Efficacy of elobixibat for elderly patients with chronic constipation in a clinic

Abstract

BACKGROUND

Elobixibat reportedly improves bowel movements in patients with chronic constipation. However, its effect on bowel movements in elderly patients with chronic constipation in clinical settings has not been examined.

AIM

To examine bowel movement frequency and stool form before and after elobixibat administration in elderly patients with chronic constipation at our clinic.

METHODS

A total of 10 mg elobixibat was administered to 35 (< 65 years old) patients and 45 (≥ 65 years old) patients with chronic constipation. The frequency of bowel movements and stool forms, assessed using the Bristol Stool Form Scale (BSFS), were compared between the two groups 1 week before and after elobixibat administration.

RESULTS

In patients aged < 65 years with chronic constipation, the pre-elobixibat frequency of bowel movements and BSFS scores were 2.167 ± 0.732 and 2.286 ± 0.742, respectively. After elobixibat administration, the frequency of bowel movements and BSFS scores improved to 2.389 ± 0.502 and 3.995 ± 0.566, respectively, showing a significant improvement in bowel movement status. In patients aged ≥ 65 years with chronic constipation, the pre-elobixibat frequency of bowel movements and BSFS scores were 2.003 ± 0.733 and 2.217 ± 0.758, respectively. After elobixibat administration, the frequency of bowel movements and BSFS scores improved to 4.402 ± 1.346 and 3.800 ± 0.704, respectively, indicating an improvement in bowel movement status (P < 0.001). No significant differences were observed in the frequency and improvement status of bowel movements or BSFS scores between patients with chronic constipation aged ≥ 65 years and < 65 years. Adverse events due to the administration of elobixibat occurred in 16 cases (20%). No significant differences were found in the incidence of adverse events between patients with chronic constipation aged < 65 years (8 cases, 22.9%) and those aged ≥ 65 years (8 cases, 17.8%).

CONCLUSION

Elobixibat is effective in improving bowel movement status in patients with chronic constipation. No significant differences were found in the improvement of bowel movement status or the incidence of adverse events between patients with chronic constipation aged < 65 years and ≥ 65 years, suggesting that the drug may be safely used in elderly patients.

Key Words: Bile acid; Elderly patients; Elobixibat; Chronic constipation; Post cholecystectomy; Constipation

Core Tip: Elobixibat was effective in improving bowel movements in patients with chronic constipation. Furthermore, there were no significant differences in treatment efficacy or incidence of adverse events between elderly patients and younger patients with chronic constipation. With its high clinical efficacy in treating chronic constipation in elderly patients and its low incidence of adverse events, elobixibat appears to be a viable treatment option for elderly patients.

INTRODUCTION

With advances in medical care, the global population is rapidly aging[1]. In the elderly, organ function typically declines with age[2,3], leading to reduced immune and infection-protective capabilities and impaired homeostasis. Therefore, elderly individuals are reported to more frequently have underlying diseases as they age[4-7]. To provide medical care, treatment with the best possible, minimally invasive, and highly useful methods is required, with few incidental findings. Incidental findings are more likely to become serious in elderly individuals because of a higher probability of having underlying diseases compared with younger people[4]. Therefore, ensuring that treatments can be performed safely and effectively is extremely important, and various considerations have been implemented to address these concerns[5-7].

A report showed that people with chronic constipation experienced not only a lower quality of life (QOL) and work productivity and activity impairment but also economic loss compared to healthy individuals[8]. Chronic constipation is also known to easily cause defecation syncope due to excess straining during defecation, which places a burden on the cardiovascular system[9]. Moreover, chronic constipation can lead to changes in intestinal metabolites due to abnormal intestinal microflora, which may be associated with the development of various diseases, including arteriosclerosis and cardiovascular diseases[10]. A report indicated that a lower frequency of bowel movements increased the risk of mortality due to cardiovascular diseases[11], and improvement of chronic constipation is extremely important for human life. As diet/exercise therapy can be challenging for elderly patients with chronic constipation, pharmacotherapy is often highly anticipated. In drug therapy, there are drugs with various mechanisms of action, and their usefulness has been reported[12-16]. Elobixibat is the world's first bile acid transporter inhibitor. It works by inhibiting ileal bile acid transporters (IBATs), which are expressed on the epithelial cells of the distal ileum. This inhibition results in increased bile acid flow into the large intestine, promoting large intestinal fluid secretion and peristaltic movement, thereby improving bowel movement status[17-23]. To our knowledge, there have been only a few studies on the use of elobixibat in elderly patients with chronic constipation[21-23]. However, it is difficult to say that elobixibat has been sufficiently studied, as there are no reports on its evaluation in clinics despite its widespread use. In this study, we aim to assess the usefulness and safety of elobixibat in elderly patients with chronic constipation at our clinic.

