Michael A. Kamm

In the version of this article initially published, the surname of Emily Crossette was misspelled (as Crossett), while an additional affiliation for Varun Aggarwala (Reliance Foundation Institution of Education and Research, Jio Institute, Navi Mumbai, India) was missing; the changes have been made in the HTML and PDF versions of the article.

Background: The enteric microbiota drives inflammation in Crohn's disease. Yet, there are no placebo controlled trials evaluating the efficacy and safety of faecal microbiota transplantation (FMT) in inducing and maintaining remission in patients with active Crohn's disease. The Microbial Restoration (MIRO) study aims to establish this evidence. Methods: At two specialist inflammatory bowel disease centres, 120 enrolled patients will have a 3-week period of diet optimisation (removal of ultra-processed foods) together with a 7-day course of antibiotics (to facilitate subsequent FMT engraftment). Patients will then be stratified to upper gut (for disease proximal to the splenic flexure) or lower gut (distal to the splenic flexure) disease. Patients will then be randomised in a 2:1 ratio to receive anaerobically prepared stool or placebo for 8 weeks either by gastroscopy, or colonoscopy and enemas. Clinical response at 8 weeks (Crohn's Disease Activity Index (CDAI) reduction ≥100 points or to <150 points) is the primary outcome measure. Non-responders to placebo and partial responders to FMT (CDAI decrease <100 but >70) receive FMT for weeks 8-16.Patients achieving clinical response from FMT after 8 or 16 weeks will be randomised in a 1:1 ratio to either a 44-week maintenance phase of FMT or placebo. Patients will receive FMT from one donor throughout the study.The MIRO study will establish whether FMT is an effective and safe therapy to induce and maintain remission in patients with active Crohn's disease. Background: Ethical approval has been received by the St Vincent's Hospital Melbourne Human Research Ethics Committee (HREC-A 084/21). The results will be disseminated in peer-reviewed journals and presented at international conferences. Background: ClinicalTrials.gov: NCT04970446; Registered on 20 July 2021.

Objective: Exclusive Enteral Nutrition (EEN) and the Crohn's Disease Exclusion Diet (CDED) have been shown to induce remission in Crohn's disease. Low-sulphur, plant-based diets are being explored for ulcerative colitis, and wholefood, low-additive approaches are emerging as significant. Although Inflammatory Bowel Disease (IBD) patients modify their diet, evidence for tolerability and benefit outside clinical trials is limited. The DELECTABLE program aimed to assess satisfaction, adherence, and efficacy of dietary therapies as part of IBD care. Methods: In this dietitian-led, open-label, prospective study, patients with Crohn's disease were offered the CDED or a whole-food, additive-free diet (WFD), and patients with ulcerative colitis were offered a low-sulphur, plant-based diet (UCD) or WFD. Primary outcomes were 12-week diet satisfaction (modified DSAT-28) and diet adherence, including food additive intake. Secondary outcomes were quality of life (QoL) (IBDQ-9), disease activity (CDAI for Crohn's disease, partial Mayo score for ulcerative colitis), and biochemical markers (CRP, faecal calprotectin). Analyses were conducted within, rather than between, diet arms due to the non-random nature of the study. Diet adherence and disease activity change across time points (baseline, week 6, week 12) were assessed using repeated measures ANOVA or Friedman's test, with pairwise paired t-test or Wilcoxon Signed-Rank test. Diet satisfaction and quality of life changes across time (baseline/week 1, week 12) were assessed using a paired t-test or Wilcoxon Signed-Rank test. Results: Of 165 referrals, 76 patients enrolled, with 64 completing the 12-week program (CDED: n = 15, WFD: n = 42, UCD: n = 7). Diet satisfaction was initially high and remained stable over time on CDED (p = 0.212) and improved on WFD (p = 0.03). Patient- and dietitian-rated adherence was high at baseline and did not significantly decrease on any diet arm (p > 0.349). Food additive intake decreased on WFD (p = 0.009). QoL improved on CDED and WFD (p < 0.001). CRP, calprotectin, and CDAI were reduced on CDED (p < 0.045), and CDAI and partial Mayo were reduced on WFD (p < 0.027). Conclusions: Well-balanced therapeutic diets are feasible and well-accepted by patients with IBD, with a promising impact on disease activity.

Background: Transmural healing is emerging as a key treatment target in Crohn's disease. This study aimed to determine the role of magnetic resonance imaging (MRI) and intestinal ultrasound (IUS) in the assessment of the radiologic response of Crohn's disease strictures to treatment. Methods: The STRIDENT (Stricture Definition and Treatment) study was a randomized controlled trial of (2:1) intensive high-dose adalimumab combined with a thiopurine vs standard dose monotherapy adalimumab in patients with stricturing Crohn's disease. Clinical response was defined as a reduction in the Obstructive Symptom Score at 12 months. Intestinal ultrasound was performed at baseline, 4, 8, and 12 months and MRI at baseline and 12 months. This study examines secondary outcomes of stricture resolution and changes in stricture morphology with treatment. Results: Of 77 patients, 52 were in the intensive treatment group and 25 in the standard therapy group. Clinical response was achieved in 56 of 77 patients (73%). Complete stricture resolution occurred in 17 patients on IUS (29%) and 16 patients on MRI (22%). Stricture improvement occurred in 23 of 59 patients on IUS (39%) and 24 of 72 patients on MRI (33%). Bowel wall thickness improved at 12 months on both IUS (P < .0001) and MRI (P < .001) and was significantly lower in clinical responders (IUS P = .003) and those with fecal calprotectin < 100 µg/g (IUS P < .001; MRI P = .001). Conclusions: Radiologic severity of Crohn's disease strictures can improve with drug treatment, with complete stricture resolution observed in some. Intestinal ultrasound and MRI are effective modalities for monitoring the treatment response in patients with stricturing Crohn's disease (STRIDENT Drug Therapy Study: NCT03220841).

Objective: Crohn's perianal fistula healing rates remain low. We evaluated the efficacy of a protocolized multidisciplinary treatment strategy optimizing care in adults with Crohn's perianal fistulas. Methods: A new treatment strategy was established at a single tertiary center. The strategy comprised 3 dynamic stages of care directed toward achieving and maintaining fistula healing. Stage A, active disease, focused on early commencement and proactive escalation of biologic therapies and structured surgical reviews ensuring adequate fistula drainage and conditioning. Stage B, optimized disease with a seton in situ, focused on consideration for seton removal and appropriateness of definitive surgical closure and/or ablative techniques. Stage C, healed disease, focused on proactive care maintenance. Sixty patients were sequentially enrolled and prospectively followed for ≥12 months. Endpoints included clinical healing and radiologic remission in those with clinically active fistulas, and relapse in those with healed fistulas. Results: At baseline, 52% (n = 31) and 48% (n = 29) had clinically active and healed fistulas, respectively. For patients with clinically active fistulas, 71% achieved clinical healing after 22 months, with estimated healing rates of 39% and 84% at 1 and 2 years, respectively. Radiologic remission was achieved in 25%, significantly higher than baseline inclusion rates of 6%. For patients with healed fistulas, 7% experienced clinical relapse after 23 months, with no significant change in radiologic remission, 80% versus 86% at baseline. Conclusions: A protocolized treatment strategy proactively optimizing care resulted in high rates of clinical healing and improved radiologic remission of Crohn's perianal fistulas. Controlled-matched studies are needed.

A Phase III, Randomised, Double-Blind, Dose-Response, Stratified, Placebo-Controlled Study Evaluating the Safety and Efficacy of SPD476 Versus Placebo Over 104 Weeks in the Prevention of Recurrence of Diverticulitis.