Risk factors for incomplete telehealth appointments among patients with inflammatory bowel disease.

Background: The COVID-19 pandemic led to the urgent implementation of telehealth visits in inflammatory bowel disease (IBD) care; however, data assessing feasibility remain limited. Objectives: We looked to determine the completion rate of telehealth appointments for adults with IBD, as well as to evaluate demographic, clinical, and social predictors of incomplete appointments. Design: We conducted a retrospective analysis of all patients with IBD who had at least one scheduled telehealth visit at the NYU IBD Center between 1 March 2020 and 31 August 2021, with only the first scheduled telehealth appointment considered. Methods: Medical records were parsed for relevant covariables, and multivariable logistic regression was used to estimate the adjusted association between demographic factors and an incomplete telehealth appointment. Results: From 1 March 2020 to 31 August 2021, there were 2508 patients with IBD who had at least one telehealth appointment, with 1088 (43%) having Crohn's disease (CD), 1037 (41%) having ulcerative colitis (UC), and 383 (15%) having indeterminate colitis. Of the initial telehealth visits, 519 (21%) were not completed, including 435 (20%) among patients <60 years as compared to 84 (23%) among patients ⩾60 years (p = 0.22). After adjustment, patients with CD had higher odds of an incomplete appointment as compared to patients with UC [adjusted odds ratio (adjOR): 1.37, 95% confidence interval (CI): 1.10-1.69], as did females (adjOR: 1.26, 95% CI: 1.04-1.54), and patients who had a non-first-degree relative listed as an emergency contact (adjOR: 1.69, 95% CI: 1.16-2.44). While age ⩾60 years was not associated with appointment completion status, we did find that age >80 years was an independent predictor of missed telehealth appointments (adjOR: 2.92, 95% CI: 1.12-7.63) when compared to individuals aged 60-70 years. Conclusion: Patients with CD, females, and those with less social support were at higher risk for missed telehealth appointments, as were adults >80 years. Engaging older adults via telehealth, particularly those aged 60-80 years, may therefore provide an additional venue to complement in-person care.

Comparative Safety of Biologic Agents in Patients With Inflammatory Bowel Disease With Active or Recent Malignancy: A Multi-Center Cohort Study.

BACKGROUND & AIMS: Safety of biologic agents is a key consideration in patients with inflammatory bowel disease (IBD) and active or recent cancer. We compared the safety of tumor necrosis factor (TNF)-α antagonists vs non-TNF biologics in patients with IBD with active or recent cancer. METHODS: We conducted a multicenter retrospective cohort study of patients with IBD and either active cancer (cohort A) or recent prior cancer (within ≤5 years; cohort B) who were treated with TNFα antagonists or non-TNF biologics after their cancer diagnosis. Primary outcomes were progression-free survival (cohort A) or recurrence-free survival (cohort B). Safety was compared using inverse probability of treatment weighting with propensity scores. RESULTS: In cohort A, of 125 patients (483.8 person-years of follow-up evaluation) with active cancer (age, 54 ± 15 y, 75% solid-organ malignancy), 10 of 55 (incidence rate [IR] per 100 py, 4.4) and 9 of 40 (IR, 10.4) patients treated with TNFα antagonists and non-TNF biologics had cancer progression, respectively. There was no difference in the risk of progression-free survival between TNFα antagonists vs non-TNF biologics (hazard ratio, 0.76; 95% CI, 0.25-2.30). In cohort B, of 170 patients (513 person-years of follow-up evaluation) with recent prior cancer (age, 53 ± 15 y, 84% solid-organ malignancy; duration of remission, 19 ± 19 mo), 8 of 78 (IR, 3.4) and 5 of 66 (IR 3.7) patients treated with TNFα antagonists and non-TNF biologics had cancer recurrence, respectively. The risk of recurrence-free survival was similar between both groups (hazard ratio, 0.94; 95% CI, 0.24-3.77). CONCLUSIONS: In patients with IBD with active or recent cancer, TNFα antagonists and non-TNF biologics have comparable safety. The choice of biologic should be dictated by IBD disease severity in collaboration with an oncologist.

A Serum Biomarker Panel Can Accurately Identify Mucosal Ulcers in Patients With Crohn's Disease.

