of gastrointestinal perforation.

INTRODUCTION: This post hoc analysis evaluated the efficacy of tenapanor on abdominal symptoms in patients with irritable bowel syndrome with constipation. Abdominal symptoms assessed included pain, discomfort, bloating, cramping, and fullness. METHODS: The abdominal symptom data were pooled from 3 randomized controlled trials (NCT01923428, T3MPO-1 [NCT02621892], and T3MPO-2 [NCT02686138]). Weekly scores were calculated for each abdominal symptom, and the Abdominal Score (AS) was derived as the average of weekly scores for abdominal pain, discomfort, and bloating. The overall change from baseline during the 12 weeks was assessed for each symptom weekly score and the AS. The AS 6/12-week and 9/12-week response rates (AS improvement of ≥2 points for ≥6/12- or ≥9/12-week) were also evaluated. The association of weekly AS response status (reduction of ≥30%) with weekly complete spontaneous bowel movement (CSBM) status (=0 and >0) was assessed. RESULTS: Among 1,372 patients (684 tenapanor [50 mg twice a day] and 688 placebo), the least squares mean change from baseline in AS was −2.66 for tenapanor vs −2.09 for placebo ( P < 0.0001). The 6/12-week AS response rate was 44.4% for tenapanor vs 32.4% for placebo ( P < 0.0001), and for 9/12-week AS, 30.6% for tenapanor vs 20.5% for placebo ( P < 0.0001). A significant association between weekly CSBM status and weekly AS response status was observed each week ( P < 0.0001), with a greater proportion achieving an AS reduction in patients with >0 CSBMs in a week. DISCUSSION: Tenapanor significantly reduced abdominal symptoms in patients with irritable bowel syndrome with constipation, particularly pain, discomfort, and bloating measured by AS, compared with placebo.

INTRODUCTION: Chronic idiopathic constipation (CIC) is a common disorder associated with significant impairment in quality of life. This clinical practice guideline, jointly developed by the American Gastroenterological Association and the American College of Gastroenterology, aims to inform clinicians and patients by providing evidence-based practice recommendations for the pharmacological treatment of CIC in adults. METHODS: The American Gastroenterological Association and the American College of Gastroenterology formed a multidisciplinary guideline panel that conducted systematic reviews of the following agents: fiber, osmotic laxatives (polyethylene glycol, magnesium oxide, lactulose), stimulant laxatives (bisacodyl, sodium picosulfate, senna), secretagogues (lubiprostone, linaclotide, plecanatide), and serotonin type 4 agonist (prucalopride). The panel prioritized clinical questions and outcomes and used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence for each intervention. The Evidence to Decision framework was used to develop clinical recommendations based on the balance between the desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS: The panel agreed on 10 recommendations for the pharmacological management of CIC in adults. Based on available evidence, the panel made strong recommendations for the use of polyethylene glycol, sodium picosulfate, linaclotide, plecanatide, and prucalopride for CIC in adults. Conditional recommendations were made for the use of fiber, lactulose, senna, magnesium oxide, and lubiprostone. DISCUSSION: This document provides a comprehensive outline of the various over-the-counter and prescription pharmacological agents available for the treatment of CIC. The guidelines are meant to provide a framework for approaching the management of CIC; clinical providers should engage in shared decision making based on patient preferences as well as medication cost and availability. Limitations and gaps in the evidence are highlighted to help guide future research opportunities and enhance the care of patients with chronic constipation.