Economic Burden of Fatigue in Inflammatory Bowel Disease.

Background: This retrospective study gathered medical/pharmacy claims data on patients with inflammatory bowel disease (IBD) between January 01, 2000 and March 31, 2019 from the IBM MarketScan commercial claims database to assess the real-world impact of fatigue on healthcare costs in patients newly diagnosed with IBD. Methods: Eligible participants were ≥18 years, newly diagnosed with IBD (≥2 separate claims), and had ≥12 months of continuous database enrollment before and after fatigue diagnosis. The date of fatigue diagnosis was the index date; participants were followed for 12 months post-index. Patients with (cases) or without (controls) fatigue were matched 1:1 by propensity score matching. Patients with evidence of prior IBD diagnosis/treatment, or those with a chronic disease other than IBD wherein fatigue is the primary symptom, were excluded. Healthcare resource utilization (HCRU), including hospitalizations, inpatient and outpatient visits, and associated costs were compared between cases and controls. Results: Matched IBD cohorts (21 321 cases/21 321 controls) were identified (42% Crohn's disease [CD] and 58% ulcerative colitis [UC]) with similar baseline characteristics (average age: 46 years; 60% female). Cases versus controls had significantly more all-cause outpatient visits (incidence rate ratio [IRR], 95% confidence intervals [95% CI]: 1.64 [1.61, 1.67], P < .001) and all-cause hospitalizations (IRR [95% CI]: 1.92 [1.81, 2.04], P < .001); as well as significantly higher all-cause total direct healthcare costs (mean: $24 620 vs. $15 324; P < .001). Similar findings were observed for IBD-related outcomes, as well as in CD- and UC-specific subgroups. Conclusions: Presence of fatigue is associated with an increase in HCRU and total medical costs among patients newly diagnosed with IBD.

Content Validity and Psychometric Evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in Patients with Crohn's Disease and Ulcerative Colitis.

BACKGROUND: Patients with Crohn's disease (CD) or ulcerative colitis (UC) frequently experience fatigue, although it is often overlooked in medical research and practice. AIMS: To explore patients' experience of fatigue and evaluate content validity, psychometric properties, and score interpretability of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in patients with CD or UC. METHODS: Concept elicitation and cognitive interviews were conducted with participants aged ≥ 15 years with moderately-to-severely active CD (N = 30) or UC (N = 33). To evaluate psychometric properties (reliability and construct validity) and interpretation of FACIT-Fatigue scores, data from two clinical trials were analyzed [ADVANCE (CD): N = 850; U-ACHIEVE (UC): 248]. Meaningful within-person change was estimated using anchor-based methods. RESULTS: Almost all interview participants reported experiencing fatigue. Over 30 unique fatigue-related impacts were reported per condition. The FACIT-Fatigue was interpretable for most patients. FACIT-Fatigue items had good internal consistency (Cronbach's α 0.86-0.88 for CD and 0.94-0.96 for UC); the total score displayed acceptable test-retest reliability (intraclass correlation coefficients > 0.60 for CD and > 0.90 for UC). FACIT-Fatigue scores had acceptable convergent validity with similar measures. A 7-10 point improvement for CD and 4-9 point improvement for UC on the FACIT-Fatigue total score may represent meaningful improvements. CONCLUSIONS: These results highlight the importance of fatigue among adolescents and adults with CD or UC and provide evidence that the FACIT-Fatigue is content valid and produces reliable, valid, and interpretable scores in these populations. Care should be taken if using the questionnaire with adolescents who may be less familiar with the word "fatigue." Clinical trial registration numbers NCT03105128 (date of registration: 4 April 2017) and NCT02819635 (date of registration: 28 June 2016).

The cost of inflammatory bowel disease in high-income settings: a Lancet Gastroenterology & Hepatology Commission.

The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.

Assessment of Safety and Efficacy of Tofacitinib, Stratified by Age, in Patients from the Ulcerative Colitis Clinical Program.