BACKGROUND: The Endoscopic Healing Index (EHI) is a serum biomarker panel that can predict endoscopic inflammation in Crohn's disease (CD). METHODS: Paired serum samples with endoscopies from adult patients participating in a prospective biobank (June 2014 to December 2018) were analyzed post hoc. Diagnostic performance for EHI was assessed against the individual parameters of the Simple Endoscopic Score for CD using previously identified cutoffs. Confounders for EHI performance were identified using logistic regression. RESULTS: A total of 205 CD patients were included (50% male, median age 37 years). An EHI of 20 points was sensitive for ruling out any ulcers (85%; 95% confidence interval [CI], 77%-91%) and large (5-20 mm) or very large (>20 mm) ulcers (93%; 95% CI, 84%-97%). An EHI of 50 points was specific for ruling in any ulcers (86%; 95% CI, 76%-92%) and large or very large ulcers (87%; 95% CI, 79%-92%). After accounting for total extent of inflamed mucosa, strictures, and disease location, each 20-point increase in EHI was associated with a 1.7-fold increased probability for the presence of large or very large ulcers (adjusted odds ratio, 1.7; 95% CI, 1.1-2.6). CONCLUSIONS: The EHI was independently associated with ulcer size and accurately identified large or very large ulcers. A cutoff of 50 points can reliably rule in mucosal ulcers and allow for treatment adjustment. A cutoff of 20 points can reliably rule out mucosal ulcers and signal completion of treatment adjustment algorithms.

Cancer in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. Individuals with IBD are at increased risk for several malignancies originating in the intestine, such as colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, and anal cancer. There are also several extraintestinal malignancies associated with IBD and IBD therapies, including cholangiocarcinoma, skin cancer, hematologic malignancies, genitourinary cancer, cervical cancer, and prostate cancer. The authors summarize the risk of cancer in patients with IBD, diagnosis and management of colorectal neoplasia in IBD, and management of patients with IBD and active or recent cancer.

Spatial Evolution of Histologic and Endoscopic Healing in the Left and Right Colon in Patients With Ulcerative Colitis.

BACKGROUND AND AIMS: Despite increasing interest in histologic remission as a treatment target in ulcerative colitis (UC), the accuracy of histologic findings in left colon in detecting pancolonic histologic remission is unknown. METHODS: In a retrospective cohort study of patients with endoscopically active pancolitis undergoing treat-to-target interventions, we evaluated the diagnostic accuracy of left-sided (distal to splenic flexure) histologic and endoscopic findings on colonoscopy for detecting histologic and endoscopic healing elsewhere in the colon. RESULTS: Of 86 patients with moderate to severely active pancolitis who underwent 2 consecutive colonoscopies during treat-to-target interventions, 38% and 51% achieved histologic and endoscopic remission, respectively. Substantial agreement (kappa, 0.67; 95% confidence interval (CI), 0.51-0.83) was observed in histologic findings between left and right colon on follow-up colonoscopy. Histologic, and endoscopic, findings in left colon showed excellent accuracy in detecting pancolonic histologic remission (area under the curve (AUC), 0.96 [95% CI, 0.93-1.0]; misclassification rate, 5.9%), histologic normalization (AUC, 1.0, 0%), endoscopic improvement (AUC, 0.95 [0.96-1.0], 3.5%) and endoscopic remission (AUC, 0.98 [0.96-1.00], 5.8%), respectively. CONCLUSIONS: In patients with active pancolitis undergoing treat-to-target interventions, histologic and endoscopic findings in the left colon on colonoscopy have excellent accuracy for detecting pancolonic histologic remission, histologic normalization, endoscopic improvement, and endoscopic remission. Flexible sigmoidoscopy may suffice for monitoring histologic and endoscopic activity in patients with pancolitis.

Systematic review with meta-analysis: safety and tolerability of immune checkpoint inhibitors in patients with pre-existing inflammatory bowel diseases.

BACKGROUND: Immune checkpoint inhibitors may variably impact patients with pre-existing autoimmune diseases. AIMS: To evaluate the risks and outcomes of adverse events in patients with pre-existing inflammatory bowel diseases treated with immune checkpoint inhibitors. METHODS: Through a systematic literature review up until July 31, 2020, we identified 12 studies reporting the impact of immune checkpoint inhibitors in 193 patients with inflammatory bowel disease. Outcomes of interest were relapse of inflammatory bowel disease, need for corticosteroids and/or biologics to manage inflammatory bowel disease relapse, and discontinuation of immune checkpoint inhibitors. We calculated pooled rates (with 95% confidence intervals [CI]) using random effects meta-analysis, and examined risk factors associated with adverse outcomes through qualitative synthesis of individual studies. RESULTS: On meta-analysis, 40% patients (95% CI, 26%-55%) experienced relapse of inflammatory bowel disease with immune checkpoint inhibitors. Among patients who experienced relapse, 76% (95% CI, 65%-85%) required corticosteroids, and 37% (95% CI, 22%-53%) required biologic therapy. Overall, 35% patients (95% CI, 17%-57%) with inflammatory bowel disease discontinued immune checkpoint inhibitors. Gastrointestinal perforation and abdominal surgery due to immune checkpoint inhibitor complications occurred in <5% patients. In a large study, inhibitors of cytotoxic T-lymphocyte antigen-4 (CTLA-4) were associated with a higher risk of relapse than programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors. CONCLUSIONS: Approximately 40% of patients with pre-existing inflammatory bowel diseases experience relapse with immune checkpoint inhibitors, with most relapsing patients requiring corticosteroids and one-third requiring biologics. CTLA-4 inhibitors may be associated with higher risk of relapse.

