We investigated whether treatment of active inflammatory bowel disease with biologic agents is associated with a reduced risk of venous thromboembolic events (VTEs) compared with corticosteroid ...therapy.
We performed a retrospective analysis of 15,100 adults with inflammatory bowel disease who were identified from the Truven Health MarketScan databases. We analyzed data from patients who received 6 months of continuous medical and prescription coverage before and 12 months after their first diagnosis and had no VTE during the 6 months before they first received biologic or corticosteroid therapy. The outcome assessed was any VTE that occurred during the 12-month follow-up period. A multivariate logistic regression model was used to evaluate the effects of biologic, corticosteroid, and combination therapies (biologics and corticosteroids) on VTE risk.
Three hundred twenty-five VTEs occurred during the study period (in 2.25% of patients receiving only corticosteroids, in 0.44% of patients receiving biologics, and in 2.49% of patients receiving combination therapy). Compared with patients receiving only corticosteroids, the odds ratio for VTE in patients receiving only biologics was 0.21 (95% confidence interval, 0.05-0.87) in the multivariate model, and the odds ratio for VTE in patients on combination therapy was 1.01.
Compared with treatment with only a biologic agent, corticosteroid therapy is associated with a nearly 5-fold increase in risk for VTE. Combination therapy with corticosteroids and biologic agents was associated with the same risk for VTE as that of corticosteroids alone. Corticosteroids therefore appear to increase risk for VTE.
A subset of patients with inflammatory bowel diseases (IBD) have continuously active inflammation, leading to a high number of complications and high direct health care costs (diagnostic tests, ...medications, and surgeries) and indirect costs (reduced employment and productivity and fewer opportunities for activities). Identifying these high-risk patients and providing effective interventions could produce better outcomes and reduce costs. We used prior year data to create IBD risk models to predict IBD-related hospitalizations, emergency department visits, and high treatment charges (>$30,000/year) in the subsequent year.
We performed a retrospective study of medical records from all patients with IBD treated at the University of Michigan Hospital from fiscal years 2013-2015. We selected clinical variables from the prior year and tested their abilities to predict 3 adverse outcomes (IBD-related hospitalizations, emergency department visits, and treatment charges >$30,000/year) in the subsequent year. Individual patients were only included once in the data set. We created a multivariate model that was based on a 70% randomly selected cohort (1005 patients) and validated the model on the other 30% (425 patients). Logistic regression was used for bivariate and multivariate analyses.
Factors that predicted high-cost outcomes included the presence of psychiatric illness, use of corticosteroids, use of narcotics, low levels of hemoglobin, and high numbers of IBD-related hospitalizations. In the validation cohort, the model predicted IBD-related hospitalizations, emergency department visits, and high charges in the following year with receiver operating characteristic curve values of 0.751, 0.738, and 0.744, respectively.
We identified 5 factors that can effectively identify patients with IBD at high risk for hospitalization, emergency department visits, and high treatment charges in the next year. These patients should be closely monitored and aggressively managed.
Distinguishing intestinal tuberculosis (ITB) from Crohn's disease (CD) is difficult, although studies have reported clinical, endoscopic, imaging, and laboratory findings that help to differentiate ...these two diseases. We aimed to produce estimates of the predictive power of these findings and construct a comprehensive model to predict the probability of ITB vs. CD.
A systematic literature search for studies differentiating ITB from CD was conducted in MEDLINE, PUBMED, and EMBASE from inception until September 2015. Fifty-five distinct meta-analyses were performed to estimate the odds ratio of each predictive finding. Estimates with a significant difference between CD and ITB and low to moderate heterogeneity (I
<50%) were incorporated into a Bayesian prediction model incorporating the local pretest probability.
Thirty-eight studies comprising 2,117 CD and 1,589 ITB patients were included in the analyses. Findings in the model that significantly favored CD included male gender, hematochezia, perianal disease, intestinal obstruction, and extraintestinal manifestations; endoscopic findings of longitudinal ulcers, cobblestone appearance, luminal stricture, mucosal bridge, and rectal involvement; pathological findings of focally enhanced colitis; and computed tomographic enterography (CTE) findings of asymmetrical wall thickening, intestinal wall stratification, comb sign, and fibrofatty proliferation. Findings that significantly favored ITB included fever, night sweats, lung involvement, and ascites; endoscopic findings of transverse ulcers, patulous ileocecal valve, and cecal involvement; pathological findings of confluent or submucosal granulomas, lymphocyte cuffing, and ulcers lined by histiocytes; a CTE finding of short segmental involvement; and a positive interferon-γ release assay. The model was validated by gender, clinical manifestations, endoscopic, and pathological findings in 49 patients (27 CD, 22 ITB). The sensitivity, specificity, and accuracy for diagnosis of ITB were 90.9%, 92.6%, and 91.8%, respectively.
A Bayesian model based on the meta-analytic results is presented to estimate the probability of ITB and CD calibrated to local prevalence. This model can be applied to patients using a publicly available web application.
