Randomized Trial of Patient Outreach Approaches to De-implement Outdated Colonoscopy Surveillance Intervals.

BACKGROUND AND AIMS: Guidelines now recommend patients with low-risk adenomas receive colonoscopy surveillance in 7-10 years and those with the previously recommended 5-year interval be re-evaluated. We tested 3 outreach approaches for transitioning patients to the 10-year interval recommendation. METHODS: This was a 3-arm pragmatic randomized trial comparing telephone, secure messaging, and mailed letter outreach. The setting was Kaiser Permanente Northern California, a large integrated healthcare system. Participants were patients 54-70 years of age with 1-2 small (<10 mm) tubular adenomas at baseline colonoscopy, due for 5-year surveillance in 2022, without high-risk conditions, and with access to all 3 outreach modalities. Patients were randomly assigned to the outreach arm (telephone [n = 200], secure message [n = 203], and mailed letter [n = 201]) stratified by age, sex, and race/ethnicity. Outreach in each arm was performed by trained medical assistants (unblinded) communicating in English with 1 reminder attempt at 2-4 weeks. Participants could change their assigned interval to 10 years or continue their planned 5-year interval. RESULTS: Sixty-day response rates were higher for telephone (64.5%) and secure messaging outreach (51.7%) vs mailed letter (31.3%). Also, more patients adopted the 10-year surveillance interval in the telephone (37.0%) and secure messaging arms (32.0%) compared with mailed letter (18.9%) and rate differences were significant for telephone (18.1%; 97.5% confidence interval: 8.3%-27.9%) and secure message outreach (13.1%; 97.5% confidence interval: 3.5%-22.7%) vs mailed letter outreach. CONCLUSIONS: Telephone and secure messaging were more effective than mailed letter outreach for de-implementing outdated colonoscopy surveillance recommendations among individuals with a history of low-risk adenomas in an integrated healthcare setting. (ClinicalTrials.gov, Number: NCT05389397).

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Crohn's Disease.

BACKGROUND & AIMS: Biomarkers are used frequently for evaluation and monitoring of patients with Crohn's disease (CD). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of CD. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to formulate patient-centered clinical questions and review evidence on the performance of fecal calprotectin, serum C-reactive protein (CRP), and Endoscopic Healing Index in patients with established CD who were asymptomatic, had symptoms of varying severity, or were in surgically induced remission. Biomarker performance was assessed against the gold standard of endoscopic activity, defined as a Simple Endoscopic Score for Crohn's Disease ≥3. The panel used the Grading of Recommendations Assessment, Development and Evaluation Evidence-to-Decision framework to develop recommendations for use of biomarkers in various settings. Implementation considerations were formulated for each recommendation to inform clinical practice. RESULTS: The guideline panel made 11 conditional recommendations. In patients with CD in symptomatic remission, the panel suggests use of a biomarker- and symptom-based monitoring strategy over symptoms alone. In patients in symptomatic remission, a fecal calprotectin <150 µg/g and normal CRP rules out active inflammation, avoiding endoscopic evaluation for assessment of disease activity. However, elevated biomarkers in this setting merit confirmation with endoscopy before treatment adjustment. In patients with CD with mild symptoms, neither normal nor elevated biomarkers alone are sufficiently accurate to determine endoscopic activity. In patients with CD with moderate to severe symptoms, elevated fecal calprotectin or serum CRP suggests endoscopic activity, precluding routine endoscopic assessment for disease activity. In patients with CD in surgically induced remission in low-risk patients on pharmacologic prophylaxis, a normal fecal calprotectin reliably rules out endoscopic recurrence. In other postoperative settings, the panel suggests endoscopic assessment for establishing postoperative recurrence. CONCLUSIONS: In patients with CD, fecal calprotectin and serum CRP can inform disease management in both asymptomatic and symptomatic disease. Discordance between symptom assessment and biomarker value may merit endoscopic evaluation for confirmation of status of disease activity.

Common Instances of Low-value Care in Inflammatory Bowel Diseases.

