Khanna, Lehar

Summary Background A subset of patients with chronic constipation has associated slow colonic transit and reduced faecal bile acid excretion. In addition to traditional approaches to treat chronic constipation, a novel therapeutic option is to increase the colonic concentration of intraluminal bile acids. This can be achieved through inhibition of the ileal bile acid transporter. Aim To evaluate the evidence for efficacy and safety of an ileal bile acid transport inhibitor in the treatment of chronic constipation Methods We reviewed published literature on elobixibat, based on a PubMed search. Results Elobixibat is a novel ileal bile acid transport inhibitor that has demonstrated efficacy in proof of concept studies in experimental animals as well as phase 1, 2 and 3 trials in humans. Phase 4 studies have now documented that the beneficial effects are related to increase in the secretory bile acids in the colon as measured by stool bile acid content. The studies documented efficacy in patients with severe constipation, which is often associated with slow colonic transit. These changes in bile acid composition were associated with minor differences in the faecal microbiota in patients treated with elobixibat compared to placebo. Elobixibat appears to be safe. The only adverse effects of note are associated with its pharmacological actions in patients with chronic constipation,namely the induction of diarrhoea and abdominal pain. Conclusion This new class of compound appears to be safe and efficacious in the treatment of chronic constipation.

LINKED CONTENTThis article is linked to Khanna & Camilleri and Tobi et al papers. To view these articles, visit https://doi.org/10.1111/apt.16143 and https://doi.org/10.1111/apt.16270

SummaryBackgroundTradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV).AimTo evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics.MethodsWe conducted a randomised, double‐blind, placebo‐controlled, single‐centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2.ResultsThe two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV.ConclusionTradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis.Clinic trials registryClinicalTrials.gov #NCT04849559.

Abstract Background Most prevalent gastrointestinal symptoms in multiple sclerosis (MS) relate to lower bowel dysfunction, often in association with bladder manifestations. Objective To assess clinical and objective gastrointestinal motor dysfunctions in patients with MS. Methods This was a single‐center, retrospective study of 166 patients evaluated between 1996 and 2020. We reviewed characterization of the MS, gastrointestinal and neurological symptoms, measurements of gastrointestinal and colonic transit, and anorectal manometry. Key Results At the time of the gastrointestinal evaluations of the 166 patients with MS (138 women; 83%), 111 were in the relapsing‐remitting phase and 52 were in the progressive phase. In 3 patients, disease phase was not assigned due to insufficient data. Constipation was identified in 82% (136/166) of patients. Most [103/116 (88%)] patients with bladder symptoms also had constipation or fecal incontinence. Delayed gastric emptying at 4 h and colonic transit at 24 h was identified in 16% and 7% of the cohort, respectively; 22% had accelerated gastric emptying. On anorectal manometry, resting anal sphincter pressure >90 mm Hg and rectoanal pressure differential below −50mm Hg suggested evacuation disorder in patients with constipation. Conclusions and Inferences In addition to slow colonic transit and anorectal dysfunction leading to constipation in MS, 22% of patients had accelerated gastric emptying.

AbstractBackgroundAspiration pneumonia is the commonest cause of hospitalizations and death in patients with Parkinson's disease (PD). Among these patients, the relationships between severity of dysphagia, hospitalizations for related complications, and death are not robustly defined. Our aim was to characterize the relationship between PD‐related oropharyngeal dysfunction and clinically relevant outcomes.MethodsRetrospective cohort study of 312 patients with PD at a tertiary center who underwent videofluoroscopic swallow studies conducted by expert therapists between 2010 and 2015. Level of swallowing function was represented using the 7‐point Functional Oral Intake Scale (FOIS) (7 = normal function). Significance and relative risk calculations utilized Poisson regression. Time to composite outcome of first hospitalization or death was summarized using Kaplan‐Meier curve with log‐rank test.Key ResultsOne hundred thirty eight patients had a recorded FOIS score. The prevalence of oropharyngeal dysfunction was 76.1%. The median duration of follow‐up was 26.8 months. In multivariate analyses, patients with FOIS 5 (RR = 2.01 [95% CI: 1.22, 3.32]), FOIS 3 (RR = 2.78 [95% CI: 1.75, 4.40]), and FOIS 1 (RR = 2.50 [95% CI: 1.49, 4.20]) were significantly associated with increased risk of hospitalization or death compared to FOIS 7 after co‐variate adjustments. GERD was also associated with a significant increased risk of hospitalization or death (RR = 1.28 [95% CI: 1.01, 1.64]). Time to first hospitalization or death was shorter in patients with lower FOIS scores (p < 0.00005).Conclusions and InferencesSeverity of oropharyngeal dysphagia, as measured by the FOIS, is associated with poorer survival and shorter time to hospitalization for dysphagia‐related complications, pneumonia, or death in PD.