Introduction 

Constipation is highly prevalent in the elderly population and linked to lower quality of life. Straining, due to constipation, can lead to myocardial infarction, heart failure, and stroke in the elderly. Osmotic therapy and stimulant laxatives have not been effective. Elobixibat is a first-in-class selective ileal bile acid transporter inhibitor, approved for use in chronic idiopathic constipation. Studies have shown that elobixibat is safe (long-term data) and effectively improves the frequency of spontaneous bowel movements (SBMs), time to the first SBM, and stool form in chronic constipation, but frequently linked to abdominal pain, and diarrhea. There is lack of data on its efficacy in the elderly, patients with comorbidities which could cause chronic constipation, and patients with previous and concomitant use of other laxatives. Furthermore, apart from dose administration before breakfast, the efficacy of elobixibat when administered before lunch or dinner, is unknown. 

Aim

To evaluate the safety and efficacy of elobixibat in elderly patients with chronic constipation and compare the efficacy according to administration time

Patient Profile 

Method

Study Design

• An interim analysis of a prospective, multi-center, post-marketing surveillance 
• A once-daily oral dose of elobixibat 10 mg was administered before any meals for 4 weeks; dose was reduced (5 mg) or increased (15 mg) as per physician’s discretion
• The study was extended up to 52 weeks for patients who received the drug for >5 weeks

Endpoints

• Efficacy outcomes: mean number of bowel movements, stool form based on the Bristol Stool Form Scale (BSFS) scores, patient satisfaction with bowel movements, abdominal distension, straining during defecation, presence/absence of fecal disimpaction, and time to bowel movement at Weeks 2 and 4
• Subgroup analyses were conducted to evaluate effects of old age, administration of elobixibat before any meals, elobixibat monotherapy, and severity of constipation
• Safety outcomes: incidence, types, severity, period of occurrence and outcomes of adverse drug reactions (ADRs) and causal relationship and severities of ADRs 

Results 

Efficacy 

• Elobixibat significantly improved the mean bowel movements per week from baseline to Week 2 and Week 4 (P < 0.001, for both) (Figure 1)
• The mean BSFS score significantly increased with elobixibat therapy as compared to baseline (3.8 at Week 2 and 3.9 at Week 4 vs. 2.3, P < 0.001 for both)
• Patient satisfaction with bowel movements was higher with elobixibat, whereas, bloating or straining during bowel movements was lower at Weeks 2 and 4 versus baseline (Table 1)
• The mean time to bowel movement was 6.1 hours at Week 2 and 6.4 hours at Week 4
• Elobixibat lowered fecal disimpaction at Week 2 (4.1%) and Week 4 (3.4%) versus baseline (11.4%)
• It significantly increased the bowel movements in the elderly and subpopulations at Weeks 2 and 4 (P < 0.001, for both) versus baseline
• Elobixibat significantly improved the mean BSFS score in patients aged ≥65 years (baseline 2.3 vs. 3.7 and 4.0 at Weeks 2 and 4, P < 0.001) as well as in those aged ≥75 years (baseline 2.3 vs. 3.7 and 3.9 at Weeks 2 and 4, P < 0.001)
• The mean number of bowel movements per week significantly increased at Weeks 2 and 4 in a subgroup of patients who were prescribed elobixibat before breakfast and dinner and at Week 4 in those who were prescribed the drug before lunch
• Elobixibat significantly increased the mean BSFS score at Week 4 in all subpopulations (P < 0.001)
• The patients who received the drug before breakfast most commonly showed a time to bowel movement of 3-5 hours, whereas those who received the drug before dinner showed 3-5 hours and 12-14 hours. 
• In the subgroups of elobixibat monotherapy, severe or very severe constipation, higher mean number of bowel movements per week were achieved at Weeks 2 and 4 than at baseline (P < 0.001)
• The BSFS score was close to the ideal score (Type 4) at Weeks 2 and 4; it was significantly higher at Weeks 2 and 4 than at baseline (P < 0.001)

Figure 1: Effect of elobixibat treatment on bowel movements in study patients

Table 1: Effect of elobixibat treatment on patient satisfaction and symptoms of constipation

Safety   

• Elobixibat was associated with ADRs in 5.24% patients; diarrhea (2.19%) and abdominal pain (1.81%) were commonly reported
• A serious ADR of death was reported in one patient (0.10%); however, the cause of death was not provided
• The incidence of ADRs in the ≥ 65-year-old or ≥ 75-year-old subpopulation was similar to that seen in the total patient population
• The subgroup analysis for ADR in the patients treated with no prior or concomitant drugs suggested that there was a similar incidence of ADRs in patients treated with elobixibat alone and those treated with prior or concomitant laxatives

Conclusion 

Elobixibat was well-tolerated and efficacious in elderly patients with chronic constipation and can be administered before any meals.

J Neurogastroenterol Motil. 2022; 28: 431-441