A RANDOMIZED PARALLEL-GROUP STUDY OF SELF-ADMINISTERED, DIGITAL GUT-DIRECTED HYPNOTHERAPY VS. MUSCLE RELAXATION FOR IRRITABLE BOWEL SYNDROME

Background: Crohn’s disease (CD) is a chronic inflammatory intestinal disorder, for which the majority of patients need to undergo surgery. Following ileocolonic resection, most patients experience recurrent CD in the neoterminal ileum. Endoscopic lesions usually precede symptoms and predict the severity of the disease course. No treatments have been approved for recurrence-prevention CD. REPREVIO is a prospective placebo-controlled randomized trial investigating the preventive effect of vedolizumab, an anti-integrin antibody, on recurrence of CD.
Methods: Following ileocolonic resection, patients were randomized to treatment with intravenous vedolizumab (300 mg at week 0,8,16 and 24) or PLC (1:1) at 12 sites in the Netherlands, France, Italy and Spain. Patients and investigators were blinded to treatment assignment that was initiated within 4 weeks of ileocolonic resection with anastomosis. Twenty-six weeks after randomization patients underwent ileocolonoscopy for assessment of recurrent CD lesions. Video recordings were centrally scored using the modified Rutgeerts’ score (i0-i4) by 2 readers with adjudication in case of disagreement. The primary endpoint was endoscopic recurrence (ER) of Crohn’s disease according to Rutgeerts classification categories (non-parametric analysis of distributions between groups); secondary endpoints were the proportion of patients with ER >i2a, endoscopic remission (i0) and clinical recurrence (CDAI increase >70 points between baseline and week 24). Data analysis was based on intent-to-treat with patients dropping out or not having final endoscopy counted as failure (i4). Adverse events were recorded.
Results: Of 95 pts screened, 80 were randomized. Seventy-six patients reached week 26 (2 drop-outs for withdrawal of consent, 1 for perforation and 1 for cancer). Baseline patient characteristics were comparable as shown in table 1. Using a non-parametric analysis, patients in the treatment group had a 77.8% (95% CI 66.4 to 86.29%) chance of having a better Rutgeerts’ score than control patients (p <0.0001). Based upon the dichotomized analysis of high risk recurrence versus low risk recurrence (i0-2A versus i2B-i4), 77% of patients who received VDZ had i0-2A versus 38% for PLC, yielding an absolute difference of 39% in favor of VDZ (p=0.0004)(figure 1). Endoscopic remission (i0) was observed in 18/43 pts for VDZ (42%) versus 1/37 pt for PLC (3%)(p<0.001). Clinical recurrence (CDAI increase >70 pts between baseline and week 24) occurred in 9 pts on VDZ and 8 pts on PLC. No new safety signals were observed.
Conclusion: Treatment with VDZ started immediately after ileocolonic resection is highly effective for the prevention of postoperative recurrence of CD.

Background: There has been increasing interest in artificial intelligence in gastroenterology. To reduce miss rate during colonoscopy, there has been significant exploration in computer aided detection (CADe) devices. In this study, we evaluate the use of CADe in colonoscopy in community based, non-academic practices.
Methods: Between September 28, 2020 and September 24, 2021, a randomized controlled trial (AI-SEE) was performed evaluating the impact of CADe on polyp detection in 4 private practice endoscopy centers in the USA. Patients were block randomized to undergoing colonoscopy with or without CADe. Primary outcomes measured were adenomas per colonoscopy (APC) and adenomas per extraction (APE; the percentage of polyps removed that are adenomas). Secondary endpoints included serrated polyps per colonoscopy, non-adenomatous, non-serrated polyps per colonoscopy, adenoma and serrated polyp detection rate, and procedural time.
Results: A total of 769 patients were enrolled (387 with CADe), with similar patient demographics between the two groups. There was no significant difference in adenomas per colonoscopy in the CADe and non-CADe groups (0.73 vs 0.67, p=0.496). While use of CADe did not improve identification of serrated polyps per colonoscopy (0.08 vs 0.08, p=0.965), use of CADe increased identification of non-adenomatous, non-serrated polyps per colonoscopy (0.90 vs 0.51, p<0.0001), resulting in a lower APE in the CADe group (Table 1). Adenoma detection rate (35.9 vs 37.2%, p=0.774) and serrated polyp detection rate (6.5 vs 6.3%, p=1.000) were similar in the CADe and non-CADe group (Table 2). Mean withdrawal time was longer in the CAD compared to non-CADe group (11.7 vs 10.7 minutes, p=0.003). However, when no polyps were identified, there was similar mean withdrawal time (9.1 vs 8.8 minutes, p=0.288). There were no adverse events.
Conclusions:
To our knowledge, this is the first prospective multicenter study to assess the clinical impact of real-time CADe in primarily non-academic centers. In contrast to prior studies, use of CADe did not result in a statistically significant difference in the number of adenomas detected. Additional studies are needed to better understand why some endoscopists derive substantial benefits from CADe and others do not.

