Presenting Author: ANTHONYT. LEMBO Additional Authors: GILESR. LOCKE, WILLIAMD. CHEY, CAROLINEB. KURTZ, ROBYNT. CARSON, MOLLIEJ. BAIRD, MARKG. CURRIE, JEFFREYM. JOHNSTON Corresponding Author: ANTHONYT. LEMBO Affiliations: Beth Israel Deaconess Medical Center; Department of Gastroenterology and Hepatology, Mayo Clinic; Department of Internal Medicine, University of Michigan; Ironwood Pharmaceuticals, Inc.; Forest Research Institute Objective: To examine the effects of linaclotide, a guanylate cyclase-C agonist, on response to patient-ratings-of-change (PRC) questions and extent of improvement in individual IBS-C symptoms within PRC categories. Methods: In two Phase 3 IBS-C trials of linaclotide,
patients rated abdominal symptoms (pain, bloating, fullness, cramping, discomfort) and bowel symptoms (spontaneous bowel movement [SBM] and complete SBM [CSBM] frequency, straining, stool consistency, unsuccessful BM attempts) daily. PRCs XL765 nmr Selinexor nmr at Treatment
Period weeks 2, 4, 8, and 12 included relief/improvement for each specific abdominal/bowel symptom for the prior 7 days, compared to before the trial began, using a 7-point balanced ordinal scale (1 = completely improved/relieved, 4 = unchanged, 7 = as bad as I can imagine). Overall Degree of Relief of IBS symptoms was assessed weekly using the same scale. P-values were obtained from Cochran-Mantel-Haenszel tests comparing linaclotide to placebo. Results: For all PRC parameters, significantly more linaclotide vs placebo patients were completely/considerably relieved FER (Table 1); more
placebo than linaclotide patients were unchanged, somewhat worse, or considerably worse/as bad as I can imagine. Although patients on linaclotide generally reported greater improvement in symptoms across all categories of relief/improvement, patients with greater relief/improvement ratings tended to report greater changes in corresponding symptom scores, regardless of treatment group (Table 2). Conclusion: Linaclotide was approximately twice as likely as placebo to provide complete/considerable relief of IBS symptoms overall (46% vs 23%) as well as individual symptoms. These results provide perspective on magnitude of change that corresponds to patient reporting of complete/considerable relief of individual and overall IBS-C symptoms. Key Word(s): 1. IBS-C; 2. linaclotide; 3. ratings of change; Table 1. Patient-Reported Rating of Change (Week 12), Percentage of Patients in Each Category by Treatment Group Completely/Considerably Relieved Somewhat Relieved Unchanged Somewhat Worse Considerably Worse/As Bad As I Can Imagine PBO LIN PBO LIN PBO LIN PBO LIN PBO LIN ITT population. Table 2. Mean Change in Symptoms Scores for Each PRCQ Category Completely/Considerably Relieved Somewhat Relieved Unchanged Somewhat Worse Considerably Worse/As Bod As I Can Imagine PBO LIN PBO LIN PBO LIN PBO LIN PBO LIN ITT population.