Real-World Comparison of Elobixibat and Lubiprostone Treatment in Patients with Chronic Constipation: A Propensity Score-Matched Analysis

Abstract

Introduction: Elobixibat is a new laxative, but its efficacy and adverse events (AEs) are insufficiently examined compared with those of other laxatives. Hence, by propensity score (PS) matching, we compared the effects and AEs between elobixibat and lubiprostone. Methods: We retrospectively analyzed 1887 Japanese patients with chronic constipation (CC) treated at our hospital between October 2013 and April 2020. Enrolled patients were divided into three treatment groups, namely, elobixibat (10 mg daily) (E10 group, n = 293), lubiprostone (24 mcg daily) (L24 group, n = 772), and lubiprostone (48 mcg daily) (L48 group, n = 822), as their first treatment. We then investigated the changes on the weekly average number of spontaneous bowel movements (SBMs), Stool Consistency Scores (SCSs), and AEs starting from the baseline until the end of the 2-week treatment. To adjust for patient background, we performed one-to-one nearest neighbor matching without replacement between elobixibat- and lubiprostone-treated patients according to the individual estimated PSs. Results: After treatment, for SCSs, both the L24 and L48 groups significantly improved compared with the E10 group (p < 0.05), but their stools were soft (Bristol stool form scale: 4.8). Notably, the E10 group had less frequent AEs than the L24 group (26 [9.0%] vs. 43 [14.8%], p = 0.03). Particularly, nausea was significantly less in the E10 group than in the L48 group (2 [0.7%] vs. 7 [2.4%], p = 0.01). Conclusion: Elobixibat is a beneficial drug for patients with mildly symptomatic CC and is safe to use, given its few AEs.

Safety of elobixibat and lubiprostone in Japanese patients with chronic constipation: a retrospective cohort study

“…Second, the follow-up period was approximately 3 months in our study; the events that might occur after a long-term will be missed. However, several studies on laxatives (including elobixibat and lubiprostone) have been conducted with a short period of observation (less than 3 months) [15,16,26,29,34]. Third, the proportion of reported events such as diarrhea and abdominal pain might be slightly underestimated in our study as they may differ depending on whether the study population included elderly individuals or not.…”

“…Patients diagnosed with cancer or Parkinson's disease were not included in the clinical trials [26,29]. In addition, although the main population in our study was an elderly population, populations in most previous studies [16,18,26,28,29] included only a few elderly individuals, except for some observational studies [15,27,32].…”

“…There are a few studies that have made a head-to-head comparison of elobixibat and lubiprostone. In a retrospective cohort study with 2-week follow-up using propensity score matching by Eguchi et al [15], any adverse events due to elobixibat (9%) with a daily dose of 10 mg were significantly less than those due to lubiprostone (14.8%) with a daily dose of 24 μg (p = 0.03); the incidence of nausea caused by lubiprostone with a daily dose of 48 μg was approximately three times greater than that by elobixibat with a daily dose of 10 mg (p = 0.01). These findings are relatively consistent with our findings, although there were some differences in the observation period with the follow-up period of 3 months and methodology using the new-user design [19].…”

“…Lubiprostone has been marketed in some countries, including the United States, whereas elobixibat is authorized only in Japan as of March 2020. In a retrospective cohort study comparing users of elobixibat and lubiprostone [15], the incidence of nausea in users of lubiprostone 48 μg was 3.4 times higher than that in users of elobixibat 10 mg. The incidence of adverse events caused by elobixibat (9%) was significantly lower than that caused by lubiprostone (15%) with a daily dose of 24 μg.…”

Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options

“…Elobixibat is an ileal bile acid transported inhibitor that represents a new class of treatment for CIC patients; its administration causes increased delivery of bile acids to the colon, 49 accelerating large bowel transit and increasing colonic secretion. Elobixibat, in both Phase II 50–52 and Phase III studies 53 , 54 proved to be efficacious and well tolerated even in real-life conditions, 55 with a good safety profile even in elderly patients, 56 suggesting its possible rose as first-line approach to treat patients complaining of CIC. 57 The use of elobixibat is currently approved only in Japan.…”