BACKGROUND: In patients with ulcerative colitis (UC), risks of infection and malignancies increase with age. Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. This analysis assessed age as a risk factor for adverse events of special interest (AESI) in the tofacitinib UC clinical program. METHODS: Data were from phase 2 and 3 induction studies, a phase 3 maintenance study, and an open-label, long-term extension study. Efficacy and/or safety outcomes were analyzed in the Induction, Maintenance, and Overall Cohorts (patients who received ≥ 1 dose of tofacitinib), stratified by age. The effects of baseline demographic and disease-related factors on AESI incidence were assessed by Cox proportional-hazards regression analysis. RESULTS: In the Overall Cohort (1157 patients with ≤ 6.8 years' tofacitinib treatment), age was a statistically significant predictor of herpes zoster (HZ), malignancies excluding nonmelanoma skin cancer (NMSC), and NMSC. Other statistically significant predictors included prior tumor necrosis factor inhibitor failure for HZ, NMSC, and opportunistic infection events, and prior duration of UC for malignancies excluding NMSC. In the Induction and Maintenance Cohorts, a higher proportion of tofacitinib-treated than placebo-treated patients (numerical difference) achieved the efficacy endpoints (endoscopic improvement, clinical remission, clinical response) across all age groups. CONCLUSIONS: Older individuals receiving tofacitinib as induction and maintenance therapy to treat UC may have an increased risk of HZ, malignancies (excluding NMSC), and NMSC versus similarly treated younger patients, consistent with findings from the general population. Across all age groups, tofacitinib demonstrated greater efficacy than placebo as an induction and maintenance therapy. CLINICALTRIALS.GOV REGISTRATION NUMBERS: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612.

Age was assessed as a risk factor for adverse events of special interest in the tofacitinib ulcerative colitis clinical program. Older individuals receiving tofacitinib may have an increased risk of herpes zoster, malignancies (excluding nonmelanoma skin cancer), and nonmelanoma skin cancer versus similarly treated younger patients.

Evaluating cost per remission and cost of serious adverse events of advanced therapies for ulcerative colitis.

BACKGROUND: Determining the relative cost-effectiveness between advanced therapeutic options for ulcerative colitis (UC) may optimize resource utilization. We evaluated total cost per response, cost per remission, and cost of safety events for patients with moderately-to-severely active UC after 52 weeks of treatment with advanced therapies at standard dosing. METHODS: An analytic model was developed to estimate costs from the US healthcare system perspective associated with achieving efficacy outcomes and managing safety outcomes for advanced therapies approved for the treatment of UC. Numbers needed to treat (NNT) for response and remission, and numbers needed to harm (NNH) for serious adverse events (SAEs) and serious infections (SIs) were derived from a network meta-analysis of pivotal trials. NNT for induction and maintenance were combined with drug regimen costs to calculate cost per clinical remission. Cost of managing AEs was calculated using NNH for safety outcomes and published costs of treating respective AEs. RESULTS: Costs per remission were $205,240, $249,417, $267,463, $365,050, $579,622, $750,200, and $787,998 for tofacitinib 10 mg, tofacitinib 5 mg, infliximab, vedolizumab, golimumab, adalimumab, and ustekinumab, respectively. Incremental costs of SAEs and SIs collectively were $136,390, $90,333, $31,888, $31,061, $20,049, $12,059, and $0 for tofacitinib 5 mg, golimumab, adalimumab, tofacitinib 10 mg, infliximab, ustekinumab, and vedolizumab (reference), respectively. CONCLUSIONS: Tofacitinib was associated with the lowest cost per response and cost per remission, while vedolizumab had the lowest costs related to SAEs and SIs. Balancing efficacy versus safety is important when evaluating the costs associated with treatment of moderate-to-severe UC.

