Two Years on Linaclotide: Tolerability and Treatment Satisfaction in IBS-C Patients With and Without Diarrhea: Presidential Poster

Abstract

Introduction: Linaclotide has been shown to improve abdominal pain and stool frequency and was well tolerated in phase 3 clinical trials of IBS-C patients. Here we evaluate the most common LIN adverse event (AE), diarrhea, and assess tolerability and treatment satisfaction (Tx Sat) in IBS-C patients (pts) who rolled over (RO) from a phase 3 trial into a long-term study (LTS) of LIN. Methods: Patients meeting modified Rome II IBS-C criteria were randomized to oral 290 μg LIN or placebo (PBO) qd in a 6-month phase 3 trial. RO pts completed phase 3 and entered an open-label 18-month LTS. Treatment satisfaction (not at all, a little, moderately, quite, very satisfied) and AEs, including any reports of diarrhea, were recorded at all study visits; AE severity was assessed based on pt description. In the LTS, pts could suspend, reduce (145 μg), or withdraw from dosing due to AEs. Treatment satisfaction was assessed in pts with and without diarrhea. Results: Of 535 IBS-C RO pts in the 18-month LTS, 79% had ≥1 AE; 45 pts (8%) withdrew due to an AE. Diarrhea, the most common AE (171 pts; 32%; 0.29/pt-year), was mostly mild or moderate in severity and led to withdrawal in 18 pts (3%) (Table). There were no diarrhea-related SAEs. 131 patients (24%) decreased and/or suspended their LIN dose due to diarrhea; the majority of these patients completed the study (Table). Pts averaged at least moderate Tx Sat; >70% of pts were moderately to very satisfied with LIN treatment regardless of whether they had diarrhea (Figure 1).Figure 1Conclusion: During up to 2 years on LIN, IBS-C pts were moderately to quite satisfied with treatment on average, and LIN was well tolerated. Diarrhea AEs, reported in 32% of IBS-C pts in the 18-month LTS, were generally mild or moderate in severity, easily managed, and infrequently led to study withdrawal. IBS-C pts who reported diarrhea on LIN had similar Tx Sat relative to those who did not report diarrhea. (Studies sponsored by Forest Laboratories, Inc., and Ironwood Pharmaceuticals, Inc.)Table 1: Characterization of Diarrhea in IBS-C Pats on LIN Who Completed a Ph3 Trial and RO Into an LTSDisclosure - William Chey is a paid consultant for Astra Zeneca, Asubio, Astellas, Entera, Furiex, Ironwood, Forest, Merck, Prometheus, Salix, SK, Sunovian, Sucampo, and Takeda, and receives research grants from Coulter Foundation, Ironwood, Nestle, Perrigo, and Prometheus. Steve Shiff is an employee of Forest Research Institute, Inc. and own stock and/or stock options in Forest Laboratories, Inc. Harvey Schneider is a consultant to Forest Research Institute, Inc. Xinming Hao, Bernard Lavins, Jennifer Chickering, Mark Currie, and Jeffrey Johnston Taylor are employees of Ironwood Pharmaceuticals, Inc. and own stock and/or stock options in Ironwood Pharmaceuticals. This research was supported by an industry grant from Forest Research Institute and Ironwood Pharmaceuticals.