Alimentary Pharmacology & Therapeutics最新文献

Background: Predose trough concentrations (C_trough) of intravenous infliximab (IV-IFX) during maintenance therapy are associated with therapeutic outcomes in patients with Crohn's disease (CD). A subcutaneous formulation of infliximab (SC-IFX) has shown high C_trough values due to its favourable pharmacokinetics.

Aims: To evaluate the association of C_trough of SC-IFX with therapeutic outcomes and the threshold of SC-IFX C_trough for achieving mucosal healing (MH) and transmural healing (TH) in patients with CD.

Methods: We performed this cross-sectional study in patients with CD who had received SC-IFX maintenance therapy for ≥ 6 months. We measured SC-IFX C_trough immediately before SC-IFX injection. We performed ileocolonoscopy/single-balloon enteroscopy and/or magnetic resonance enterography within 3 months of SC-IFX C_trough measurement. MH was defined as SES-CD-ulcerated surface subscore of 0. TH was defined as simplified MaRIA score of 0.

Results: We enrolled 124 patients with MH in 77.9% (74/95) and TH in 36.3% (37/102). SC-IFX C_trough was significantly higher in patients with MH (24.1 vs.16.9 μg/mL; p = 0.001) and TH (26.0 vs. 20.5 μg/mL; p = 0.007) than in those without. ROC analysis identified that the threshold of SC-IFX C_trough for MH and TH were 17.5 and 30.3 μg/mL, respectively. Multivariate logistic regression showed that SC-IFX C_trough was significantly associated with MH (OR 1.16; 95% CI 1.05-1.27; p = 0.002) and TH (OR 1.08; 95% CI 1.02-1.14; p = 0.005).

Conclusions: SC-IFX C_trough was positively associated with MH (≥ 18 μg/mL) and TH (≥ 30 μg/mL) in patients with CD, which may guide treatment decisions to optimise therapeutic response in the era of treat-to-target.

Background: The worldwide prevalence of inflammatory bowel disease (IBD) is increasing, with its potential evolution as a global disease and a consequent increase in its burden on healthcare systems. These estimates do not factor in the 'real' price of IBD, which, beyond curbing career aspirations, instilling social stigma, and impairing the quality of life in patients, could also significantly affect the environment.

Aim: To highlight potential areas for intervention and develop management strategies aimed at minimising environmental impacts in the field of IBD over time.

Methods: Various aspects of IBD care (organisation of IBD centres, diagnostics and therapeutics) are examined from an environmental sustainability perspective.

Results: Each stage, from the patient's means of transport to the hospital to the physician's diagnostic and therapeutic decisions, contribute to CO₂ and waste production. Strategies to contain the environmental impact are feasible. Some are easy to implement, such as ensuring the appropriateness of the diagnostic and therapeutic pathway for patients; others need to be implemented in synergy with healthcare providers' policies and pharmaceutical companies.

Conclusions: With an inevitable increase in the number of patient visits, endoscopies, laboratory testing, and long-term therapeutic strategies for IBD, the clinical community should be aware of environmental concerns and investigate possible strategies to reduce the environmental impact of IBD care.

Background: Muscle cramps are common in patients with cirrhosis. Despite their prevalence and impact on health-related quality of life, there are no widely used clinical practice guidelines for management of muscle cramps in cirrhosis. The aim of this review was to critically evaluate current evidence regarding treatment of muscle cramps in cirrhosis.

Methods: A systematic review using PubMed, MEDLINE (Ovid), Embase, and Scopus databases was performed on 30 June by two independent reviewers to identify randomised controlled trials (RCTs) reporting interventions for muscle cramps in cirrhotic patients.

Results: Twelve RCTs evaluating 13 distinct interventions were identified. Baclofen, methocarbamol, orphenadrine, and taurine supplementation reduced cramp frequency, severity, and duration when compared to placebo. Human albumin, pregabalin, and quinidine reduced cramp frequency compared to placebo. Pickle juice reduced cramp severity compared to placebo. BCAA supplementation and calcium carbonate were found to reduce cramp frequency compared to baseline. Stretching demonstrated a signal towards reducing cramp severity and frequency, and meditation had a signal towards reducing severity only when compared to baseline. Electro-acupuncture was the only intervention which demonstrated no therapeutic effect. Pregabalin was the only agent associated with significant side effects that limited its use.

Conclusion: Methocarbamol, orphenadrine, and taurine supplementation were found in placebo-controlled RCTs to be effective in reducing cramp frequency, severity, and duration in cirrhotic patients. All other interventions reported aside from electro-acupuncture demonstrated a positive impact on cramps. High-quality RCTs are needed to further investigate the use of these treatments in terms of comparative efficacy and safety.

Background: High placebo responses have limited drug development in eosinophilic oesophagitis. The optimal configuration of trial outcomes is uncertain.

Aims: To inform more efficient future trial designs, to characterise clinical, endoscopic and histologic placebo responses in eosinophilic oesophagitis randomised controlled trials (RCTs).

Methods: We updated a Cochrane systematic review and meta-analysis, searching multiple databases to January 1, 2024, to identify placebo-controlled RCTs evaluating medical therapies for patients with eosinophilic oesophagitis. The primary outcome was the pooled proportion of study-defined clinical, endoscopic and histologic responders and remitters randomised to placebo, using an intention-to-treat approach and random-effects model. Sources of heterogeneity were explored using meta-regression.

Results: We included 25 RCTs. The pooled proportion of clinical response was 41.0% [95% CI: 29.7%-52.8%] with substantial heterogeneity (I² = 74.9%). On meta-regression, older age and a higher probability of being randomised to placebo reduced the likelihood of clinical response to placebo. The pooled proportion of histologic remission defined as a peak eosinophil count [PEC] ≤ 6 eosinophils per high power field [HPF] or ≤ 1 eosinophil/HPF was 4.3% [95% CI: 2.6%-6.2%] (I² = 23.6%) and 1.3% [95% CI: 0.5%-2.5%] (I² = 0%), respectively. The standardised mean difference in the Eosinophilic Oesophagitis Endoscopic Reference Score to placebo was -0.25 [95% CI: -0.41, -0.10].

Conclusions: Over 40% of patients in eosinophilic oesophagitis trials respond clinically to placebo, and this is associated with trial design factors such as randomisation ratio and trial population. Objective endoscopic and histologic measures are associated with very low placebo responses.