Durability of Response of Lubiprostone in the Treatment of Chronic Idiopathic Constipation

Introduction: Lubiprostone activates type 2 intestinal chloride channels increasing secretion and decreasing transit time and is FDA approved for the treatment of chronic idiopathic constipation (CIC). Pivotal phase 3 studies showed improvement in symptoms over placebo at four weeks. We examined a cohort of patients to assess durability of response. Methods: Electronic medical records of 100 patients with a diagnosis of CIC who were treated with lubiprostone were reviewed retrospectively. Patients with an initial response and a minimum follow up time of 6 months were included. Response was defined as greater than or equal to three complete and spontaneous bowel movements per week and a Bristol stool scale score of 3 to 4. Patients who had a BSS of less than 3 or required dose adjustments during the initial 4 months of treatment were excluded. Data for gender, age, length of time on drug, change of dose or frequency, and need for rescue medication at any time were collected. Data were summarized with Microsoft Excel 14.6. Results: The median age was 54.5 (range 27-88). 74% (20/27) were female and 26% (7/27) were male. Mean total follow up time was 21.8 months (range 6 to 48 months). 22 of 27 patients (81.5%) maintained response at the time of last follow up. The patients who lost response all required laxatives for adjunctive therapy by month 10. Of the 22 patients with long term response: - 4 began lubiprostone following intolerance to linaclotide (diarrhea) - 1 stopped after 14 months without recurrent symptoms. - 1 switched to 24 μg every other day. - 1 switched 24 μg daily alternating with 24 μg bid. - 1 patient was symptom free for 18 months and developed recurrent symptoms after stopping the medication. After resumption, symptoms have resolved with 30 months of follow up. - 2 patients who were started on 8 μg bid changed to 24 μg bid. - 2 patients have maintained long-term relief by using it as on demand therapy. No significant adverse events were observed. Conclusion: 1. Lubiprostone maintains improvement of constipation symptoms in 81.5% of initial responders over a mean follow up of 21.8 months. 2. Approximately one third of patients required individualized dose adjustment for continued relief. 3. As with phase 3 studies, long-term lubiprostone use was well tolerated in this cohort. 4. For patients with diarrhea on linaclotide, lubiprostone may be an effective alternative.