There are no approved treatments for eosinophilic esophagitis (EoE) in children <12 years. Dupilumab (DPL), a fully human mAb, blocks the shared receptor component for interleukin (IL)-4/IL-13, key and central drivers of type 2 inflammation in EoE. In the phase 3 LIBERTY-EoE-TREET study, DPL demonstrated improvements in histologic, symptomatic, and endoscopic outcomes and was well tolerated in adolescents and adults with EoE. Part A of the 3-part phase 3 EoE KIDS trial (NCT04394351) evaluated efficacy, safety, and tolerability of DPL vs placebo (PBO) in pediatric patients aged 1–11 years with active EoE up to 16 weeks (wks).
102 participants were randomized 1:1:1 to receive subcutaneous DPL at a weight-tiered, higher- (n=37), or lower-dose (n=31), or matching PBO (n=34) for 16 wks. Key inclusion criteria: documented diagnosis of EoE unresponsive to ≥8-wk proton pump inhibitor (PPI) and baseline esophageal intraepithelial eosinophil (eos) count ≥15eos/high-power field (hpf) in ≥2 of 3 regions. Key exclusion criteria: body weight <5kg or ≥60kg at screening; eosinophilic gastroenteritis; non-EoE causes of esophageal eosinophilia.
At Wk 16, 68% and 58% of children on higher- and lower-dose DPL achieved primary endpoint of peak esophageal intraepithelial eos count (PEC) ≤6eos/hpf, vs 3% on PBO (both P<0.0001). At Wk 16, children on higher-dose DPL experienced the following changes from baseline: –86% in PEC vs +21% for PBO (P<0.0001); –0.88 and –0.84 in EoE Histologic Scoring System (HSS) grade and stage scores, respectively, vs +0.02 and +0.05 for PBO (both P<0.0001); –3.5 in EoE Endoscopic Reference Score (EREFS) vs +0.3 for PBO (P <0.0001); numeric improvement in caregiver-reported % days experiencing ≥1 EoE signs; +3.09-percentile in body weight for age vs +0.29 for PBO. Changes in histologic, anatomic and cellular outcomes were comparable in the lower-dose group (all nominally significant vs PBO). Overall rates of adverse events (AEs) were 79% for DPL and 91% for PBO. AEs more commonly observed with DPL vs PBO included COVID-19, rash, and headache.
This phase 3 trial assessing DPL vs PBO in children aged 1–11 years with active EoE met its primary endpoint of histologic disease remission at 16 wks with both higher- and lower-doses. DPL higher-dose also demonstrated significant and clinically meaningful changes in additional histologic and endoscopic outcomes and improvements in clinical symptoms and weight.

Background: Gut-directed hypnotherapy (GDH) is effective for treating irritable bowel syndrome (IBS), but access issues limit its widespread use. Preliminary studies also suggest that muscle relaxation might benefit patients with IBS.

Aim: To compare the safety and efficacy of a self-administered, digital GDH treatment program with that of digital muscle relaxation (MR) in adults with IBS.

Methods: A multicenter, randomized, double-blind, controlled study enrolling patients from 26 centers in the USA from December 2019 to October 2020. Eligibility criteria included patients aged 18 to 70 years meeting the Rome IV criteria for IBS who reported an Average Worst Daily Pain Severity score of ≥3 on an 11-point scale over a 4-week run-in period. Patients were randomized to 12 weeks of treatment with digital GDH via the North Carolina protocol or digital muscle relaxation (MR) control via a mobile app. The primary endpoint was abdominal pain, defined as ≥30% reduction from baseline in average daily abdominal pain intensity 4 weeks post-treatment. Key secondary outcomes included mean change from baseline abdominal pain, stool consistency and frequency.

Results: Of 378 randomized patients, 362 were treated and included in the efficacy analysis. 30.4% of patients in the GDH group met the primary endpoint compared with 27.1% of those who received MR (P=0.5352). More patients treated with GDH than MR were abdominal pain responders during the last 4 weeks of treatment (30.9% vs 21.5%, P=0.0232) and over the entire treatment period (29.3% vs 18.8%, P=0.0254). More patients treated with GDH met the primary endpoint but statistical significance was not met (P=0.532) (Figure 1A). However, significantly more GDH-treated patients were abdominal pain responders during the last 4 weeks of treatment and the entire treatment period compared with those receiving MR (Figure 1B). During weeks 13 through 16 posttreatment, 44.9% and 41.3% of patients in the GDH and MR groups were stool consistency responders (P=0.51) (Figure 2). No patients experienced serious adverse events.

Conclusion: This large, randomized trial is the first study to assess the use of an all-digital program for delivering GDH in patients with IBS. The benefits observed with this digital therapeutic were consistent with those described with in-person individual and group GDH in patients with IBS. Similar studies have shown symptom reduction with GDH vs. control interventions considered active treatments, including biofeedback, therapist or gastroenterologist led education, and low FODMAP diet. Our findings provide support for the digital delivery of GDH via the North Carolina protocol. Treatment with a digital GDH program led to robust improvements in abdominal pain and stool symptoms in patients with IBS, supporting a role for this intervention as part of integrated care for IBS.