MATERIALS AND METHODS

Our study included 80 patients diagnosed with chronic constipation at our clinic from May 2018 to November 2024. Rome IV criteria were used to diagnose chronic constipation[24]. Elobixibat administration was compared and examined between 35 (< 65 years old) patients and 45 (≥ 65 years old) patients with chronic constipation. None of the patients had undergone ileectomy. Stool forms were assessed using Bristol Stool Form Scale (BSFS)[25]. The inclusion criteria were: (1) Patients diagnosed with chronic constipation based on the Rome IV criteria; (2) Patients who were 20 years old or older at the time of diagnosis; and (3) Patients who presented to the hospital as outpatients. The exclusion criteria were: (1) Patients diagnosed with temporary constipation; (2) Patients with extremely poor general condition; and (3) Patients whom the study doctor deemed ineligible. A total of 10 mg elobixibat was administered before the evening meal. Changes in the frequency of bowel movements and stool forms, 1 week before and after elobixibat administration, were examined.

Data for this study were used after obtaining prior consent from all patients. The use of the study data was reviewed upon our request and approved by the ethical committee of Kimitsu Central Hospital (institutional review board No. 802; Kisarazu, Japan).

Statistical analyses

Between-group comparisons were performed using Wilcoxon single-rank test, paired t-test, χ² test, and F-test. P < 0.05 was considered statistically significant. The software used was Statistical Package for the Social Sciences (version 17; IBM SPSS Statistics, Armonk, NY, United States).

RESULTS

Patient backgrounds are summarized in Table 1. The study included 29 men and 51 women, with a mean ± SD age of 66.156 years ± 13.961 years. Stool types assessed using BSFS were as follows: (1) Type 1 (18 patients); (2) Type 2 (32 patients); (3) Type 3 (30 patients); (4) Type 4 (0 patients); (5) Type 5 (0 patients); (6) Type 6 (0 patients); and (7) Type 7 (0 patients). The frequency of bowel movements 1 week before elobixibat administration was 2.013 ± 0.639. The number of drugs used to relieve chronic constipation before elobixibat administration was 0 in 28 patients, 1 in 30 patients, and 2 in 20 patients. Table 2 shows the background of patients with chronic constipation (< 65 and ≥ 65 years old). In patients aged ≥ 65 years with chronic constipation, there was a significantly higher prevalence of hypertension, diabetes mellitus, dyslipidemia, cardiac disease, and renal disease. Table 3 shows the effects of elobixibat administration. A comparison of data from 1 week before and after elobixibat administration revealed significant improvements in both the frequency of bowel movements and stool forms. In both groups (< 65 years old and ≥ 65 years old) of patients with chronic constipation, the frequency of bowel movements and stool forms were significantly improved 1 week after elobixibat administration, compared with those 1 week before administration. No significant differences were found in the improvement of bowel movement frequency or stool forms with elobixibat administration between patients with chronic constipation aged < 65 years and those aged ≥ 65 years (Table 4). Table 5 shows the adverse events due to elobixibat administration. Sixteen cases (20%) of adverse events were observed: (1) eight cases (10%) of abdominal pain; and (2) eight cases (10%) of diarrhea. One patient (1.3%) experienced frequent diarrhea and discontinued the oral treatment 3 days after administration. Other adverse events were mild and resolved with conservative treatment, allowing the continuation of treatment. No significant differences were found in the incidence of adverse events due to elobixibat administration between the patients with chronic constipation aged < 65 years and those aged ≥ 65 years.

Table 1 Patient characteristics, n (%).

