It is uncertain whether patients with ulcerative colitis (UC) and delayed symptomatic response to therapy have as robust and durable a response as earlier responders to therapy. We compared clinical ...outcomes of early and delayed responders to vedolizumab and adalimumab for patients with moderate-severe UC.
This was a post hoc analysis of the VARSITY study. Patients with early partial Mayo score (PMS) remission (PMS ≤1 at week 4/6 of therapy) were compared with those with delayed PMS remission (PMS ≤1 at week 14 and not week 4/6). Differences in proportions of patients achieving week 52 clinical remission (CR) (PMS = 0), endoscopic improvement (EI) (Mayo endoscopic subscore ≤1), and histoendoscopic mucosal improvement (HEMI) (Mayo endoscopic subscore ≤1 and Geboes score highest grade <3.2) were assessed. Confounders were adjusted for using multivariate logistic regression.
A total of 147 vedolizumab-treated and 110 adalimumab-treated patients attained early or late PMS remission. Those who attained early PMS remission with vedolizumab were more likely to attain week 52 CR than participants with delayed PMS remission with vedolizumab (69.1% 67/97 vs 50.0% 25/50, aOR 2.43 95% CI 1.11-5.33, P = 0.027). Week 52 HEMI was more likely among early vedolizumab PMS remitters (63.9% 62/97 vs 40.0% 20/50, aOR 2.60 95% CI 1.20-5.62, P = 0.015). Week 52 EI was similar between early and delayed PMS remitters to vedolizumab. No differences were observed in week 52 CR, EI, or HEMI between early and delayed PMS remitters to adalimumab.
Patients with UC who achieve early PMS remission with vedolizumab have greater odds of week 52 remission compared with delayed responders.
It is unclear how baseline endoscopic characteristics in Crohn's disease (CD) affect the ability to achieve endoscopic remission (ER). We aimed to determine the endoscopic prognostic factors that ...influence achieving ER in CD.
This post hoc analysis of SONIC (NCT00094458; YODA #2019-3980) evaluated baseline and week 26 endoscopy indices in 172 patients using the CD Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for CD. The impact of baseline ulcer depth and size on achieving week 26 ER was assessed using multivariate logistic regression models adjusted for confounders.
The ER rate of ileal ulcers was significantly lower than ER rates throughout the colon (P < 0.0001). Ileal ulcers >2 cm were less likely to achieve ER compared with smaller ulcers {odds ratio (OR) 0.31 (95% confidence interval CI 0.11-0.89), P = 0.03}. Similarly, rectal ulcers >2 cm were associated with reduced odds of week 26 ER (OR 0.26 95% CI 0.08-0.80, P = 0.02). Ulcer size in other colonic segments did not affect the achievement of week 26 ER. Deep ileal and rectal ulcers >2 cm compared with smaller or superficial ulcers were even less likely to achieve week 26 ER (ileum: OR 0.10, 95% CI 0.02-0.68, P = 0.02; rectum: OR 0.12, 0.02-0.82, P = 0.03). High baseline Simple Endoscopic Score for CD (≥16) or CDEIS scores (≥12) did not affect achieving week 26 ER.
Patients with larger and deep ulcers in the ileum or rectum may have difficulty achieving ER. Overall degree of endoscopic inflammation as measured numerically by endoscopic scores does not affect the likelihood of achieving week 26 ER.
Cost-effectiveness of biomarker- vs endoscopy-based treat-to-target monitoring in Crohn's disease (CD) is unknown.
A microsimulation model for CD was built to simulate biomarker (fecal calprotectin) ...vs endoscopy-based monitoring in a treat-to-target fashion. Published literature in combination with patient-level data from phase 3 clinical trials and population estimates for therapeutic drug monitoring were used to generate transition probabilities, costs, and utilities. Tracker variables were used to modify downstream probabilities and outcomes based on previous exposures, response patterns, and disease-related complications or surgery history. The primary outcome was cost-effectiveness over a 5-year horizon at a willingness-to-pay threshold of $100,000/quality-adjusted life-year. Probabilistic sensitivity analyses in addition to multiple 1-, 2-, and 3-way microsimulation sensitivity analyses were performed.
In the base-case model, the endoscopy-based monitoring strategy dominated the biomarker-based monitoring strategy over a 5-year horizon. Over shorter periods of observation, the biomarker-based monitoring strategy became progressively more cost-effective, with cost-effectiveness achieved for this strategy over a 1-year horizon. Therapeutic drug monitoring did not influence short-term cost-effectiveness of biomarker-based monitoring. Once in endoscopic remission, continued biomarker-based vs endoscopy-based monitoring was more cost-effective. A hybrid biomarker-endoscopy-based monitoring strategy dominated the endoscopy-based monitoring strategy over a 5-year horizon. The strongest determinants for cost-effectiveness were cost of colonoscopy and diagnostic performance of fecal calprotectin.