The Global Incidence of Peptic Ulcer Disease Is Decreasing Since the Turn of the 21st Century: A Study of the Organisation for Economic Co-Operation and Development (OECD).

INTRODUCTION: Peptic ulcer disease (PUD) is a common cause of hospitalization worldwide. We assessed temporal trends in hospitalization for PUD in 36 Organisation for Economic Co-operation and Development (OECD) countries since the turn of the 21st century. METHODS: The OECD database contains data on PUD-related hospital discharges and mortality for 36 countries between 2000 and 2019. Hospitalization rates for PUD were expressed as annual rates per 100,000 persons. Joinpoint regression models were used to calculate the average annual percent change (AAPC) with 95% confidence intervals (CIs) for each country, which were pooled using meta-analyses. The incidence of PUD was forecasted to 2021 using autoregressive integrated moving average and Poisson regression models. RESULTS: The overall median hospitalization rate was 42.4 with an interquartile range of 29.7-60.6 per 100,000 person-years. On average, hospitalization rates (AAPC = -3.9%; 95% CI: -4.4, -3.3) and morality rates (AAPC = -4.7%; 95% CI: -5.6, -3.8) for PUD have decreased from 2000 to 2019 globally. The forecasted incidence of PUD hospitalizations in 2021 ranged from 3.5 per 100,000 in Mexico to 92.1 per 100,000 in Lithuania. Across 36 countries in the OECD, 329,000 people are estimated to be hospitalized for PUD in 2021. DISCUSSION: PUD remains an important cause of hospitalization worldwide. Reassuringly, hospitalizations and mortality for PUD have consistently been falling in OECD countries in North America, Latin America, Europe, Asia, and Oceania. Identifying underlying factors driving these trends is essential to sustaining this downward momentum.

Inflammatory Bowel Disease Does Not Impact Mortality but Increases Length of Hospitalization in Patients with Acute Myocardial Infarction.

BACKGROUND AND AIM: Inflammatory bowel diseases (IBD) have been associated with increased risk of cardiovascular events. We aimed to investigate the outcomes of myocardial infarction (MI) in patients with IBD. METHODS: We performed a cross-sectional study utilizing data from the Nationwide Inpatient Sample from the years 1998 to 2010. ICD-9-CM codes were used to identify patients with Crohn's disease (CD) (555.X), ulcerative colitis (UC) (556.X), and acute MI (410.X). Outcomes in patients with MI with and without IBD were compared. Univariate analysis was performed. Multivariate logistic regression was used to determine the effect of UC and CD on in-hospital MI mortality after adjusting for confounders. RESULTS: A total of 2,629,161 MI, 3,607 UC and 3784 CD patients were analyzed. UC (odds ratio [OR], 1.12; 95% CI 0.98-1.29) and CD (OR 0.99; 95% CI 0.86-1.15) did not affect in-hospital mortality in patients with MI. There was no difference between in-hospital mortality in patients with MI with or without UC (7.75% vs. 7.05%; p = 0.25) or in patients with MI with or without CD (6.50% vs. 6.59%; p = 0.87). The length of stay (LOS) was higher in IBD patients and total charges were statistically higher in patients with UC as compared to non-IBD patients ($65,182 vs. $53,542; p < 0.001). CONCLUSIONS: This study shows that IBD does not impact in-hospital mortality from MI. However, patients with MI with IBD have longer LOS. Patients with UC have higher total hospitalization charges than patients with MI without IBD. Further prospective studies are needed to assess the outcomes of MI in IBD patients.

Certolizumab Trough Levels and Antibodies in Crohn Disease: A Single-Center Experience.