Risk of Relapse in Patients With Ulcerative Colitis With Persistent Endoscopic Healing: A Durable Treatment Endpoint.

BACKGROUND: Deep remission in patients with UC has relied on initial achievement of biochemical, endoscopic, and/or histological remission. We evaluated persistent symptomatic remission and endoscopic healing (EH: Mayo endoscopy score [MES] 0 or 1) on consecutive endoscopic examinations as a durable treatment endpoint. METHODS: In a retrospective cohort study, we estimated and compared cumulative risk of clinical relapse in patients with persistent EH, with and without persistent histological remission and depth of EH, among adults with active UC treated-to-target of symptomatic remission and EH who achieved and maintained symptomatic remission and EH over two serial endoscopic assessments. We also explored risk of relapse in patients with persistent EH whose therapy was de-escalated. RESULTS: Of 270 patients who initially achieved EH with treatment-to-target, 89 maintained symptomatic remission and EH on follow-up endoscopy [interval between EH1 and EH2, 16 months]. On follow-up after EH2 [median, 19 months], 1-year cumulative risk of relapse in patients with persistent EH was 11.5%, and with persistent histological remission was 9.5%. Seventeen patients with persistent EH, who underwent de-escalation of therapy, did not have an increased risk of relapse as compared with patients who continued index therapy [5.3% vs 14%, p = 0.16]. CONCLUSIONS: Patients with active UC treated-to-target of clinical remission, who achieve and maintain symptomatic remission and EH over consecutive endoscopies, have a low risk of relapse, particularly in a subset of patients who simultaneously achieve histological remission. Persistent EH should be examined as a treatment endpoint suggestive of deep remission.

Baseline Clearance of Infliximab Is Associated With Requirement for Colectomy in Patients With Acute Severe Ulcerative Colitis.

BACKGROUND & AIMS: Hospitalized patients with acute severe ulcerative colitis (ASUC) often require surgery. Although the tumor necrosis factor antagonist infliximab is an effective salvage therapy to prevent colectomy in patients with ASUC, optimal dosing is unclear. Calculated infliximab clearance has been associated with important outcomes in patients with ulcerative colitis, but its utility in patients with ASUC has not been established. We assessed the relationship between calculated the baseline infliximab clearance before infliximab salvage therapy and the requirement for colectomy in patients hospitalized for ASUC. METHODS: We obtained data from hospitalized patients with ASUC who initiated infliximab therapy. We then calculated the baseline infliximab drug clearance in these patients based on an existing formula. The primary aim was to compare clearance between patients who required colectomy 6 months later and patients who did not require colectomy. Receiver operating characteristic curve analyses evaluated clearance thresholds for colectomy. Multivariable logistic regression analysis evaluated factors associated with colectomy. RESULTS: In 39 patients with ASUC, the median baseline calculated clearance was higher in patients requiring colectomy at 6 months than in patients without colectomy (0.733 vs 0.569 L/d; P = .005). An infliximab clearance threshold of 0.627 L/d identified patients who required colectomy with 80.0% sensitivity and 82.8% specificity (area under the curve, 0.80). A higher proportion of patients with infliximab clearance of 0.627 L/d or more underwent colectomy within 6 months (61.5%) than patients with lower infliximab clearance values (7.7%) (P = .001). Multivariable analysis identified baseline infliximab clearance as the only factor associated with colectomy. The infliximab dose in the hospital was higher in patients who required colectomy. Results were similar at 30 days and 1 year. CONCLUSIONS: In patients hospitalized with ASUC, higher values of calculated infliximab clearance before infliximab administration is associated with higher rates of colectomy. Although patients who required colectomies received higher doses, data on infliximab concentrations are lacking. Infliximab pharmacokinetic models are needed for patients with ASUC to allow comparative trials on clearance-based vs standard dosing.

Biomarkers are associated with clinical and endoscopic outcomes with vedolizumab treatment in Crohn's disease.

