Introduction Linaclotide (LIN) has been shown to improve abdominal pain and stool frequency and was well tolerated in Phase 3 clinical trials of patients (pts) with irritable bowel syndrome with constipation (IBS-C). Here we evaluate the most common LIN adverse event (AE), diarrhoea, and assess tolerability and treatment satisfaction (Tx sat) in IBS-C pts who rolled over (RO) from a Phase 3 trial into a long-term study (LTS) of LIN.
Method Pts meeting modified Rome II IBS-C criteria were randomised to oral 290 µg LIN or placebo daily in a 6 month Phase 3 trial. RO pts completed Phase 3 and entered an open-label 18 month LTS. Tx sat (not at all, a little, moderately, quite, very) and AEs, including any reports of diarrhoea, were recorded at all study visits; AE severity was assessed by the investigator based on pt description. In the LTS, pts could interrupt, reduce (145 µg) or withdraw from dosing due to AEs. Tx sat was assessed in pts with and without diarrhoea.
Results Of 535 IBS-C RO pts in the LTS, 79% had ≥1 AE; 45 pts (8%) withdrew due to an AE; 24 pts (4.5%) reported ≥1 serious AE (SAE). Diarrhoea, 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 1]. There were no diarrhoea-related SAEs. 131 pts (24%) decreased and/or interrupted their LIN dose due to diarrhoea; the majority of these pts continued in the study (Table 2). Pts averaged at least moderate Tx sat; >70% of pts were moderately to very satisfied with LIN treatment regardless of whether they had diarrhoea (figure 1).
Conclusion During up to 2 years on LIN, IBS-C pts were moderately to quite satisfied with treatment on average. Diarrhoea AEs were generally mild or moderate in severity and infrequently led to study withdrawal. TX sat was similar in LIN-treated pts who did and did not report diarrhoea. LIN was well tolerated.
Disclosure of Interest H. Schneier: None Declared, S Shiff Conflict with: Allergan plc, Conflict with: Allergan plc, X Hao Conflict with: Ironwood Pharmaceuticals, J Chickering Conflict with: Ironwood Pharmaceuticals, Conflict with: Ironwood Pharmaceuticals and Allergan plc, Conflict with: Ironwood Pharmaceuticals, C Kurtz Conflict with: Ironwood Pharmaceuticals, M Currie Conflict with: Ironwood Pharmaceuticals, Conflict with: Ironwood Pharmaceuticals, J Johnston Conflict with: Ironwood Pharmaceuticals, Conflict with: Ironwood Pharmaceuticals
- treatment satisfaction
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