Background: Certolizumab pegol (CZP) has been successfully used for the treatment of Crohn disease (CD); however, real-world data regarding the utility of CZP trough levels (CTLs) are lacking. We aimed to correlate CTL with CD outcomes and to determine frequency of CZP antibodies. Methods: Retrospective evaluation of all CD patients on maintenance CZP with CTL obtained between 2016 and 2019. Outcomes included: median CTL, presence of anti-CZP antibodies, biochemical response (BR), clinical response (CR), radiologic response (RR), radiologic healing (RH), and mucosal healing (MH). Results: Seventy-seven CD patients were included. Median CTL was 18.9 µg/mL (interquartile range, 7.6-35.4). Twenty-three patients (27.3%) had positive antibody levels, with lower median CTL compared to patients with no antibodies (0.0 vs 29.8; P < 0.0001). Median CTL levels were higher in patients with vs without CR (30.4 vs 10.3 µg/mL; P = 0.0015) and RR (29.6 vs 5.8 µg/mL; P = 0.006). CZP dosing at least every 2 weeks was associated with higher odds of achieving MH (odds ratio, 3.2; 95% confidence interval, 1.03-9.97). CTL resulted in change in clinical management in 62.7% of cases and presence of CMZ antibodies was associated with an odds ratio of 5.83 (95% confidence interval, 1.57-21.73) of change in management. Receiver operating characteristic curve and quartile analysis suggested that CTL >19 µg/mL is associated with increased rates of CR and RR. Conclusions: Higher CTL was significantly associated with CR and RR. The rate of CZP antibodies was 27.3%. Our data suggest maintenance CTL of ≥19 µg/mL should be achieved in order to optimize outcomes in clinical practice.

Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates from the Ulcerative Colitis Clinical Programme.

BACKGROUND AND AIMS: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes. METHODS: Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event]. RESULTS: In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23-7.00] for placebo and 1.35 [0.16-4.87] and 0.64 [0.02-3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02-5.42], 2.05 [0.42-6.00], and 6.64 [3.19-12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24-2.27], 3.48 [2.79-4.30], and 0.15 [0.04-0.38], respectively. No SIs resulted in death. CONCLUSIONS: During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.

Effects of Race and Ethnicity on Diagnosis and Management of Inflammatory Bowel Diseases.

Although Crohn's disease (CD) and ulcerative colitis (UC) have been considered as disorders that affect individuals of European ancestry, the epidemiology of the inflammatory bowel diseases (IBDs) is changing. Coupled with the increasing incidence of IBD in previously low-incidence areas, the population demographics of IBD in the United States are also changing, with increases among non-White races and ethnicities. It is therefore important to fully understand the epidemiology and progression of IBD in different racial and ethnic groups, and the effects of race and ethnicity on access to care, use of resources, and disease-related outcomes. We review differences in IBD development and progression among patients of different races and ethnicities, discussing the effects of factors such as access to care, delays in diagnosis, and health and disease perception on disparities in IBD care and outcomes. We identify research priorities for improving health equity among minority patients with IBD.

Clinical Trials for Inflammatory Bowel Disease: Global Guidance During the COVID-19 Pandemic.

The severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]-causing coronavirus disease [COVID]-19 pandemic poses major challenges for patients with inflammatory bowel disease [IBD] to be recruited and maintained in clinical trials. However, clinical trials offer patients who have failed multiple drugs access to study medications with alternative modes of action and the potential for relief from inflammation-mediated symptoms. Therefore, the continuation of clinical trials in IBD during the COVID-19 pandemic is important both for participants and for the community of IBD patients, due to the dire need for an expanded therapeutic armamentarium. As the safety of patients in clinical trials is the leading principle, we are providing ten specific rules to guide patients and principal investigators safely through the challenging time.

Trends in hospitalisation rates for inflammatory bowel disease in western versus newly industrialised countries: a population-based study of countries in the Organisation for Economic Co-operation and Development.