Value-based care focuses on improving the quality, effectiveness, and efficiency of health care while controlling costs. Low-value care implies services or interventions that provide little or no benefit to patients, have the potential to cause harm, incur unnecessary cost to patients, or waste limited health care resources. In this review, we discuss common instances of low-value care along the spectrum of management in inflammatory bowel diseases (IBD). These include low value care in: (1) diagnosis and monitoring of IBD: utilization of serological markers to screen and diagnose IBD, over-reliance on symptoms for monitoring disease, failure to employ treat-to-target strategies in symptomatic patients with IBD, and annual surveillance colonoscopies in patients at low risk of developing dysplasia; (2) treatment of IBD: use of 5-aminosalicylates in Crohn's disease, continuation of 5-aminosalicylates after escalation to immunosuppressive therapy, chronic corticosteroid use without steroid-sparing strategies, step therapy for Crohn's disease, failure to optimize tumor necrosis factor antagonists in patients with active disease and subsequently de-intensification of therapies in those who have achieved stable remission; and (3) management of hospitalized patients with IBD: routine cross-sectional imaging for patients with IBD presenting to the emergency department, withholding pharmacological prophylaxis for venous thromboembolism in patients hospitalized with IBD flare, and prolonged use of high-dose intravenous corticosteroids in patients with acute severe ulcerative colitis. This review is meant to bring attention to value-based care in IBD and provide guidance to treating practitioners. Future studies on systematic evaluation of high- and low-value care in patients with IBD are warranted.

The Contemporary Probability of Occult Colorectal Cancer in Patients With Colitis-Related Dysplasia Undergoing Colectomy.

Occult colorectal cancer (CRC) has historically driven recommendations for colectomy in patients with inflammatory bowel disease with dysplasia . We defined the contemporary risk of occult CRC at colectomy among 93 patients with inflammatory bowel disease with dysplasia based on endoscopic appearance, resection, and concordance between site of cancer at colectomy and dysplasia at colonoscopy. Contrary to our hypothesis, we found that occult CRC at colectomy remains elevated in high-grade polypoid and invisible dysplasia. It was infrequent in other visible lesions. When present, occult cancer occurred in the same segment as dysplasia, suggesting the historic concern of missing a remote cancer is low.

Increased Risk of Hospitalization, Surgery, and Venous Thromboembolism Among Patients With Inflammatory Bowel Disease and Malnutrition in a Large, Community-Based Health Care System.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) constitute a high-risk population for malnutrition. Routine screening with standardized tools is recommended but can be challenging. Outcome data specific to IBD are sparse. METHODS: We performed a retrospective cohort study (2009-2019) and electronically screened a large community-based population with IBD for malnutrition risk by extracting height and longitudinal weight, data elements used in the Malnutrition Universal Screening Tool (MUST). We used Cox proportional hazards regression to evaluate whether an electronic medical record-derived modified MUST malnutrition risk score was associated with IBD-related hospitalization, surgery, and venous thromboembolism. RESULTS: Malnutrition risk was categorized as low in 10,844 patients with IBD (86.5%), medium in 1,135 patients (9.1%), and high in 551 patients (4.4%). In the 1-year follow-up period, medium and high malnutrition risks, compared with low risk, were associated with IBD-related hospitalization (medium-risk adjusted hazard ratio [aHR] 1.80, 95% confidence interval [CI] 1.34-2.42; high-risk aHR 1.90, 95% CI 1.30-2.78) and IBD-related surgery (medium risk aHR 2.28, 95% CI 1.60-3.26; high risk aHR 2.38, 95% CI 1.52-3.73). Only high malnutrition risk was associated with venous thromboembolism (aHR 2.79, 95% CI 1.33-5.87). DISCUSSION: Malnutrition risk is significantly associated with IBD-related hospitalization, surgery, and venous thromboembolism. Application of the MUST score to the electronic medical record can efficiently identify patients at risk for malnutrition and adverse outcomes, permitting concentration of nutritional and nonnutritional resources to those at greatest risk.

AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis.