The most cost-effective approach for treat-to-target monitoring in CD is up-front biomarker-based monitoring followed by endoscopy-based monitoring if not in endoscopic remission by 1 year and then returning to biomarker-based monitoring once in endoscopic remission.
We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD).
This study used a retrospective, multicenter, multinational consortium of UST-treated ...CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation.
A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma n = 1, arthralgia n = 6, rash n = 6, headache n = 3, hepatitis n = 3, hair loss n = 3, neuropathy n = 1, and vasculitis n = 1) occurred in 2.4% of patients.
UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.
We applied the Grading of Recommendations, Assessment, Development, and Evaluation framework to evaluate the performance of fecal calprotectin (FC) as an alternative to endoscopy in patients with ...moderate-to-severe ulcerative colitis (UC) treated with a biologic agent or tofacitinib.
Individual participant data from the trials of infliximab, golimumab, vedolizumab, and tofacitinib for UC were pooled to generate prevalence of endoscopic activity (Mayo endoscopy score) across different combinations of the rectal bleeding score (RBS) and stool frequency score (SFS). These estimates were then combined with the data from an updated systematic review of the operating properties of FC to generate clinical scenario-specific assessments of the performance of FC as a predictor of endoscopic disease activity. A prespecified threshold of acceptability for false-negative (FN) and false-positive (FP) test results was set at 5%.
For patients with UC achieving RBS 0 + SFS 0/1, FC ≤ 50 μg/g may avoid endoscopy in 50% patients with a FN rate <5%. Similarly, for patients with RBS 2/3 + SFS 2/3, FC ≥ 250 μg/g potentially avoids endoscopy in approximately 50% patients with an FP rate <5%. The greatest uncertainty in the diagnostic performance for FC was observed in patients with UC achieving RBS 0 but having SFS 2/3, where FN and FP rates were consistently >10%, and endoscopic evaluation may be warranted.
Two clinical scenarios were identified where FC can be used with confidence for monitoring treatment response to biologics or tofacitinib in patients with UC without the requirement for endoscopy.
Several studies have shown increased incidence, recurrence, and severity of Clostridium difficileinfection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI ...are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies.
This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI.
There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model.
Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.
Abstract The inflammatory state of atherosclerosis has been established as those with chronic inflammatory diseases, such as rheumatoid arthritis and systemic lupus erythematosus, who are at ...increased risk of coronary artery disease. A systematic search was conducted to retrieve high-quality, peer-reviewed studies of inflammatory bowel disease and coronary artery disease. Recent literature supports an association between inflammatory bowel disease and coronary artery disease. While hypertension increases the risk of coronary artery disease in inflammatory bowel disease patients, other typical risk factors have not been confirmed, and markers of inflammation may predict coronary artery disease risk in this population. Common cardiovascular drugs such as statins and angiotensin-converting enzyme inhibitors may have dual potential for controlling inflammatory bowel disease and preventing or treating coronary artery disease. Large, prospective, longitudinal studies can help to determine the true prevalence of coronary artery disease in this population and confirm risk factors. In the absence of such evidence, physicians should be cognizant of increased coronary artery disease risk in inflammatory bowel disease patients without traditional risk factors and consider primary preventive strategies.
Background. The majority of children who undergo gastrointestinal (GI) endoscopy require anesthesia or procedural sedation for comfort, cooperation, and procedure efficiency. The safety profile of ...propofol is not well established in children but has been studied in the literature. Objective. The aim of this study is to evaluate and compare the safety of propofol-only sedation for GI endoscopy procedures to other anesthetic regimes in the pediatric population. Methods. A search was conducted in the MEDLINE, Embase, and Cochrane Library databases. Randomized clinical trials and prospective cohorts were included in the study. Results. No significant difference was noted in total complications between the two cohorts with a pooled OR of 1.31 (95% CI: 0.57–3.04, chi2 = 0.053, I2 = 54.31%). The pooled rate of complications in the studies was 23.4% for those receiving propofol only and 18.2% for those receiving other anesthetic regimens. Sensitivity analysis was performed removing a study with a very different control comparison compared to the rest of the studies included. Once excluded, there was minimal heterogeneity in the remaining studies and a significant difference in overall complications was detected, with more complications seen in the propofol-only group compared to the other anesthetic groups (OR 1.87, 95% CI 1.09–3.20). Conclusion. Significantly higher incidence of cardiorespiratory complications was noted in the propofol-only versus other anesthetic regimens in pediatric patients undergoing GI endoscopy in this meta-analysis. However, the overall quality of the evidence is very low. How to Apply This Knowledge for Routine Clinical Practice. Clinicians providing sedation to a pediatric population for GI endoscopy should consider there may be increased risks when using a propofol-only regimen, but further study is needed.
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