Number of patients	n = 80
Sex
Male	29 (36.3)
Female	51 (63.8)
Age	66.156 ± 13.961
Bristol Stool Form Scale
Type 1	18 (22.5)
Type 2	32 (40)
Type 3	30 (37.5)
Type 4	0 (0)
Type 5	0 (0)
Type 6	0 (0)
Type 7	0 (0)
1-week frequency of bowel movements before elobixibat administration	2.013 ± 0.639
Number of drugs to relieve constipation before elobixibat administration
0	28 (35)
1 magnesium oxide tablet	32 (40)
2 magnesium oxide tablets + sennoside	20 (25)
Comorbidity
Hypertension	38 (47.5)
Hyperlipidemia	36 (45)
Diabetes mellitus	35 (43.8)
Cerebrovascular disease	16 (20)
Chronic respiratory disease	13 (16.3)
Cardiac disease	22 (27.5)
Chronic hepatic disease	18 (22.5)
Chronic renal disease	10 (12.5)
Malignant disease	6 (7.5)
Post cholecystectomy	18 (22.5)

Table 2 Comparison of patient backgrounds by age, n (%).

	< 65 years old	≥ 65 years old	P value
Number of patients	35	45
Sex
Male	12 (34.3)	17 (37.8)	0.8171
Female	23 (65.7)	28 (62.2)	0.8171
Age	52.563 ± 9.648	76.023 ± 6.341	< 0.001
Pre-elobixibat defecation count/1-week frequency	2.167 ± 0.732	2.003 ± 0.733	0.9631
Pre-elobixibat Bristol Stool Form Scale/1-week score	2.286 ± 0.742	2.217 ± 0.758	0.8960
Number of drugs to relieve constipation before elobixibat administration
0	11 (31.4)	17 (37.8)	0.6397
1 magnesium oxide tablet	13 (37.1)	19 (42.2)	0.8183
2 magnesium oxide tablets + sennoside	7 (20)	13 (28.9)	0.0536
Comorbidity
Hypertension	10 (28.6)	28 (62.2)	0.0035
Hyperlipidemia	8 (22.9)	28 (62.2)	< 0.001
Diabetes mellitus	9 (25.7)	26 (57.8)	< 0.001
Cerebrovascular disease	5 (14.3)	11 (24.4)	0.3987
Chronic respiratory disease	3 (8.6)	10 (22.2)	0.1319
Cardiac disease	5 (14.3)	17 (37.8)	0.0241
Chronic hepatic disease	5 (14.3)	13 (28.9)	0.1775
Chronic renal disease	1 (2.9)	9 (20)	0.0370
Malignant disease	2 (7.7)	4 (8.9)	0.6945
Post cholecystectomy	6 (17.1)	12 (26.7)	0.4203

Table 3 Changes in bowel movements before and after elobixibat administration.

Total: 80 cases		Comparison before and after elobixibat administration (P value)
Pre-elobixibat defecation count/1-week frequency	2.013 ± 0.639
Post-elobixibat defecation count/1-week frequency	4.394 ± 1.346	< 0.001
Pre-elobixibat BSFS/1-week score	2.181 ± 0.758
Post-elobixibat BSFS/1-week score	3.987 ± 0.855	< 0.001
< 65 years old
Pre-elobixibat defecation count/1-week frequency	2.167 ± 0.732
Post-elobixibat defecation count/1-week frequency	4.375 ± 1.163	< 0.001
Pre-elobixibat BSFS/1-week score	2.286 ± 0.742
Post-elobixibat BSFS/1-week score	3.995 ± 0.566	< 0.001
≥ 65 years old
Pre-elobixibat defecation count/1-week frequency	2.003 ± 0.733
Post-elobixibat defecation count/1-week frequency	4.402 ± 1.346	< 0.001
Pre-elobixibat BSFS/1-week score	2.217 ± 0.758
Post-elobixibat BSFS/1-week score	3.800 ± 0.704	< 0.001

BSFS: Bristol Stool Form Scale.

Table 4 Comparison of changes in bowel movement before and after administration of elobixibat by age.

	< 65 years old	≥ 65 years old	P value
Pre-elobixibat defecation count/1-week frequency	2.167 ± 0.732	2.003 ± 0.733	0.9631
Post-elobixibat defecation count/1-week frequency	4.375 ± 1.163	4.402 ± 1.346	0.7745
Pre-elobixibat BSFS/1-week score	2.286 ± 0.742	2.217 ± 0.758	0.8960
Post-elobixibat BSFS/1-week score	3.995 ± 0.566	3.800 ± 0.704	0.1063

BSFS: Bristol Stool Form Scale.

