Tu1068 Effects of Linaclotide Treatment on Patient-Reported Ratings of Change for Symptoms of Irritable Bowel Syndrome With Constipation (IBS-C): Pooled 12-Week Findings From Two Phase 3 Trials

Abstract

Introduction: Linaclotide, an investigational drug, is a minimally-absorbed guanylate cyclaseC receptor agonist that has demonstrated symptom improvement in IBS-C patients in two large Phase 3 trials. Patient-reported ratings of change for individual and overall IBS-C symptoms provide interpretation of clinical relevance for patient-reported outcome measures of abdominal and bowel symptoms. Aim: To examine the effects of linaclotide on patientreported ratings of change and the extent of improvement in individual IBS-C symptoms within these patient-reported ratings of change categories. Methods: In two Phase 3 IBS-C trials of linaclotide, patients reported daily ratings for 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) via an interactive voice response system diary (pooled data). Patient-reported ratings of change included relief or improvement for each specific abdominal and bowel symptom, respectively, for the prior 7 days, at study visits during weeks 2, 4, 8, and 12 of the Treatment Period, 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 also assessed weekly using the same 7-point balanced scale. P-values were obtained from the Cochran-Mantel-Haenszel (CMH) row-mean score tests comparing linaclotide to placebo. Results: For all of the patient-reported rating-of-change parameters, significantly more linaclotide vs placebo patients were completely/considerably relieved (Table 1); additionally, more placebo than linaclotide patients reported their symptoms as unchanged, somewhat worse or considerably worse/as bad as I can imagine. Although patients on linaclotide, in general, reported greater improvement in symptoms across all categories of relief/improvement, patients who had greater relief/improvement ratings tended to report greater changes in symptom score for the corresponding symptom, regardless of treatment group assignment (Table 2). Within the category of completely/considerably relieved, patients on linaclotide tended to report greater benefit than those patients on placebo. Conclusions: In clinical studies, linaclotide was approximately twice as likely as placebo to provide complete or considerable relief for overall and individual abdominal and bowel symptoms in IBS-C patients. Nearly half of IBS-C patients randomized to linaclotide reported complete/considerable relief of their IBS symptoms. This analysis provides perspective on themagnitude of change in patients' individual symptoms that corresponds to reporting of complete/considerable relief of their individual and overall IBS-C symptoms. Table 1. Patient-Reported Rating of Change (Week 12), Percentage of Patients in Each Category by Treatment Group