BACKGROUND: A treat-to-target strategy for inflammatory bowel disease (IBD) recommends iterative treatment adjustments to achieve clinical and endoscopic remission. In asymptomatic patients with ongoing endoscopic activity, the risk/benefit balance of this approach is unclear, particularly with prior exposure to advanced therapies. METHODS: Using the RAND/University of California Los Angeles Appropriateness Method, 9 IBD specialists rated appropriateness of changing therapy in 126 scenarios of asymptomatic patients with ulcerative colitis and Crohn's disease and active endoscopic disease. Disease extent and behavior, prior treatment, prior complications, and recent disease progression were considered, as were factors that might influence decision-making, including age and pregnancy. Ratings were collected through anonymous survey, discussed at an in-person meeting, and finalized in a second anonymous survey. RESULTS: Panelists rated change in therapy as appropriate (i.e., expected benefit sufficiently outweighs potential harms from continuing therapy) in 96/126 scenarios, generally in patients with progressive, complicated, and/or extensive disease, while changing therapy was rated uncertain in 27 scenarios of mild and/or stable disease. Changing therapy was rated inappropriate in ulcerative colitis patients with mild and stable disease previously exposed to ≥3 therapies or with improved endoscopic activity, and in Crohn's disease patients with only scattered aphthous ulcers. The validated threshold for disagreement was not crossed for any scenario. Patient age older than 65 years and a plan for pregnancy in the next year might influence decision-making in some settings. DISCUSSION: Appropriateness ratings can help guide clinical decision-making about changing therapy to achieve endoscopic remission in asymptomatic patients with IBD until data from ongoing randomized studies are available.

Abstract Background The treat-to-target strategy for inflammatory bowel disease (IBD) recommends optimising or changing therapy in patients who have not achieved clinical remission and endoscopic healing. In asymptomatic patients, the potential benefit of changing therapy to achieve endoscopic healing is less clear, particularly since <40% typically achieve endoscopic healing with current therapy. We sought to define appropriateness of changing therapy in asymptomatic IBD patients with active endoscopic inflammation. Methods Using the RAND/UCLA Appropriateness Method, a panel of 9 IBD specialists considered appropriateness of changing therapy in 16 scenarios of patients with ulcerative colitis (UC) and 96 scenarios of Crohn’s disease (CD), rated on a 9-point Likert scale as inappropriate (1-3), uncertain (4-6), or appropriate (7-9). Patients in all scenarios were asymptomatic with active endoscopic disease; variables included disease extent, behaviour, prior treatment, recent disease progression, and prior disease complications. Current therapy was assumed to be optimised, so the only options were changing therapy or continuing current therapy. An additional 14 scenarios explored patient factors that might influence treatment decision-making. Ratings were collected via online anonymous survey, discussed at an in-person meeting, then finalised in a second anonymous survey using a modified Delphi approach. Disagreement was assessed using a validated index. Results Panelists rated it appropriate to change therapy (i.e., expected benefit sufficiently exceeds expected negative consequences) in 96/126 scenarios, generally those with progressive, complicated, and/or extensive disease; 27 scenarios of mild and/or stable disease were rated uncertain, particularly with prior exposure to ≥3 drug classes. Changing therapy in asymptomatic patients was rated inappropriate in 3 scenarios: in Mayo 1 UC previously treated with ≥3 therapy classes with no endoscopic progression in the last year; in any patient who showed endoscopic improvement over the last year; and in any patient with CD who had only scattered aphthous ulcers. Patient age >65 years influenced a decision to change therapy specifically for anti-TNFs and JAK inhibitors; the possibility of pregnancy also influenced decision-making. Despite variability in ratings, the threshold for disagreement was not crossed for any scenario. Conclusion Our panel of IBD specialists rated appropriateness of changing therapy to achieve endoscopic healing in asymptomatic patients with UC and CD in a variety of scenarios. Our findings can be used to help guide clinical decision-making in this population until data from ongoing randomised studies are available (NCT05230173).

