A double-blind randomized, multicenter, placebo-controlled study of itopride in functional dyspepsia postprandial distress syndrome.

BACKGROUND: Itopride, a mixed D2 antagonist and cholinesterase inhibitor, has prokinetic effects on gastric motility. The Leuven Postprandial Distress Scale is a validated patient-reported outcome instrument for functional dyspepsia (FD) postprandial distress syndrome (PDS). We aimed to use the LPDS to assess treatment outcome in PDS and PDS/EPS (epigastric pain syndrome). METHODS: Patients with PDS, with or without non-predominant EPS symptoms, were enrolled in an 8-week double-blind placebo-controlled multi-center trial with itopride (100 mg t.i.d.). Patients completed LPDS diaries and questionnaires to assess treatment response. Mann-Whitney test and mixed models were used. RESULTS: One hundred patients (79% females, 39.1 ± 1.5 yo) were included. No significant difference was observed between treatment arms (p = 0.6). Compared to baseline, itopride treatment significantly improved the LPDS score (p = 0.001) and all individual symptoms (p < 0.0001). In the placebo arm, this was only the case for belching and epigastric pain (p < 0.05). In an exploratory analysis, outcomes in "pure" PDS (n = 45) and overlapping PDS/EPS (n = 55) patients were assessed and showed that the latter subgroup has the largest benefit with itopride compared to placebo (p = 0.03). CONCLUSION: Using the LPDS score in a pilot controlled trial in FD, itopride shows no therapeutic benefit over placebo after 8 weeks of treatment. In an exploratory post hoc analysis, itopride but not placebo was associated with improvement of symptoms compared to baseline, and this was most prominent in patients with overlapping PDS/EPS. The efficacy of itopride in this subgroup needs to be evaluated in a large study using the same outcome measure. (clinialtrials.org ref.: NCT04647955).

Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients.

BACKGROUND AND AIMS: Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1 year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a large cohort of adalimumab treated Crohn's patients. METHODS: All consecutive patients treated with open label adalimumab for active Crohn's disease from the participating centres were included in this cohort study. A detailed retrospective chart review was performed to look for possible factors predicting outcome. RESULTS: Eighty four percent of 720 patients had a primary response and were followed up for a median of 14 months. Thirty four percent needed escalation after a median of 7 months (0-55 months). Multivariate predictors for dose escalation were the following: prior anti-TNF use (p<0.0001), no concomitant azathioprine or <3 m (p<0.02) and abnormal CRP at start (p<0.05). Dose escalation re-induced response for at least 6 months in 67%. Only abnormal CRP at start correlated with failure of dose escalation (p=0.02). Dose de-escalation was attempted in 54% and was successful in 63%. After a median follow-up of 14 m adalimumab was discontinued in 29% of patients. CONCLUSION: In this study real life nationwide cohort of Crohn's patients treated with adalimumab dose escalation was needed in 34% and was successful in 67%. Dose de-escalation was attempted in 54% and was successful in 63%. Overall 71% of patients maintained long term response on adalimumab.