Therapeutic Drug Monitoring of Biologics in Crohn's Disease.

Reactive therapeutic drug monitoring (TDM) is considered the standard of care for optimizing biologics in inflammatory bowel disease (IBD) including Crohn's disease (CD). Preliminary data show that proactive TDM is associated with positive outcomes in IBD and can be also used to efficiently guide therapeutic decisions in specific clinical scenarios. Higher biological drug concentrations are associated with favorable therapeutic outcomes in specific IBD populations or phenotypes including pediatric CD, perianal fistulizing CD, small bowel CD, and following an ileocolonic resection for CD. Future perspectives of TDM include the use of rapid testing, pharmacogenomics, and pharmacokinetic dashboards toward individualized therapy.

Review article: emerging drug therapies in inflammatory bowel disease.

BACKGROUND: The landscape of inflammatory bowel disease (IBD) treatment is rapidly expanding with the development of new therapeutic options. AIM: To review the mechanisms of action and the available clinical trial data on emerging drug therapies for IBD. METHODS: Pubmed, Medline and Cochrane databases were queried up to July 2021 using keywords "inflammatory bowel disease," "IBD," "Crohn's disease," "ulcerative colitis" and "trial," "phase" and "study." In addition, we manually reviewed the grey literature including clinical trial registries and abstracts from major gastroenterology conferences in 2020 and 2021 to include pertinent information. RESULTS: In ulcerative colitis (UC), phase 2b and/or phase 3 studies met primary endpoints for S1P receptor agonists (estrasimod, ozanimod), anti-IL-23 agent (mirikizumab), anti-lymphocyte trafficking agents (ontamalimab, subcutaneous vedolizumab), JAK inhibitors (upadacitinib, filgotinib) and TLR9 agonist (cobitolimod). In Crohn's disease (CD), anti-IL-23 agents (risankizumab, mirikizumab, guselkumab), JAK inhibitors (upadacitinib, filgotinib) and anti-lymphocyte trafficking agents (ontamalimab, etrolizumab) met primary endpoints in randomised controlled clinical trials. CONCLUSION: Several new IBD drug therapies have positive efficacy and safety data in early clinical trials, and there are several drugs in the therapeutic pipeline. As more treatments for CD and UC are approved for clinical use, research to assess predictors of response to therapy and head-to-head trials is needed to inform providers on how to best position therapeutic options for patients with IBD.

Patients over Age 75 Are at Increased Risk of Emergency Department Visit and Hospitalization Following Colonoscopy.

BACKGROUND: The age to stop screening or surveillance colonoscopy is not well established, and unplanned hospital use after colonoscopy in the elderly is not well understood. AIMS: To evaluate unplanned emergency department (ED) visits and hospitalization in patients over 75 within 7 days of outpatient colonoscopy. METHODS: In this retrospective, single-center, cohort study, we reviewed outpatient screening or surveillance colonoscopies in patients ≥ 50 in a tertiary care academic medical center or affiliated facility between January 2008 and September 2013. Colonoscopies were divided by age based on USPSTF recommendations. The rate of ED visits and hospitalizations per colonoscopy for each age-group was determined. Predictors of ED visit and hospitalization were assessed through univariate and multivariate logistic regressions, and mortality following colonoscopy was evaluated using Kaplan-Meier analysis. RESULTS: A total of 30,409 colonoscopies were performed in 27,173 patients (51% male) by 40 endoscopists. ED visits occurred after 188 colonoscopies (0.62%). Age over 75 years was independently associated with ED visit (OR 1.58, 95% CI 1.05-2.37, p = 0.027) and hospitalization (OR 3.7, 95% CI 2.03-6.73, p < 0.001) within 7 days of colonoscopy. Higher number of medication classes, recent ED visit, polypectomy, and endoscopic mucosal resection were also independent variables associated with ED utilization after procedure. The mortality rate at the end of the follow-up (median 4.4; IQR 2.7-6 years) was 1.9, 8.6, and 15.8% for the age-groups 50-75, 76-85, and > 85 years, respectively. CONCLUSION: Patients over age 75 are 1.6 times as likely to use the ED and 3.7 times as likely to be hospitalized after colonoscopy. Further prospective studies are needed to assess the risk/benefit of nondiagnostic colonoscopy in geriatric patients.

Predictors of post-colonoscopy emergency department use.

BACKGROUND AND AIMS: Unplanned hospital visits within 7 days of colonoscopy were recently proposed as a quality measure. It is unknown whether patient, procedure, or endoscopist characteristics predict post-colonoscopy emergency department (ED) visits. Our aim was to determine the incidence and relatedness of ED visits within 7 days of colonoscopy and to identify predictors of post-colonoscopy ED use. METHODS: In this retrospective, single-center, cohort study, we evaluated outpatient colonoscopies performed at a tertiary academic medical center or affiliated facility between January 2008 and September 2013. We determined the incidence of ED visits within 7 days of colonoscopy and the relatedness of the ED visit to the procedure. We assessed for independent factors associated with ED use within 7 days using logistic regression analysis. RESULTS: We reviewed 50,319 colonoscopies performed on 44,082 individuals (47% male, median age 59 years) by 40 endoscopists. There were 382 (0.76%) ED visits after colonoscopy, of which 68% were related to the procedure. On multivariate analysis, recent ED visit (odds ratio [OR], 16.60; 95% confidence interval [CI], 12.83-21.48; P < .001), EMR (OR, 4.69; 95% CI, 2.82-7.79; P < .001), number of medication classes (OR, 1.18; 95% CI, 1.11-1.26; P < .001), endoscopist adenoma detection rate (ADR) (OR, 1.14; 95% CI, 1.01-1.29; P = .029), and white race (OR, 0.77; 95% CI, 0.62-0.97; P = .028) were identified as independent variables associated with ED visits after colonoscopy. CONCLUSIONS: Increased patient complexity, higher endoscopist ADR, and EMR were associated with increased ED use after colonoscopy. Patients at high risk for an unplanned hospital visit within 7 days should be targeted for quality improvement efforts to reduce adverse events and cost.