BACKGROUND & AIMS: Biomarkers are used frequently for noninvasive monitoring and treatment decision making in the management of patients with ulcerative colitis (UC). This American Gastroenterological Association (AGA) guideline is intended to support practitioners in decisions about the use of biomarkers for the management of UC. METHODS: A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework to prioritize clinical questions, identify patient-centered outcomes, and conduct an evidence synthesis on the clinical performance of serum C-reactive protein (CRP), fecal calprotectin, and fecal lactoferrin as biomarkers of disease activity in patients with established UC in symptomatic remission or with active symptoms. The guideline panel used the Evidence-to-Decision framework to develop recommendations for the use of biomarkers for monitoring and management of UC and provided implementation considerations for clinical practice. RESULTS: The guideline panel made 7 conditional recommendations. In patients with UC in symptomatic remission, the panel suggests the use of a biomarker- and symptom-based monitoring strategy over a symptom-based monitoring strategy. For patients in symptomatic remission, the panel suggests using fecal calprotectin <150 µg/g, normal fecal lactoferrin, and/or normal CRP to rule out active inflammation and avoid routine endoscopic assessment of disease. In patients with UC with moderate to severe symptoms, the panel suggests using fecal calprotectin >150 µg/g, elevated fecal lactoferrin, or elevated CRP to inform treatment decisions and avoid routine endoscopic assessment of disease. However, in patients in symptomatic remission but elevated biomarkers, and in patients with moderate to severe symptoms with normal biomarkers, the panel suggests endoscopic assessment of disease to inform treatment decisions. In patients with UC with mild symptoms, the panel suggests endoscopic assessment of disease activity to inform treatment decisions. The panel identified the use of a biomarker-based monitoring strategy over an endoscopy-based monitoring strategy as a knowledge gap. The panel also proposed key implementation considerations for optimal use of biomarkers, and identified areas for future research. CONCLUSIONS: In patients with UC, noninvasive biomarkers, including fecal calprotectin, fecal lactoferrin, and serum CRP can inform disease monitoring and management.

Declining Colectomy Rates for Nonmalignant Colorectal Polyps in a Large, Ethnically Diverse, Community-Based Population.

INTRODUCTION: Despite studies showing improved safety, efficacy, and cost-effectiveness of endoscopic resection for nonmalignant colorectal polyps, colectomy rates for nonmalignant colorectal polyps have been increasing in the United States and Europe. Given this alarming trend, we aimed to investigate whether colectomy rates for nonmalignant colorectal polyps are increasing or declining in a large, integrated, community-based healthcare system with access to advanced endoscopic resection procedures. METHODS: We identified all individuals aged 50-85 years who underwent a colonoscopy between 2008 and 2018 and were diagnosed with a nonmalignant colorectal polyp(s) at the Kaiser Permanente Northern California integrated healthcare system. Among these individuals, we identified those who underwent a colectomy for nonmalignant colorectal polyps within 12 months after the colonoscopy. We calculated annual colectomy rates for nonmalignant colorectal polyps and stratified rates by age, sex, and race and ethnicity. Changes in rates over time were tested by the Cochran-Armitage test for a linear trend. RESULTS: Among 229,730 patients who were diagnosed with nonmalignant colorectal polyps between 2008 and 2018, 1,611 patients underwent a colectomy. Colectomy rates for nonmalignant colorectal polyps decreased significantly from 125 per 10,000 patients with nonmalignant polyps in 2008 to 12 per 10,000 patients with nonmalignant polyps in 2018 (P < 0.001 for trend). When stratified by age, sex, and race and ethnicity, colectomy rates for nonmalignant colorectal polyps also significantly declined from 2008 to 2018. DISCUSSION: In a large, ethnically diverse, community-based population in the United States, we found that colectomy rates for nonmalignant colorectal polyps declined significantly over the past decade likely because of the establishment of advanced endoscopy centers, improved care coordination, and an organized colorectal cancer screening program.

Prior Immunosuppressive Therapy and Severe Illness Among Patients Diagnosed with SARS-CoV-2: a Community-Based Study.