Abstract Background The COVID-19 pandemic caused by SARS-CoV-2 has reduced access to endoscopy and imaging. Safe alternatives, available at the bedside, are needed for accurate, non-invasive strategies to evaluate disease activity. The aim of this study is to establish the impact of clinic-based bedside intestinal ultrasound (IUS) on decision making, reduction in reliance on endoscopy and short-term healthcare utilization. Methods We conducted a prospective observational evaluation during the COVID-19 pandemic, of the impact of a regional comprehensive care pathway to manage IBD patients consecutively recruited with acute symptoms, or suspected new diagnosis of IBD. Clinic-based access to sigmoidoscopy and bedside intestinal ultrasound were evaluated, used to direct clinical care and avoid hospitalization or hospital-based endoscopy. Results A total of 72 patients were seen between March 15 and June 30, 2020. Of these, 57% (41/72) were female, 64% had Crohn’s disease (46/72) with 14% (10/72) presenting with symptoms requiring investigation, of which 5 new cases of IBD were identified (50%). Immediate access to ultrasound and sigmoidoscopy led to meaningful changes in management in 80.5% (58/72) of patients. Active inflammation was detected by IUS alone (72.5%, 29/40) or in combination with in-clinic sigmoidoscopy (78%, 18/23) or sigmoidoscopy alone (78% 7/9). Six patients were referred to colorectal surgery for urgent surgical intervention including two patients admitted directly. Conclusion Implementation of IUS as part of a clinical care pathway during the COVID-19 pandemic is a useful strategy to enhance care delivery and improve clinical decisions, while sparing other important acute care resources.

Background and Aims The treatment of chronic pouchitis remains a challenge due to the paucity of high-quality studies. We aimed to provide guidance for clinicians on the appropriateness of medical and surgical treatments in chronic pouchitis. Methods Appropriateness of medical and surgical treatments in patients with chronic pouchitis was considered in 16 scenarios incorporating presence/absence of four variables: pouchitis symptoms, response to antibiotics, significant prepouch ileitis, and Crohn's disease (CD)-like complications (i.e., stricture or fistula). Appropriateness of permanent ileostomy in patients refractory to medical treatments was considered in eight additional scenarios. Using the RAND/UCLA appropriateness method, international IBD expert panelists rated appropriateness of treatments in each scenario on a 1-9 scale. Results Chronic antibiotic therapy was rated appropriate only in asymptomatic antibiotic-dependent patients with no CD-like complications and inappropriate in all other scenarios. Ileal-release budesonide was rated appropriate in 6/16 scenarios including patients with significant prepouch ileitis but no CD-like complications. Probiotics were considered either inappropriate (14/16) or uncertain (2/16). Biologic therapy was considered appropriate in most scenarios (14/16) and uncertain in situations where significant prepouch ileitis or CD-like complications were absent (2/16). In patients who are refractory to all medications, permanent ileostomy was considered appropriate in all scenarios (7/8) except in asymptomatic patients with no CD-like complications. Conclusions In the presence of significant prepouch ileitis or CD-like complications, chronic antibiotics and probiotics are inappropriate. Biologics are appropriate in all patients except in asymptomatic patients with no evidence of complications. Permanent ileostomy is appropriate in most medically refractory patients.

INTRODUCTION: The optimal treatment of chronic inflammatory pouch disorders remains a challenge due to the paucity of high-quality studies. We aimed to provide guidance for clinicians on the appropriateness of medical and surgical treatments in patients with these disorders. METHODS: The appropriateness of medical and surgical treatments in patients with pouchitis was considered in 16 clinical scenarios incorporating pouchitis symptoms, antibiotic response, prepouch ileitis (PI) (extending >10 cm proximal to pouch inlet) and Crohn's disease (CD)-like complications. Appropriateness of permanent ileostomy was considered in 8 additional scenarios. Using the RAND/UCLA modified Delphi method, 13 international inflammatory bowel diseases experts rated appropriateness of treatments on a 1–9 scale (1–3 inappropriate, 4–6 uncertain, 7–9 appropriate) via a web-based survey, then met to discuss and re-rate scenarios. Disagreement was assessed using a validated index; scenarios with disagreement were rated as uncertain. RESULTS: Chronic antibiotic therapy was rated appropriate only in asymptomatic antibiotic-dependent patients with no CD-like complications and was otherwise inappropriate (Table 1). Ileal-release budesonide was rated appropriate in 6/16 (38%) scenarios including patients with extensive PI but no CD-like complications. Its use was considered inappropriate (5/8) or uncertain (3/8) in the presence of CD-like complications. Probiotics were considered inappropriate in 14/16 (88%) and uncertain in 2/16 (12%) scenarios. Biologic therapy was considered appropriate in 14/16 (88%) scenarios and uncertain in the absence of extensive PI or CD-like complications (12%). Permanent ileostomy was considered appropriate in 3/16 (19%) scenarios including symptomatic patients with extensive PPI and CD-like complications (Table 2). In patients refractory to all medical treatments, permanent ileostomy was considered appropriate in all scenarios except in asymptomatic patients with no CD-like complications. CONCLUSION: In the presence of extensive PI or CD-like complications, chronic antibiotics and probiotics are inappropriate. Ileal-release budesonide is appropriate in patients who have chronic pouchitis with extensive PI but no CD-like complications. Biologic use is appropriate in patients with chronic pouchitis except in asymptomatic patients with no evidence of complications. Permanent ileostomy is appropriate in most patients who have failed all medical treatments.Table 1.: Appropriateness of medical and surgical treatments in patients with chronic pouch inflammationTable 2.: Appropriateness of a permanent ileostomy in patients with chronic pouch inflammation who have failed antibiotics, ileal release budesonide, probiotics and biologics

