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Introduction: Chronic idiopathic constipation (CIC) is a prevalent functional gastrointestinal disorder diagnosed based on patient-reported symptoms and the absence of structural gastrointestinal abnormalities. Individuals with CIC typically institute dietary changes and use stool softeners or over-the-counter (OTC) laxatives, possibly at the direction of a healthcare provider, before prescription medications for CIC are initiated. Although highly prevalent, there is limited information regarding CIC patient experiences with OTC medications. Methods: This post-hoc analysis used patient-reported data from a questionnaire administered during patient screening for a prospective linaclotide Phase 3b clinical trial in patients with CIC (N = 1482 screened). The questionnaire asked patients to report their experiences with OTC CIC medications over the preceding 6 months. Results: Among patients with screening responses (N = 1423), most were female (85%) and white (66%), with a mean age of 48.9 years. A high proportion of patients had used one or more OTC medications (70% had ≥1 OTC; 19% had ≥3 OTCs), with the majority being bisacodyl (33%) and polyethylene glycol (30%). The most commonly cited reason for stopping an OTC medication was insufficient symptom relief (17–40%). The majority of patients taking OTC medications reported no or little satisfaction with the medication's effect on their constipation (62%) and CIC-specific abdominal symptoms (78%). Many patients had little to no confidence in bowel movement (BM) frequency after taking OTC medications and their confidence in their ability to predict BM timing was also low (49–81% not at all confident). Conclusions: Treatment effects on individual CIC symptoms, predictability of bowel habits, and satisfaction with treatment are all important factors for healthcare providers and patients to consider when establishing an effective treatment regimen for CIC. Trial registration number: NCT01642914 [ABSTRACT FROM AUTHOR]

Introduction: Linaclotide improves abdominal pain and constipation in patients with constipation-predominant irritable bowel syndrome (IBS-C). Patients report additional bothersome abdominal symptoms of bloating and discomfort. The intention of this study was to evaluate linaclotide's efficacy in relieving IBS-C-related abdominal symptoms (bloating, discomfort, and pain) using a novel multi-item Abdominal Score (AS)., Methods: Patients with IBS-C with abdominal pain ≥3 (0-10 scale) were randomized to linaclotide 290 μg or placebo daily for 12 weeks. The AS, derived from the Diary for IBS Symptoms-Constipation, is the average of abdominal bloating, discomfort, and pain at their worst (0 = none, 10 = worst possible). The primary end point was overall change from baseline (CFB) in AS. Secondary end points included CFB in 12-week AS evaluated using cumulative distribution function and 6-week/12-week AS responder (AS improvement ≥2 points for ≥6-week/12-week)., Results: Overall, 614 patients (mean age 46.7 years; 81% female) were randomized. All prespecified end points showed significant benefit of linaclotide vs placebo. The mean overall CFB AS reduction for linaclotide was -1.9 vs -1.2 for placebo (P < 0.0001); the 6-week/12-week AS responder rate was 40.5% for linaclotide vs 23.4% for placebo (odds ratio = 2.2 [95% confidence interval, 1.55-3.12; P < 0.0001]). Diarrhea was the most common treatment-emergent adverse event (linaclotide = 4.6%, placebo = 1.6%)., Discussion: Linaclotide significantly reduced multiple abdominal symptoms important to patients with IBS-C (bloating, discomfort, and pain) compared with placebo, as measured by a novel multi-item AS. The AS, derived from the Diary for IBS Symptoms-Constipation, should be considered for use in future IBS-C clinical studies to measure clinically meaningful improvements beyond traditional end points., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

BACKGROUND: Irritable bowel syndrome with diarrhea (IBS-D) is a chronic disorder of gut-brain interaction that negatively affects work productivity and health-related quality of life (HRQOL). IBS-D therapeutic options are limited and include loperamide, an over-the-counter μ-opioid receptor agonist commonly used as an antidiarrheal agent, and eluxadoline, a mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist approved in the United States for the treatment of IBS-D in adults. OBJECTIVE: To characterize the effect of eluxadoline on work productivity and HRQOL in patients with IBS-D with previous inadequate response to loperamide. METHODS: The Work Productivity and Activity Impairment Questionnaire for IBS-D (WPAI:IBS-D), Centers for Disease Control and Prevention Healthy Days Core Module (CDC HRQOL-4), and EuroQoL-5 Dimension (EQ-5D) instruments were administered at baseline and week 12 of a phase 4 clinical trial (RELIEF), assessing the efficacy and safety of eluxadoline treatment in adults with IBS-D reporting previous inadequate response to loperamide. Changes from baseline to week 12 for each assessment were evaluated using an analysis of covariance model. Indirect costs were calculated by converting overall work productivity losses into monetary values. RESULTS: A total of 346 patients were randomized to either eluxadoline (n = 172) or placebo (n = 174). From baseline to week 12, compared with placebo, twice-daily treatment with eluxadoline resulted in significantly greater reductions in absenteeism (2.6%; P = 0.046). Numerically greater decreases in presenteeism, overall work productivity loss, and daily activity impairment were also observed in patients receiving eluxadoline compared with those receiving placebo ( P = not significant for each). Numerical reductions in overall work productivity loss from baseline to week 12 translate to approximately 2.4 hours per patient per week (123 hours annually) and correspond to an avoided overall work loss of $4,503 annually for an employee with IBS-D treated with eluxadoline. In addition, from baseline to week 12, treatment with eluxadoline led to a significantly greater reduction in the number of unhealthy days experienced (-1.7 days; P = 0.042), as well as numerical improvements in EQ-5D measures in comparison with placebo ( P = not significant for each). CONCLUSIONS: In patients with IBS-D reporting inadequate response to loperamide, eluxadoline treatment was associated with significant reductions in absenteeism and the number of unhealthy days experienced. Eluxadoline treatment of IBS-D may lead to significant cost savings via mitigation of losses in work productivity. DISCLOSURES: This study was sponsored by Allergan plc (before acquisition by AbbVie, Inc.). Allergan plc and/or AbbVie, Inc., was involved in the study design, collection, analysis, interpretation of the data, writing of the report, and the decision to submit the report for publication. Abel and Burslem are employees of AbbVie, Inc., and own stock/stock options. Brenner has served as a consultant, speaker, and/or advisor for Allergan plc (before acquisition by AbbVie, Inc.), Alnylam, Alpha Sigma, Arena, Bayer, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Shire, Synergy, and Takeda Pharmaceuticals. He is also supported in research by an unrestricted gift from the Irene D. Pritzker Foundation. Sayuk has served as a consultant and speaker for Allergan plc (before acquisition by AbbVie, Inc.), Gi Health Foundation, Ironwood Pharmaceuticals, Salix Pharmaceuticals, and Synergy. Portions of the current work were presented at AMCP Nexus; October 22-25, 2018; Orlando, FL.

As expected, pharmacy costs increased with the introduction of this new treatment in a market dominated by over-the-counter and generic treatments. On the other hand, outpatient GI-related and irritable bowel disease health care resource use and costs substantially decreased among commercial and Medicare patients following linaclotide treatment initiation.