A National Survey of the Prevalence and Impact of Cytomegalovirus Infection Among Hospitalized Patients With Ulcerative Colitis.

GOALS: To estimate the effect of cytomegalovirus (CMV) in patients with ulcerative colitis (UC), and compare these outcomes to patients with CMV without UC. BACKGROUND: The impact of CMV infection in UC is not well understood. STUDY: We analyzed records from the Nationwide Inpatient Sample (NIS) of patients with UC and CMV between 2006 and 2012. Differences in outcomes were determined between patients with UC and CMV and those with UC without CMV. Secondary analysis compared outcomes of patients with UC and CMV to patients with CMV alone. RESULTS: Patients with UC and CMV (n=145) had longer length of stay (16.31 vs. 5.52 d, P<0.0001), higher total charges ($111,835.50 vs. $39.895, P=0.001), and were less likely to be discharged home without services (50.0% vs. 81.83%, P<0.0001) compared with patients with UC without CMV (n=32,290). On regression analysis, CMV was significantly associated with higher total charges (P<0.01) and longer length of stay (P<0.01), but not for increased need for colorectal surgery. When comparing patients with UC and CMV to patients with CMV alone (n=14,960), patients with CMV alone had a higher Charlson Comorbidity Index and a trend toward higher in-hospital mortality. CONCLUSIONS: CMV infection in hospitalized patients with UC is associated with a longer length of stay, increased total charges, and fewer routine discharges, but not increased surgery or mortality. Patients with CMV alone had the worst outcomes of all groups suggesting that CMV in UC patients may not have the same negative impact as in other diseases.

A Survey Study of Gastroenterologists' Attitudes and Barriers Toward Therapeutic Drug Monitoring of Anti-TNF Therapy in Inflammatory Bowel Disease.

Background: Therapeutic drug monitoring (TDM) may improve the efficacy and cost-effectiveness of anti-TNF therapy. A standardized approach of utilizing TDM has not been established. The objective of this study was to determine gastroenterologists' attitudes and barriers toward TDM of anti-TNF therapy in clinical practice. Methods: An 18-question survey was distributed to members of the American College of Gastroenterology and Crohn's and Colitis Foundation via email. We collected physician characteristics, practice demographics, and data regarding TDM use and perceived barriers to TDM. Factors associated with the use of TDM were determined by logistic regression analysis. Results: A total of 403 gastroenterologists from 42 US states (76.4% male) met inclusion criteria: 90.1% use TDM, mostly reactively for secondary loss of response (87.1%) and primary nonresponse (66%); 36.6% use TDM proactively. The greatest barriers to TDM implementation were uncertainty about insurance coverage (77.9%), high out-of-pocket patient costs (76.4%), and time lag from serum sample to result (38.5%). Factors independently associated with the use of TDM and proactive TDM were practice in an academic setting (P = 0.019), and more IBD patients seen per month (P = 0.015), and Crohn's and Colitis Foundation membership (P < 0.001), and more IBD patients on anti-TNF therapy per month (P = 0.006), respectively. If all barriers were removed, an additional one-third of physicians would apply proactive TDM. Conclusions: Lack of insurance coverage, high out-of-pocket costs, and the time lag from test to result limit use of TDM in the United States. Validation of low-cost assays, point of care testing, and studies that standardize the use of TDM are needed to make TDM more commonplace.

The Effect of Right Colon Retroflexion on Adenoma Detection: A Systematic Review and Meta-analysis.

BACKGROUND: Although colonoscopy with polypectomy can prevent up to 80% of colorectal cancers, a significant adenoma miss rate still exists, particularly in the right colon. Previous studies addressing right colon retroflexion have revealed discordant evidence regarding the benefit of this maneuver on adenoma detection with concomitant concerns about safety and rates of maneuver success. In this meta-analysis, we sought to determine the effect of right colon retroflexion on improving adenoma detection compared with conventional colonoscopy without retroflexion, as well as determine the rates of retroflexion maneuver success and adverse events. METHODS: Multiple databases including MEDLINE, Embase, and Web of Science were searched for studies on right colon retroflexion and its impact on adenoma detection compared with conventional colonoscopy. Pooled analyses of adenoma detection and retroflexion success were based on mixed-effects and random-effects models with heterogeneity analyses. RESULTS: Eight studies met the inclusion criteria (N=3660). The primary analysis comparing colonoscopy with right-sided retroflexion versus conventional colonoscopy to determine the per-adenoma miss rate in the right colon was 16.9% (95% confidence interval, 12.5%-22.5%). The overall rate of successful retroflexion was 91.9% (95% confidence interval, 86%-95%) and rate of adverse events was 0.03%. CONCLUSIONS: Colonoscopy with right-sided retroflexion significantly increases the detection of adenomas in the right colon compared with conventional colonoscopy with a high rate of maneuver success and small risk of adverse events. Thus, reexamination of the right colon in retroflexed view should be strongly considered in future standard of care colonoscopy guidelines for quality improvement in colon cancer prevention.