The use of complementary and alternative medications (CAM), products, and therapies not considered to be part of conventional medicine is common among patients with inflammatory bowel disease (IBD). Patients often turn to these therapies as they are considered natural and safe, with significant benefit reported beyond disease control. There is emerging evidence that some of these therapies may have anti-inflammatory activity; however, robust evidence for their efficacy in modulating disease activity is currently lacking. Patients often avoid discussing the use of CAM with their physicians, which may lead to drug interactions and/or reduced adherence with conventional therapy. It is important for physicians to be aware of the commonly used CAM and current evidence behind these therapies in order to better counsel their patients about their use in the management of IBD. This narrative review provides an overview of the evidence of the more commonly used CAM in patients with IBD.

INTRODUCTION: Treatment options for patients with moderate-severe ulcerative colitis (UC) are increasing. The appropriateness of their use in mild-moderate UC is less clear, as is the role of surgical intervention. Our aim was to define the appropriateness of therapeutic options in a range of clinical scenarios in mild-moderate UC METHODS: We applied the RAND/UCLA Appropriateness Method to rate appropriateness of treatment choices in patients with mild-moderate UC; severe disease (likely to need hospitalization or surgery within 2 weeks) was excluded. A literature review was presented to the BRIDGe group, a panel of 13 IBD specialists, as well as 1 external IBD expert and 2 IBD surgical experts. 12 chapters were constructed including failed 5-ASA, steroid or thiopurine therapy, and primary/secondary non-response to biologics or tofacitinib. Scenarios were also divided by disease extent (proctitis vs more extensive) and activity (mild vs moderate) creating 260 scenarios in all. Panellists used a modified Delphi method to anonymously rate the appropriateness of a therapy on a 1-9 scale (1-3 not appropriate, 4-6 uncertain, 7-9 appropriate). Disagreement was assessed using a validated index (DI) and was defined as a DI > 1. The panellists then convened in person to discuss areas of disagreement, followed by a second round of rating. Scenarios rated a median of 7 or higher were deemed appropriate and those rated 3 or lower were deemed inappropriate. Scenarios rated 4-6 were considered uncertain, as were any with a DI > 1 RESULTS: Appropriateness was agreed in 131 and inappropriateness in 47 scenarios. Greatest disagreement was around the use of thiopurines, but no scenario had a DI > 1. There were 82 scenarios were rated uncertain. Biologics and tofacitinib were more likely to be rated appropriate for treatment resistance and greater disease activity; disease extent less likely to influence decision making. Surgery was felt to be appropriate in 8 scenarios, generally in more extensive and active disease that had failed to respond to medical therapy. Surgery was felt to be inappropriate in 16 scenarios and was uncertain in 24 CONCLUSION: Although there was little disagreement amongst an expert panel of IBD physicians and surgeons, there remained uncertainty about the use of medical and surgical therapy in nearly one third of situations in patients with mild-moderate UC. These results could be used to guide the design of clinical trials for these patient groups in order to guide best practice.

BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD. METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score >= 7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting. RESULTS: The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios. CONCLUSION: Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.

Deep remission is a treatment goal for patients with Crohn's disease, after which de-escalation of medical therapy may be considered. However, applicability of available study data to real-world clinical practice can be challenging. We evaluated the appropriateness of de-escalating immunomodulator or anti-tumour necrosis factor therapy in Crohn's disease patients in deep remission. A literature review was presented to a panel of international experts in Crohn's disease. Appropriateness of de-escalation in patients in deep remission for at least 6 months was considered in 240 scenarios across five chapters. Using a modified Delphi method, panel members rated appropriateness of de-escalation in each scenario via a web-based survey, then met to discuss the topic and re-rated the scenarios. Scenarios with disagreement were rated as uncertain. De-escalation was rated appropriate in only 32/240 scenarios (13.3%), including 19 of elderly patients on combination therapy. De-escalation was rated inappropriate in 59/240 scenarios (24.6%), including 22 of patients on monotherapy and 35 of patients on combination therapy stopping anti-tumour necrosis factor therapy. More than 60% of scenarios (149/240) were rated uncertain, including 42 of patients with complicated disease on combination therapy stopping or dose-reducing immunomodulators. Discontinuing anti-tumour necrosis factor or immunomodulator therapy was largely not recommended, except in scenarios of elderly patients with uncomplicated CD or those on combination therapy stopping or dose-reducing immunomodulators. As nearly two-thirds of scenarios were rated uncertain, additional data are needed to better inform clinicians regarding the benefits and risks of de-escalating medical therapy in Crohn's disease.