BACKGROUND: An estimated 10 million people in the USA are immunocompromised, a risk factor for severe COVID-19. Data informing whether immune-mediated medications lead to more severe infection are sparse. OBJECTIVE: Determine whether outpatient immunosuppressive therapies that treat autoimmune inflammatory disease or prevent solid organ transplant rejection are associated with severe illness after diagnosis with SARS-CoV-2 DESIGN: Retrospective cohort study PARTICIPANTS: Adults with a positive PCR nasal swab for SARS-CoV-2 from February 25 to September 9, 2020, cared for within a large integrated health care organization MAIN MEASURES: Exposure was defined as an outpatient fill of prednisone, immunomodulator, small-molecule, or biologic therapy in the 105 days prior to a positive SARS-CoV-2 PCR test. The main outcome was either hospitalization, ICU admission, or death within 45 days after diagnosis of SARS-CoV-2. Multivariable logistic regression models were adjusted for age, race, gender, body mass index, comorbidities, and autoimmune disease. KEY RESULTS: A total of 39,686 adults had a positive PCR test. In the primary analysis, prior prednisone use was associated with severe illness after diagnosis with SARS-CoV-2 (odds ratio (OR) 1.31; 95% confidence interval (CI) 1.08-1.60); however, immunomodulator (OR 0.88; 95% CI 0.57-1.34) and biologic/small-molecule therapy (OR 1.26; 95% CI 0.79-2.00) were not. Secondary analyses showed variable risk among therapies: Janus-kinase inhibitors had an increased odds of severe illness (OR 3.35; 95% CI 1.16-9.67), thiopurines/conventionaldisease-modifying antirheumatic drugs had a reduced odds (OR 0.53; 95% CI 0.32-0.88), and tumor necrosis factor inhibitors were not associated (OR 0.45; 95% CI 0.18-1.08). CONCLUSIONS AND RELEVANCE: Outpatient use of prednisone is associated with severe illness after diagnosis of SARS-CoV-2. Immunomodulator and biologic/small-molecule therapy were not associated, but different risk subgroups were identified. Our findings can inform risk-benefit discussions in the clinic and risk-based recommendations for patients on these therapies.

AGA Clinical Practice Update on Endoscopic Surveillance and Management of Colorectal Dysplasia in Inflammatory Bowel Diseases: Expert Review.

Improvements in disease management, as well as endoscopic technology and quality, have dramatically changed the way in which we conceptualize and manage inflammatory bowel disease-related dysplasia over the past 20 years. Based on evolving literature, we propose a conceptual model and best practice advice statements for the prevention, detection, and management of colorectal dysplasia in people with inflammatory bowel disease. This expert review was commissioned and approved by the American Gastroenterological Association Institute Clinical Practice Updates Committee and the American Gastroenterological Association Governing Board to provide timely guidance on a topic of high clinical importance to the American Gastroenterological Association membership. It underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Gastroenterology.

Retrospective Cohort Study Comparing Infliximab-dyyb and Infliximab in Biologic-Naive Patients With Inflammatory Bowel Disease in the United States.

Background: Real-world assessments of biosimilars are needed to understand their effectiveness and safety in practice settings that may differ from those seen in clinical trials or healthcare systems in different countries. To assess the effectiveness and safety of a biosimilar (infliximab-dyyb) and its reference product (infliximab) in patients with inflammatory bowel disease (IBD) in the United States. Methods: We conducted a retrospective cohort study of biologic-naive patients with IBD who started treatment with infliximab-dyyb or infliximab. The study included 3206 patients identified through electronic health records in a US integrated healthcare delivery system. The effectiveness outcome was a composite of IBD-related surgery, IBD-related emergency room visit, and IBD-related hospitalization within 12 months of initiation. Safety outcomes included incidence of any or serious infection, cancer, acute liver dysfunction, and tuberculosis. We used a non-inferiority test with an upper-limit margin of 10% to analyze effectiveness. Doubly robust methods incorporating Cox proportional hazard regression with standardized inverse probability of treatment weighting were used to analyze both effectiveness and safety outcomes. Results: The composite effectiveness outcome occurred in 107 of 870 patients (12.3%) in the infliximab-dyyb and 379 of 2336 patients (16.2%) in the infliximab groups. Infliximab-dyyb was non-inferior (P < .01) and was not different (hazard ratio [HR] 0.81; confidence interval [CI] 0.65-1.01; P = .06) to infliximab. Safety outcomes were not different between infliximab-dyyb and infliximab for any infections (HR 1.01; CI 0.86-1.17; P = .95), serious infections (HR 0.83; CI 0.54-1.26; P = .38), cancers (HR 0.83; CI 0.44-1.54; P = .55), and tuberculosis (HR 0.59; CI 0.10-3.55; P = .57). Conclusions: Initiation of infliximab-dyyb was non-inferior to infliximab among biologic-naive patients with IBD in an US integrated healthcare delivery system.

