A multicenter, postmarketing surveillance of elobixibat in patients with chronic constipation in Japan: A final analysis report

Abstract

Objective: An interim analysis of postmarketing surveillance reported the safety and efficacy of elobixibat, a laxative medication that inhibits the ileal bile acid transporter, at 4 weeks in approximately 1000 patients with chronic constipation in Japan. However, its long-term safety and efficacy in elderly patients remain unclear. This study aimed to conclude and report the final analysis of postmarketing surveillance, including 52-week safety and efficacy profiles in a clinical practice setting, using approximately 3000 patients.

Methods: The overall survey period spanned from June 2018 to May 2022. Observation periods were set at 4 weeks (4-week treatment period) and 52 weeks (52-week treatment period). Adverse drug reactions and efficacy outcomes, including defecation frequency, Bristol Stool Form Scale scores, and patient satisfaction, were analyzed.

Results: The 4-week safety analysis set included 3638 patients with a mean age of 70.8 years, and 73.7% were aged ⩾65 years. Most patients (62.5%) were treated with elobixibat alone, while the rest received concomitant laxatives. In total, 231 patients (6.35%) experienced adverse drug reactions, with gastrointestinal disorders (6.02%) such as diarrhea (3.35%) and abdominal pain (2.06%), being the most common adverse drug reaction. The adverse drug reaction incidence in elderly patients aged ⩾65, ⩾75, and ⩾85 years was 5.49%, 4.85%, and 2.80%, respectively. In the 52-week treatment period, adverse drug reaction incidence was 5.40% (71/1315 patients), similar to that in the 4-week treatment period. Regarding efficacy, defecation frequency and Bristol Stool Form Scale scores significantly improved from week 2 onward, regardless of the age group and administration timing (before breakfast, lunch, or dinner). Most patients reported satisfaction from week 2 onward (6.0%, 66.9%, 78.6%, and 90.4% at baseline, weeks 2, 4, and 52, respectively).

Conclusion: This study confirmed the long-term safety and efficacy of elobixibat in patients with chronic constipation, including many elderly ones, in routine clinical practice.

Keywords: Elobixibat; chronic constipation; efficacy; long term; postmarketing surveillance; safety.

Figure 1.

Patient disposition.

Figure 2.

Time course of defecation frequency per week in 4-week treatment (4WT) and 52-week treatment (52WT) in the overall population (all age groups). Mean ± standard deviation. BL: baseline; N: number. *p < 0.0001 versus baseline.

Figure 3.

Time course of Bristol Stool Form Scale (BSFS) score distribution in 4-week treatment (4WT) and 52-week treatment (52WT) in the overall population (all age groups). The number in parentheses on the X-axis represents the number of patients. BL: baseline; W: week.

Figure 4.

Time course of patient satisfaction assessment in 4-week treatment (4WT) and 52-week treatment (52WT) in the overall population (all age groups). The numbers below the treatment period on the X-axis represent the number of patients. BL: baseline; W: week.

Figure 5.

Time to defecation after elobixibat administration before breakfast and dinner in 4-week treatment (a) and 52-week treatment (b). N: number of patients who reported the time.

Figure 6.

Cumulative proportion of combination drug withdrawal estimated using the Kaplan–Meier method.