Table 5 Comparison of adverse events to elobixibat by age, n (%).

	< 65 years old	≥ 65 years old	P value
Adverse events after elobixibat administration of elobixibat
Abdominal pain	4 (11.4)	4 (8.9)	0.7241
Diarrhea	4 (11.4)	4 (8.9)	0.7241
Total	8 (22.9)	8 (17.8)	0.5869

DISCUSSION

Elderly individuals often face multiple underlying diseases, take numerous medications, experience declines in physiological and cognitive functions, and encounter social limitations, which can vary significantly from person to person. In this study, patients with chronic constipation aged ≥ 65 years tended to have significantly more underlying diseases, including hypertension and diabetes mellitus, compared with patients with chronic constipation aged < 65 years. In the elderly, the risks associated with diagnostic tests and treatments can sometimes outweigh the risks posed by the diseases themselves. For individual patients, benefit and harm outcomes should be determined not only objectively but also subjectively, by including QOL improvement, to select an appropriate treatment strategy. There are various treatment methods for chronic constipation; however, pharmacotherapy is often selected for elderly individuals because diet/exercise therapy is usually difficult for them due to reduced dietary intake and the presence of other diseases. Pharmacotherapy is a minimally invasive treatment method and is easy to administer to elderly individuals. Elobixibat, the test drug in this study, inhibits IBATs in the distal ileum to suppress reabsorption of bile and increases the amount of bile acid flowing into the large intestine. Accordingly, the action of bile acid promotes intestinal fluid secretion and peristaltic movement, which increases the frequency of bowel movements and improves stool forms, as reported[17-23]. Improvements in QOL have also been reported[18].

In this study, increased frequency of bowel movements and stool form improvement were observed after elobixibat administration to patients with chronic constipation. Even elderly individuals could be effectively treated, showing no significant differences in the improvement of bowel movement frequency and stool form compared to younger patients. This drug is characterized by inhibiting IBATs to flow a large amount of bile acid into the large intestine, resulting in improved bowel movements. Considering the mechanism of action, when the bile flow to the duodenum is slow, the effects of drugs may be difficult to detect. Sufficient effects may not be observed in patients with child C hepatic cirrhosis and decreased liver function, or in patients with obstructive jaundice[20]. In patients with a history of ileectomy, IBATs are expressed in the distal ileum, and thus, the effects of this drug are less likely to occur. It should be noted that elderly people are likely to have a history of surgery and/or gallbladder stone and choledocholithiasis, which may cause obstructive jaundice. Adverse events due to the administration of elobixibat were observed in 16 patients (20%). Previous reports have indicated that there were no deaths caused by the administration of this drug[17-21]. In our study, eight cases (10%) of abdominal pain and eight cases (10%) of diarrhea were observed. However, there were no serious adverse events that rapidly worsened the patients' general condition; discontinuation of elobixibat occurred in one patient (1.3%) due to frequent diarrhea. Other adverse events were minor and no serious adverse events were observed, suggesting that elobixibat is safe to use. Additionally, its once-daily dosing frequency reduces the likelihood of missed doses compared to treatment drugs that require multiple daily administrations.

This study had several limitations. It was conducted at a single clinic, resulting in a small sample size and a retrospective design. Furthermore, the study only examined results 1 week after administration. Long-term use of constipation treatments may pose a risk of drug resistance, making long-term prognosis a critical consideration[26]. Going forward, a multicenter prospective study with long-term follow-up is necessary. It remains unclear which specific types of chronic constipation may benefit most from elobixibat or which additional drugs should be co-administered with elobixibat to enhance its effectiveness. Continuing this discussion and further research are essential to address these questions.

CONCLUSION

Elobixibat has been useful in treating chronic constipation. Furthermore, there were no significant differences in treatment efficacy or incidence of adverse events between elderly patients and younger patients with chronic constipation. With its high clinical efficacy in treating chronic constipation in elderly patients and its low incidence of adverse events, elobixibat appears to be a viable treatment option for elderly patients.