Effectiveness of Switching from Reference Product Infliximab to Infliximab-Dyyb in Patients with Inflammatory Bowel Disease in an Integrated Healthcare System in the United States: A Retrospective, Propensity Score-Matched, Non-Inferiority Cohort Study.

PURPOSE: The aim was to compare outcomes in adult patients with inflammatory bowel disease (IBD) who switched to infliximab-dyyb with those who remained on reference product (RP) infliximab in the United States (US) in a retrospective, propensity score-matched, non-inferiority cohort trial. METHODS: This study was a retrospective, non-inferiority study conducted within a US integrated healthcare system and included adult patients with a confirmed diagnosis of Crohn's disease or ulcerative colitis. A 1:1 propensity score matching was utilized to match patients who switched to infliximab-dyyb during the period April 2016-March 2018 to patients who remained on RP infliximab. The non-inferiority margin was set at + 10% of the upper limit. The primary outcome was a composite measure of disease worsening requiring acute care after the index date of switching to infliximab-dyyb or continuing RP infliximab. Disease worsening requiring acute care was defined as any IBD-related emergency room visit, hospitalization, or surgery. The secondary outcome was the composite measure of disease worsening requiring acute care or treatment failure. A switch to another biologic or tofacitinib was a proxy for treatment failure. All patients were followed for up to 9 months. RESULTS: After propensity score matching, the matched cohort included 1409 patients in the infliximab-dyyb group and 1409 patients in the RP infliximab group. The overall mean age (± standard deviation) was 47.7 ± 17.0 years, 50.9% of patients were of male gender, and 51.8% of patients had Crohn's disease, while the remainder of the cohort had ulcerative colitis. There were 144 patients (10.2%) in the infliximab-dyyb group and 245 patients (17.4%) in the RP infliximab group who experienced disease worsening requiring acute care (P < 0.01 for non-inferiority). There were 347 patients (24.6%) in the infliximab-dyyb group who experienced disease worsening requiring acute care or treatment failure compared to 375 patients (26.6%) who remained on RP infliximab (P < 0.01 for non-inferiority). CONCLUSION: There was no increased risk of (1) disease worsening requiring acute care or (2) disease worsening requiring acute care or treatment failure in patients with IBD who switched from RP infliximab to infliximab-dyyb when compared to patients who remained on RP infliximab in this US population. Infliximab-dyyb is an option for patients with IBD who need to use RP infliximab.

Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases.

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.

Appropriateness of Combination Therapy for Patients With Inflammatory Bowel Diseases: One Size Still Does Not Fit All.

Randomized controlled trials (RCTs) have demonstrated that therapies targeting tumor necrosis factor (TNF) and α4ß7 integrin are effective when given as monotherapy in inducing and/or maintaining remission in patients with ulcerative colitis (UC) or Crohn's disease (CD), but data from RCTs are less clear on whether concomitant immunomodulator (IM) therapy confers additional benefit. In CD, RCT data are mixed,1,2 as are results of systematic reviews and meta-analyses, showing no benefit overall,3 minimal benefit with individual agents,4 and comparative benefit over some monotherapies but not others.5 For example, concomitant azathioprine with infliximab is more effective than either drug alone in patients with CD naive to both drugs,2 but whether combination therapy is more effective than monotherapy with infliximab in nonnaive patients, or with other approved biologic drugs in any population, remains unknown. In UC, RCTs have shown that the benefit may be limited to specific populations,6 whereas systematic reviews suggest no benefit at all.7.