BACKGROUND: Hospitalisation rates for inflammatory bowel disease (IBD) vary across the world. We aimed to investigate temporal patterns of hospitalisation for IBD in member countries of the Organisation for Economic Co-operation and Development (OECD). METHODS: From the OECD database, we assessed IBD-related hospitalisation rates (expressed as annual rates per 100 000 inhabitants) for 34 countries from 1990 to 2016. We calculated mean hospitalisation rates for the period 2010-15 and used joinpoint regression models to calculate average annual percentage changes with 95% CIs. FINDINGS: Mean hospitalisation rates for IBD from 2010 to 2015 were highest in North America (eg, 33·9 per 100 000 in the USA), Europe (eg, 72·9 per 100 000 in Austria), and Oceania (eg, 31·5 per 100 000 in Australia). Hospitalisation rates for IBD were stabilising or decreasing over time in many countries in these regions but increasing in others. Countries in Asia and Latin America and the Caribbean had the lowest IBD-related hospitalisation rates but the greatest increases in rates over time. For example, Turkey had an annual hospitalisation rate of 10·8 per 100 000 inhabitants and an average annual percentage change of 10·4% (95% CI 5·2-15·9). Similarly, Chile had an annual hospitalisation rate of 9·0 per 100 000 inhabitants and an average annual percentage change of 5·9% (4·9-7·0). INTERPRETATION: Hospitalisation rates for IBD are high in western countries but are typically stabilising or decreasing, whereas rates in many newly industrialised countries are rapidly increasing, which reflects the known increase in IBD prevalence in these countries. Potential explanations for these trends include changes in the epidemiology of IBD, health-care delivery, and infrastructure in these countries, as well as overall country-specific patterns in hospitalisations and differences between countries in data collection methods. FUNDING: None.

Vedolizumab Drug Level Correlation With Clinical Remission, Biomarker Normalization, and Mucosal Healing in Inflammatory Bowel Disease.

BACKGROUND/AIMS: The clinical utility of vedolizumab (VDZ) trough levels (VTLs) in inflammatory bowel disease (IBD) is not well defined. The aims of this study are to determine the median VTLs and frequency of detected antibodies, the correlation of VTLs with C-reactive protein (CRP) and mucosal healing (MH), and the change in clinical management based on VTLs. METHODS: A cross-sectional study of IBD patients treated with VDZ with VTLs checked between July 1, 2016, and March 1, 2017, was conducted. Mucosal healing was defined as absence of mucosal ulcers in Crohn's disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC). Normal CRP was defined as ≤8 mg/L. RESULTS: A total of 171 patients (62% CD, 31% UC, 7% indeterminate colitis) were included. Median VTLs was 15.3 ug/mL (range, 0-60), and 1 patient had detectable antibodies to VDZ. Patients with a normal CRP had a median VTLs of 17.3 ug/mL vs 10.7 ug/mL in high CRP patients (P = 0.046). This was noted in CD (20.3 vs 10.4 ug/mL; P = 0.005) but not in UC patients (14.4 vs 20.8; P = 0.72). Mucosal healing was achieved in 35% of patients (37 of 105); among these, median VTLs was 13.7 ug/mL vs 16.1 ug/mL in patients who did not achieve MH (P = 0.64). Vedolizumab trough levels resulted in a change in clinical management in 73%. CONCLUSIONS: Our cohort showed a low rate of immunogenicity to VDZ and an association between VTLs and CRP in CD but not in UC patients. No relationship between VTLs and MH was detected. Vedolizumab trough level measurements altered management in approximately three fourths of patients.

Clinical Benefit of Capsule Endoscopy in Crohn's Disease: Impact on Patient Management and Prevalence of Proximal Small Bowel Involvement.