Ultrasound (US) is safe and accurate for detecting activity and therapeutic response in Crohn’s disease (CD). Early objective assessment may better guide treatment in a treat to target paradigm. The aim of this study is to evaluate 12-week US response to adalimumab (ADA) induction, as a predictor of US, serologic and endoscopic response at 6 months. Patients with known CD were prospectively recruited from January 1, 2011 to December 31, 2014. Patients with active CD had induction and maintenance therapy with ADA with US and C-reactive protein (CRP) levels measured pre-treatment, at 12 weeks and 6 months. Patients underwent ileocolonoscopy (IC) at baseline. A subset had repeat IC at 6 months. The Simple Ultrasound Score (SUS) was calculated (bowel wall thickness and hyperaemia) at each interval and a Simple Endoscopic Score (SES)/Rutgeert’s score for IC when available. Response at 12 weeks was defined by a reduction in SUS or length of disease. Differences between variables at baseline and 6 months were compared using paired sample t test. Features for non-response including presence of strictures or penetrating complications were recorded at baseline. Forty-four patients were included: 64% (28 of 44) females, 36% (16 of 44) male, with mean age of 42 years. Disease distribution was ileal 38% (17 of 44), 55% (24 of 44) ileocolonic and 7% (3 of 44) limited to the colon. All patients exhibited activity on US at baseline, with a mean SUS of 3.14 (out of 4.63). SES was completed for 22 of 44 patients (50%), mean 6.82, Rutgeert’s score was completed for 11 of 44 patients (25%), mean 3.27, while 18% (8 of 44) were not amenable to endoscopic scoring and 7% (3 of 44) had no baseline IC. The median baseline CRP was 5.7 mg/l. At 12 weeks, 70% (31 of 44) improved while 30% (13 of 44) had no change or worsened. Responders were evaluated at 6 months for response compared with baseline: SUS and SES were significantly improved, SUS was 3.45 at baseline and 1.84 at 6 months (p < 0.001) and SES was 6.77 at baseline and 2.50 at 6 months (p = 0.002). Change in CRP was significant (p = 0.044); but the change in Rutgeert’s score was not (p = 0.178). No significant difference for any comparison amongst the non-responders was detected. Of the responders, 9 of 31 (29%) exhibited high-risk features at baseline, compared with 5 of 13 (38%) in the non-responders. Sonographic response to ADA induction at 12 weeks significantly increases the likelihood of further response at 6 months. Responders also exhibited a significant reduction in CRP. High-risk features on baseline US may indicate increased likelihood for non-response. Measurement of 12-week US response may help guide early treatment optimisation.

Summary Background Vedolizumab is an α4β7 integrin antagonist with proven efficacy for inducing and maintaining clinical response and remission in Crohn's disease ( CD ) and ulcerative colitis ( UC ). Aim To evaluate clinical and objective response and remission rates with vedolizumab in a large, real world cohort. Methods A retrospective cohort study of adult CD and UC patients receiving vedolizumab between 2012 and 2017 was conducted. Primary outcome: clinical or objective response and remission at 3, 6 and 12 months after induction. Clinical remission was defined by complete, steroid‐free absence of symptoms. Objective remission was defined by endoscopic mucosal healing or normalisation of radiographic appearance on contrast‐enhanced ultrasound or CT / MR enterography. Results The study included 222 vedolizumab patients (122 CD , 100 UC ). In CD , clinical remission at 3, 6 and 12 months was achieved in 19.8% (22/111), 22.1% (21/95) and 22.1% (15/68) of patients, respectively. Objective remission occurred in 11.5% (6/52), 21.2% (14/66), and 18.9% (7/37) of patients at 3, 6 and 12 months, respectively. In UC , clinical remission at 3, 6, and 12 months was 51.0% (51/100), 61.8% (55/89) and 61.9% (39/63), respectively. Endoscopic remission occurred in 27.5% (11/40), 41.0% (16/39) and 47.8% (22/46) of patients at 3, 6 and 12 months, respectively. In multivariable analysis, patients with UC as compared to CD , and those with milder disease activity were more likely to achieve objectively defined remission at both 6 and 12 months. Conclusions Vedolizumab was effective for induction and maintenance of clinical and objective remission, both in Crohn's disease and ulcerative colitis.