PTH-195Lubiprostone Treatment Improves Constipation and Related Symptoms in Patients Refractory to other Constipation Therapies

IntroductionConstipation affects millions globally; however, many patients are dissatisfied with currently-available laxative treatments, with most interested in access to other treatment options1. Lubiprostone (24 mcg BID) has been shown to be effective and well-tolerated in patients with refractory constipation.MethodsPost-hoc analysis was conducted to evaluate whether lubiprostone provides relief in patients who are refractory or lacking adequate relief from other common constipation therapies. Pooled patient and medication data from two pivotal trials were assessed. Patients with a history of constipation despite the use of constipation medication during the 90 days prior to initiation of study medication were included. Response rates and symptomatic improvements in this subpopulation of refractory patients were analysed based on treatment assignment in the clinical trial: lubiprostone (24 mcg BID) or placebo. Analysis was performed on the whole and by the class of prior medication usage. Patients were considered full responders if they achieved greater than or equal to 4 spontaneous bowel movements (SBMs)/week. Patients achieving greater than or equal to 3 but < 4 SBMs/week were moderate responders; those with < 3 SBMs/week were non-responders. Symptomatic improvements were also assessed.ResultsFull response to treatment ranged from 52.8 to 67.2% across the 4 weeks of treatment, as compared to 32.3% to 47.4% for placebo patients. For patients who were moderate responders, response rates increased to 64.8-80.0% among the lubiprostone treatment group compared to only 46.6-57.9% of placebo patients. Lubiprostone produced a significant and full response over placebo, respectively, among the refractory patients who previously took contact laxatives 50.9-64.9% vs. 21.3-42.6%; PEG solutions 57.5-75.0% vs. 32.5-52.5%; or enemas 50.0-71.4% vs. 23.3-50.0%. For symptoms of constipation such as stool consistency and straining, lubiprostone treatment resulted in statistically significant improvements compared to placebo at each study week (p less than or equal to 0.001). In particular, lubiprostone statistically significantly improved overall stool consistency among patients who previously used contact laxatives (p less than or equal to 0.001), enemas (p less than or equal to 0.007) or PEG solutions (p less than or equal to 0.003) at all treatment weeks. Statistically significant improvements in straining were seen at all treatment weeks in patients who previously