Background: Ileocolonoscopy and computed tomography (CT) or magnetic resonance (MR) enterography (CTE/MRE) are utilized to evaluate patients with small bowel (SB) Crohn's disease (CD). The purpose of our study was to estimate the impact of capsule endoscopy (CE) on patient management after clinical assessment, ileocolonoscopy, and CTE/MRE. Methods: We prospectively analyzed 50 adult CD patients without strictures at clinically indicated ileocolonoscopy and CTE/MRE exams. Providers completed pre- and post-CE clinical management questionnaires. Pre-CE questionnaire assessed likelihood of active SBCD and management plan using a 5-point level of confidence (LOC) scales. Post-CE questionnaire assessed alteration in management plans and contribution of CE findings to these changes. A change of ≥2 on LOC scale was considered clinically meaningful. Results: Of the 50 patients evaluated (60% females), median age was 38 years, median disease duration was 3 years, and median Crohn's Disease Activity Index (CDAI) score was 238 points. All CTE/MRE studies were negative for proximal disease. CE detected proximal disease in 14 patients (28%) with a median Lewis score of 215 points. CE findings altered management in 17 cases (34%). The most frequent provider-perceived benefits of CE were addition of new medication (29%) and exclusion of active SB mucosal disease (24%). Conclusion: CE is a safe imaging modality that alters clinical management in patients with established SBCD by adding incremental information not available at ileocolonoscopy and cross-sectional enterography.

Rate and Predictors of Interval Esophageal and Gastric Cancers after Esophagogastroduodenoscopy in the United States.

BACKGROUND AND AIMS: In the United States, little is known about the rates of interval upper gastrointestinal (GI) cancer (possibly missed out) after an esophagogastroduodenoscopy (EGD) is performed. Data from non-US studies reported interval cancer rates of 7-26%. We aimed to study the rate and predictors of interval upper GI cancers in the United States. METHODS: Using the random 5% sample of Medicare beneficiaries in the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified patients diagnosed with esophageal or gastric cancer during 2000-2007. EGD performed within 36 months prior to cancer diagnosis was identified using CPT codes. Cancers diagnosed 6-36 months after EGD were defined as interval (vs. detected) cancers. The chi-square test and the multivariate logistic model were used in statistical analysis. RESULTS: Of 751 patients diagnosed with upper GI cancer, 52 patients (6.9%) were diagnosed with interval cancers 6-36 months after EGD. The rate of interval cancers was 5.5% (31/568) for gastroenterologists and 11.5% (21/183) for non-gastroenterologists (p < 0.01). In multivariate logistic regression, EGDs performed by gastroenterologists (vs. non-gastroenterologists: OR 0.46, 95% CI 0.25-0.83) and those in inpatient setting (vs. outpatient: OR 0.53, 95% CI 0.28-0.997) were associated with a lower likelihood of interval cancers. Sensitivity analyses limited to outpatient EGDs or interval cancers 6-30 months after EGDs led to similar results. CONCLUSIONS: The rate of interval cancers after EGD is the same as the rate of colonoscopy among Medicare patients in the United States. EGDs performed by gastroenterologists and in in-patient settings were associated with a lesser likelihood of interval cancers.

Radiological Response Is Associated With Better Long-Term Outcomes and Is a Potential Treatment Target in Patients With Small Bowel Crohn's Disease.

OBJECTIVES: Crohn's disease (CD) management targets mucosal healing on ileocolonoscopy as a treatment goal. We hypothesized that radiologic response is also associated with better long-term outcomes. METHODS: Small bowel CD patients between 1 January 2002 and 31 October 2014 were identified. All patients had pre-therapy computed tomography enterography (CTE)/magnetic resonance enterography (MRE) with follow-up CTE or MRE after 6 months, or 2 CTE/MREs≥6 months apart while on maintenance therapy. Radiologists characterized inflammation in up to five small bowel lesions per patient. At second CTE/MRE, complete responders had all improved lesions, non-responders had worsening or new lesions, and partial responders had other scenarios. CD-related outcomes of corticosteroid usage, hospitalization, and surgery were assessed using Kaplan-Meier survival analysis and multivariable Cox models. RESULTS: CD patients (n=150), with a median disease duration of 9 years, had 223 inflamed small bowel segments (76 with strictures and 62 with penetrating, non-perianal disease), 49% having ileal distribution. Fifty-five patients (37%) were complete radiologic responders, 39 partial (26%), and 56 non-responders (37%). In multivariable Cox models, complete and partial response decreased risk for steroid usage by over 50% (hazard ratio (HR)s: 0.37 (95% confidence interval (CI), 0.21-0.64); 0.45 (95% CI, 0.26-0.79)), and complete response decreased the risk of subsequent hospitalizations and surgery by over two-thirds (HRs: HR, 0.28 (95% CI, 0.15-0.50); HR, 0.34 (95% CI, 0.18-0.63)). CONCLUSIONS: Radiological response to medical therapy is associated with significant reductions in long-term risk of hospitalization, surgery, or corticosteroid usage among small bowel CD patients. These findings suggest the significance of radiological response as a treatment target.

