Mo1262 Effects of Baseline Abdominal Pain on Response to Lubiprostone in Patients With Constipation-Predominant Irritable Bowel Syndrome

Abstract

Background: IBS-D is characterized by a diverse group of core symptoms that include abdominal pain, altered stool consistency, bloating, and urgency. To assess the ability of rifaximin (RFX) to produce a common response to these multiple symptoms, the study design incorporated an open-label (OL) enrichment phase where RFX responders were identified for potential inclusion in a repeat treatment phase. This analysis describes the profile of symptom improvement from the OL enrichment phase. Methods: Subjects with IBS-D (Rome III criteria) with average symptom severity scores of ≥ 3 for abdominal pain (AP, scale 0-10) and bloating (scale 0-6), with ≥ 2 stools with Bristol Stool Scale (BSS) Type 6 (loose) or 7 (watery) during the 7-day baseline were entered into the OL phase. In OL, all subjects received RFX 550 mg TID for 2 weeks, followed by a 4-week, treatment-free assessment period. A responder, as defined by the FDA composite endpoint, was required to achieve a ≥30% decrease from baseline in mean weekly AP score, and simultaneously respond for stool consistency (SC) with a ≥50% decrease from baseline in number of days/ week with BSS Type 6 or 7 stools, for ≥2 weeks of a 4-week period. In addition to the FDA composite endpoint, additional core symptoms of IBS-D were assessed, including bloating (6-point scale; 0=not at all, 6=a very great deal), urgency (Yes/No during the last 24 hours), and overall IBS symptoms (How bothersome were your symptoms of IBS in the last 24 hours?; 6-point scale; 0 = not at all, 6 = a very great deal). Results: A total 2579 subjects (mean age: 46.4; 68% female) received RFX treatment during the OL phase, of which 2331 were evaluable for efficacy. Based on the pre-specified FDA composite definition of response, which stipulates improvements in both AP and SC on the same weeks, 1074 (46%) subjects were deemed responders in the 4-week follow-up period. Another 14% of subjects responded only to the SC component, while a different 11% of subjects responded only to the AP component. Finally, 1% of subjects experienced improvements for AP and SC, but not on the same weeks of the 4-week assessment period. Collectively, 72% of evaluable subjects experienced improvement on at least one component of the FDA composite endpoint. When all symptoms were evaluated independently (AP, SC, urgency, bloating, and overall IBS symptoms), >50% of subjects were deemed to be responders following a 2-week course of OL RFX (Table). Conclusions: These findings suggest that over 70% of patients experience improvement in at least one of the two symptoms of the FDA composite endpoint. Improvements for bloating, urgency, and overall IBS symptoms, suggest that the benefit of rifaximin may extend beyond symptoms comprising the FDA composite endpoint. Proportion of Responders for IBS-D Symptoms During Open-label Phase