BACKGROUND: Vedolizumab, an α4ß7 integrin antagonist, is an effective therapy for Crohn's disease (CD). Biomarkers are needed to guide therapy and predict outcomes. This study evaluated biomarker concentrations and outcomes in patients with CD undergoing vedolizumab treatment. METHODS: Sera at weeks 0, 2, 6, 14, and ⩾26 were collected from vedolizumab-treated, refractory CD patients. Concentrations of soluble (s)-Vascular Cell Adhesion Molecule (VCAM)-1, s-Intercellular Cell Adhesion Molecule (ICAM)-1, s-Mucosal Addressin Cell Adhesion Molecule (MAdCAM)-1, and s-α4ß7 integrin were evaluated for associations with achieving endoscopic remission. RESULTS: A total of 22 patients with CD were included. In all patients, s-MAdCAM-1 decreased significantly and s-α4ß7 increased compared with baseline. s-VCAM-1 and s-ICAM-1 changed differentially in patients who achieved remission. At week 6, median s-VCAM-1 (859.6 ng/ml versus 460.3 ng/ml, p = 0.03) and s-ICAM-1 (545.7 ng/ml versus 286.2 ng/ml, p = 0.03) concentrations were higher in patients who achieved endoscopic remission compared with those who did not, and similar differences were observed for s-ICAM-1 concentrations in patients who achieved clinical remission, compared with those who did not (669.1 ng/ml versus 291.0 ng/ml, p = 0.04). Week 14 s-α4ß7 concentrations were lower in patients who achieved endoscopic remission, compared with those who did not (7.5 ng/ml versus 17.6 ng/ml, p = 0.020). CONCLUSION: In all vedolizumab-treated CD patients, s-MAdCAM-1 decreased significantly and s-α4ß7 increased. However, higher concentrations of s-ICAM-1 and s-VCAM-1 at week 6 and lower concentrations of s-α4ß7 at week 14 differentiated patients who achieved endoscopic remission. These findings may help identify early predictors of response to vedolizumab treatment in patients with CD. Further validation in less refractory CD patients is needed.

Effect of Lifestyle Factors on Outcomes in Patients With Inflammatory Bowel Diseases.

Various lifestyle factors including physical activity and obesity, stress, sleep, and smoking may modify the risk of developing inflammatory bowel diseases (IBDs). In patients with established IBD, these lifestyle factors may significantly impact the natural history and clinical outcomes. Recreational exercise decreases the risk of flare and fatigue in patients with IBD. In contrast, obesity increases the risk of relapse and is associated with higher anxiety, depression, fatigue, and pain and higher health care utilization. Obesity also modifies pharmacokinetics of biologic agents unfavorably and is associated with a higher risk of treatment failure. Sleep disturbance is highly prevalent in patients with IBD, independent of disease activity, and increases the risk of relapse and chronic fatigue. Similarly, stress, particularly perceived stress rather than major life events, may trigger symptomatic flare in patients with IBD, although its impact on inflammation is unclear. Cigarette smoking is associated with unfavorable outcomes including the risk of corticosteroid dependence, surgery, and disease progression in patients with Crohn's disease; in contrast, smoking does not significantly impact outcomes in patients with ulcerative colitis, although some studies suggest that it may be associated with a lower risk of flare. The effect of alcohol and cannabis use in patients with IBD is inconsistent, with some studies suggesting that cannabis may decrease chronic pain in patients with IBD, without a significant effect of biological remission. Although these lifestyle factors are potentially modifiable, only a few interventional studies have been conducted. Trials of structured exercise and psychological therapy including mindfulness-based therapies such as meditation and yoga and gut-directed hypnotherapy have not consistently demonstrated benefit in clinical and/or endoscopic disease activity in IBD, although may improve overall quality of life.

Overall and comparative safety of biologic and immunosuppressive therapy in inflammatory bowel diseases.

Introduction: Efficacy and safety are key aspects when choosing therapies for patients with inflammatory bowel diseases (IBD). While several randomized trials and indirect comparisons have informed the comparative efficacy of medications, there has been a limited synthesis of safety of different agents. Areas covered: We focus on the overall and comparative risk of serious and opportunistic infections and malignancy of biologic and immunosuppressive therapy in IBD, based on randomized trials, open-label extension and registry studies, and real-world comparative observational studies. Expert opinion: TNFα antagonists may be more immunosuppressive than non-TNF-targeted biologic agents and increase the risk of systemic infections. Most consistent risk factors for serious infections include use of combination therapy with immunosuppressive agents and/or corticosteroids, moderate to severe disease activity, and older age. TNFα antagonists may also be associated with an increased risk of lymphoma, especially when combined with thiopurines. Real-world comparative safety studies, especially with newer biologic agents, are warranted to inform decision-making. Comparative safety of pharmacotherapy for IBD should be viewed in conjunction with efficacy and in the context of treatment strategies/approach, rather than in the context of specific agents used.