Decreased Risk of Colorectal Cancer after Colonoscopy in Patients 76-85 Years Old in the United States.

BACKGROUND/AIMS: The benefits of colonoscopy in reducing colorectal cancer (CRC) risk for patients over 75 years are controversial. We aimed to determine whether colonoscopy use is associated with a decreased risk of CRC in patients 76-85 years old in the United States (US). PATIENTS AND METHODS: All patients in the Medicare 5% random sample of the Surveillance, Epidemiology and End Results-Medicare linked database 76-85 years old at outpatient colonoscopy between January 1, 1998 and December 31, 2002 were identified. Using the Kaplan-Meier method, we estimated the cumulative incidence of CRC in the above-mentioned colonoscopy group and compared with the control group of patients without colonoscopy. All patients were followed until diagnosis of CRC or carcinoma in situ, death or December 31, 2005. The multivariate Cox proportional hazards model was used in statistical analysis. CRC was separated by location into distal vs. proximal CRC in subgroup analysis. RESULTS: Of 5,701 patients in the colonoscopy group, 37 (0.65%) patients were diagnosed with CRC, compared to 379 (1.55%) out of 24,437 patients in the control group (p < 0.001). The cumulative incidences of distal and proximal CRC were lower in the colonoscopy group compared to those in the control group (5-year distal CRC: 0.26 vs. 0.77%; 5-year proximal CRC: 0.43 vs. 0.79%, both p < 0.05). In multivariate Cox regression, colonoscopy was associated with decreased risk of all CRC (hazard ratio ((HR) 0.42, 95% CI 0.28-0.65), distal CRC (HR 0.36, 95% CI 0.18-0.70), and proximal CRC (HR 0.53, 95% CI 0.30-0.92)). CONCLUSION: Among patients 76-85 years old in the United States, colonoscopy use was associated with decreased risks of both distal and proximal CRC, with a smaller risk reduction in distal colon. Due to inherent limitations associated with our retrospective design, future prospective studies are needed to validate these findings.

Epidemiology, risk factors and management of cardiovascular diseases in IBD.

IBD is an established risk factor for venous thromboembolism. In the past few years, studies have suggested that patients with IBD might also be at an increased risk of coronary heart disease and stroke. The increased risk is thought to be similar to the level of risk seen in patients with other chronic systemic inflammatory diseases such as rheumatoid arthritis. The risk of developing these conditions is particularly increased in young adults with IBD, and more so in women than in men. Conventional cardiovascular risk factors are not over-represented in patients with IBD, so the increased risk could be attributable to inflammation-mediated atherosclerosis. Patients with IBD often have premature atherosclerosis and have biochemical and genetic markers similar to those seen in patients with atherosclerotic cardiovascular disease. The role of chronic inflammation in IBD-associated cardiovascular disease merits further evaluation. Particular attention should be given to the increased risk observed during periods of increased disease activity and potential modification of the risk by immunosuppressive and biologic therapies for IBD that can modify the disease activity. In addition, preclinical studies suggest that cardiovascular medications such as statins and angiotensin-converting enzyme inhibitors might also favourably modify IBD disease activity, which warrants further evaluation.