Although an additional coronavirus disease 2019 vaccine dose for immunocompromised persons has been recommended in some countries, further data to guide vaccination strategies for patients with ...inflammatory bowel disease (IBD) are urgently needed. We sought to identify factors affecting initial humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with IBD.
In this prospective cohort of SARS-CoV-2 immunized patients with IBD, we evaluated associations between participant age, sex, vaccine type, medication use, and the presence of a detectable antireceptor binding domain antibody and quantitative antibody level.
In total, 1,909 participants were included (1,123, 692, and 94 received BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively) of whom 96% achieved a positive antibody response. On multivariable analysis, factors associated with lack of antibody response were older age (P = 0.043), BNT162b2 vs mRNA-1273 (odds ratio OR 2.1, 95% confidence interval CI 1.0-3.9), and combination therapy with anti-TNF and 6MP, azathioprine, or methotrexate (OR 4.2, 95% CI 2.4-7.3). The use of 5-aminosalicylate or sulfasalazine (OR 0.3, 95% CI 0.1-0.8) and ustekinumab (OR 0.2, 95% CI 0.05-0.8) was associated with decreased odds of lacking antibody response.
Most patients with IBD mount an initial response to SARS-CoV-2 vaccination; however, older patients and those treated with anti-TNF and immunomodulator have blunted responses and may benefit the most from an additional vaccine dose. Patients treated with other classes of immunosuppressive medications have more robust initial immune responses to vaccination. These data should inform key decisions about patient selection for additional coronavirus disease 2019 vaccine doses in patients with IBD.
Background
Infliximab can prevent colectomy in patients hospitalized with acute severe ulcerative colitis (ASUC). In cases of ASUC, fecal losses of infliximab may lead to low drug levels and reduced ...efficacy.
Aim
To determine 90-day colectomy risk and postoperative complications in patients receiving single-dose and accelerated induction of infliximab for ASUC.
Methods
We conducted a retrospective review of patients hospitalized with ASUC requiring infliximab therapy between 2013 and 2017 at the University of Michigan. Patients were excluded if they had an enteric infection, received an anti-TNF previously, or received cyclosporine during the same admission. The primary outcome was colectomy within 90 days of admission. Patients receiving single-dose induction infliximab were compared to those receiving accelerated rescue induction with two doses of infliximab prior to day 14. Administration of accelerated induction was guided by a protocol, suggesting administering a second dose of infliximab to those with only a partial response in CRP 3 days after the initial dose. Postoperative outcomes including 30-day readmission rates and complications were compared using descriptive statistics.
Results
From 2013 to 2017, 66 patients with ASUC met our criteria. Thirty-three received accelerated induction (50.0%). The colectomy rate in the accelerated induction group was 30.3% versus 24.2% in the single-dose induction group (
p
= 0.58). There was no detected difference in postoperative outcomes between the accelerated and single-dose rescue induction.
Conclusions
In this retrospective review, 69.7% of those failing to respond to single-dose infliximab were able to avoid colectomy with an accelerated rescue induction strategy without worsening postoperative outcomes. Larger studies of accelerated dosing infliximab are needed.
Mucosal healing (MH) in inflammatory bowel disease has been associated with improved long-term clinical outcomes. Uncertainty remains as to the magnitude of this effect and to how this association ...changes with time and degree of healing.
PubMed, EMBASE, and Web of Science searches identified 1570 citations. Screening of abstracts identified 155 articles for full-text review, of which 19 met inclusion criteria. For 3 outcomes of interest (surgeries, hospitalizations, remission), weighted random-effects meta-analysis was performed.
In pooled analysis, MH predicted fewer major abdominal surgeries (relative risk RR, 0.34; 95% confidence interval CI, 0.26-0.46), increased remission (RR, 1.84; 95% CI, 1.43-2.36), and fewer hospitalizations (RR, 0.58; 95% CI, 0.42-0.78). Complete MH and partial MH both showed significantly higher rates of favorable outcomes. Separate analyses for Crohn's disease and ulcerative colitis showed identical patterns for surgeries and remission. When subjects with no healing were excluded, and complete versus partial healing was compared, rates of surgery were not significantly different (RR, 0.82; 95% CI, 0.46-1.44). However, complete healing was superior in predicting corticosteroid-free remission (RR, 1.71; 95% CI, 1.24-2.34). Meta-regression found that the predictive power of this complete versus partial healing distinction was strongly associated with the duration of follow-up after endoscopy.
MH is a strong predictor of fewer surgeries, long-term clinical remission, and fewer hospitalizations. Complete healing is not significantly more favorable than partial healing for predicting surgeries or hospitalizations, but it did predict higher rates of clinical remission. This benefit of complete MH over partial healing increases with follow-up time.
Abstract
Background
Inflammatory bowel disease (IBD) is a chronic disease characterized by unpredictable episodes of flares and periods of remission. Tools that accurately predict disease course ...would substantially aid therapeutic decision-making. This study aims to construct a model that accurately predicts the combined end point of outpatient corticosteroid use and hospitalizations as a surrogate for IBD flare.
Methods
Predictors evaluated included age, sex, race, use of corticosteroid-sparing immunosuppressive medications (immunomodulators and/or anti-TNF), longitudinal laboratory data, and number of previous IBD-related hospitalizations and outpatient corticosteroid prescriptions. We constructed models using logistic regression and machine learning methods (random forest RF) to predict the combined end point of hospitalization and/or corticosteroid use for IBD within 6 months.
Results
We identified 20,368 Veterans Health Administration patients with the first (index) IBD diagnosis between 2002 and 2009. Area under the receiver operating characteristic curve (AuROC) for the baseline logistic regression model was 0.68 (95% confidence interval CI, 0.67-0.68). AuROC for the RF longitudinal model was 0.85 (95% CI, 0.84-0.85). AuROC for the RF longitudinal model using previous hospitalization or steroid use was 0.87 (95% CI, 0.87-0.88). The 5 leading independent risk factors for future hospitalization or steroid use were age, mean serum albumin, immunosuppressive medication use, and mean and highest platelet counts. Previous hospitalization and corticosteroid use were highly predictive when included in specified models.
Conclusions
A novel machine learning model substantially improved our ability to predict IBD-related hospitalization and outpatient steroid use. This model could be used at point of care to distinguish patients at high and low risk for disease flare, allowing individualized therapeutic management.
Patients with inflammatory bowel disease(IBD) are frequently exposed to computed tomography (CT). Each CT exposes patients to radiation that cumulatively could increase the risk of malignancy, ...particularly in younger patients. We aim to study the effect of age on CT use in IBD patients seen in the Emergency Department (ED) or the hospital.
We conducted a retrospective cohort study of IBD patients identified in Truven Health Marketscan databases between 2009-2013. The main outcome was use of CT during an ED or inpatient visit. Effect of age on CT use was characterized using logistic regression accounting for important covariables.
There were 66,731 patients with IBD with 144,147 ED or inpatient visits in this cohort with a diagnosis code of IBD. At first visit, 5.8% percent were below age 18. CT was utilized in 26.6% of visits. In multivariable analysis, adjusting for medications, recent surgery, and gender, patients 18-35 were more likely to undergo CT (OR 2.35, 95%CI: 2.20-2.52) compared to those <18. Examining patients only between 16 and 19, the odds of an 18 or 19-year-old undergoing CT is significantly higher than a 16 or 17-year-old (OR 1.96, 95%CI: 1.71-2.24).
Patients with IBD undergo CT more than a quarter of the time in the ED or inpatient setting. Pediatric providers limit radiation exposure among those <18 while adult providers are not as cautious with radiation exposure for the young adult population. Increased awareness of the risks of cumulative radiation exposure in the young adult population is needed.
Tofacitinib is an oral, small molecule inhibitor of JAK for the treatment of ulcerative colitis (UC). We evaluated the onset of symptom improvement in post-hoc analyses of data from 2 phase 3 trials ...of induction therapy with tofacitinib in patients with UC (OCTAVE Induction 1 and 2).
The studies comprised patients with moderate to severe active UC who were intolerant to, or failed by previous treatment with, corticosteroids, thiopurines, and/or tumor necrosis factor (TNF) antagonists. Patients received tofacitinib (10 mg twice daily, n = 905) or placebo (n = 234) for 8 weeks. Daily Mayo stool frequency and rectal bleeding subscores were calculated using diary data from the first 15 days of therapy. We analyzed data from subgroups including failure of prior anti-TNF therapy, baseline corticosteroid use, and baseline serum levels of C-reactive protein.
Mean changes were significantly greater in patients given tofacitinib vs placebo in reductions from baseline stool frequency subscore (tofacitinib: –0.27 vs placebo: –0.11; P < .01), total number of daily bowel movements (–1.06 vs –0.27; P < .0001), and rectal bleeding subscore (–0.30 vs –0.14; P < .01) by day 3. Compared with placebo, more tofacitinib-treated patients had reductions from baseline in stool frequency subscore (by ≥1 point for tofacitinib, 241/837, 28.8% vs placebo, 39/218, 17.9%) (P < .01) and rectal bleeding subscore (by ≥1 point for tofacitinib, 266/830, 32.0% vs placebo, 43/214, 20.1%) (P < .01) by day 3. A consistent effect of tofacitinib was observed in all subgroups.
In a post-hoc analysis of data from phase 3 trials of induction therapy with tofacitinib in patients with UC, we found significant improvements in symptoms among patients given tofacitinib compared with placebo within 3 days. These findings indicate the rapid onset of effect of this drug in patients with UC. ClinicalTrials.gov no: NCT01465763 and NCT01458951.
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