Association of Anti-Tumor Necrosis Factor Therapy With Mortality Among Veterans With Inflammatory Bowel Disease.

Importance: Inflammatory bowel disease (IBD) is commonly treated with corticosteroids and anti-tumor necrosis factor (TNF) drugs; however, medications have well-described adverse effects. Prior work suggests that anti-TNF therapy may reduce all-cause mortality compared with prolonged corticosteroid use among Medicare and Medicaid beneficiaries with IBD. Objective: To examine the association between use of anti-TNF or corticosteroids and all-cause mortality in a national cohort of veterans with IBD. Design, Setting, and Participants: This cohort study used a well-established Veteran's Health Administration cohort of 2997 patients with IBD treated with prolonged corticosteroids (≥3000-mg prednisone equivalent and/or ≥600 mg of budesonide within a 12-month period) and/or new anti-TNF therapy from January 1, 2006, to October 1, 2015. Data were analyzed between July 1, 2019, and December 31, 2020. Exposures: Use of corticosteroids or anti-TNF. Main Outcomes and Measures: The primary end point was all-cause mortality as defined by the Veterans Health Administration vital status file. Marginal structural modeling was used to compare associations between anti-TNF therapy or corticosteroid use and all-cause mortality. Results: A total of 2997 patients (2725 men [90.9%]; mean [SD] age, 50.0 [17.4] years) were included in the final analysis, 1734 (57.9%) with Crohn disease (CD) and 1263 (42.1%) with ulcerative colitis (UC). All-cause mortality was 8.5% (n = 256) over a mean (SD) of 3.9 (2.3) years' follow-up. At cohort entry, 1836 patients were new anti-TNF therapy users, and 1161 were prolonged corticosteroid users. Anti-TNF therapy use was associated with a lower likelihood of mortality for CD (odds ratio [OR], 0.54; 95% CI, 0.31-0.93) but not for UC (OR, 0.33; 95% CI, 0.10-1.10). In a sensitivity analysis adjusting prolonged corticosteroid users to include patients receiving corticosteroids within 90 to 270 days after initiation of anti-TNF therapy, the OR for UC was statistically significant, at 0.33 (95% CI, 0.13-0.84), and the OR for CD was 0.55 (95% CI, 0.33-0.92). Conclusions and Relevance: This study suggests that anti-TNF therapy may be associated with reduced mortality compared with long-term corticosteroid use among veterans with CD, and potentially among those with UC.

Selecting End Points for Disease-Modification Trials in Inflammatory Bowel Disease: the SPIRIT Consensus From the IOIBD.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), are chronic and disabling disorders. Prospective disease-modification trials to prevent disease progression are eagerly awaited. However, disease progression is not clearly defined. The objective of the Selecting End PoInts foR Disease-ModIfication Trials (SPIRIT) initiative was to achieve international expert consensus on the endpoints to be used in future IBD-disease modification trials. METHODS: This initiative under the auspices of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) began with a systematic literature search to evaluate the current evidence on the definition of disease progression in IBD. On October 22, 2019, a consensus meeting took place during the United European Gastroenterology Week (UEGW) Congress in Barcelona, during which predefined proposed statements were discussed in a plenary session and voted on anonymously. Agreement was defined as at least 75% of participants voting for any one statement. RESULTS: The group agreed that the ultimate therapeutic goal in both CD and UC is to prevent disease impact on patient's life (health-related quality of life, disability, fecal incontinence), midterm complications (encompass bowel damage in CD, IBD-related surgery and hospitalizations, disease extension in UC, extraintestinal manifestations, permanent stoma, short bowel syndrome), and long-term complications (gastrointestinal and extraintestinal dysplasia or cancer, mortality). CONCLUSIONS: Recommendations on which goals to achieve in disease-modification trials for preventing disease progression in patients with IBD are proposed by the SPIRIT consensus. However, these recommendations will require validation in actual clinical studies before implementation in disease-modification trials.

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.

The development of extraintestinal manifestation and related risk factors in Crohn's patients.

BACKGROUND: Crohn's disease (CD) primarily involves gastrointestinal tract; however, it can present with extraintestinal manifestations (EIMs), which leads to significant morbidity. Frequency of EIMs and associated risk factors vary due to genetic and environmental differences in studies. AIM: To examine the frequency and risk factors associated with EIMs in CD. METHOD: Patients with CD under follow-up from March 1986 to October 2011 were included in this study. Demographics, type of EIMs, autoimmune diseases, and clinical features of CD were recorded. Frequency of EIMs and associated risk factors were analyzed. RESULTS: Three hundred thirty-six patients with CD were included in the study (mean follow-up duration 7.54 years). 55.4% (n: 186) were male and the mean age at diagnosis of CD was 30.6 years (range, 10.3-68.2 years). At least one EIM was detected in 47.3% and multiple EIMs in 22.9% of the cohort. Oral, joint, and skin involvements (32.4%, 24.7%, 9.2%, respectively) were the most common EIMs. Female gender (OR: 2.19, 95% CI: 1.34-3.58, p = 0.001), corticosteroid usage (OR: 2.32, 95% CI: 1.28-4.22, p = 0.007), and positive family history (OR: 5.61, 95% CI: 1.95-3.58, p = 0.001) were independent risk factors for EIM development. Colonic involvement (OR: 3.93, 95% CI: 1.59-9.68, p = 0.003), no surgical operation (OR: 2.31, 95% CI: 1.14-4.68, p = 0.020), and corticosteroid usage (OR: 2.85, 95% CI: 1.07-7.61, p = 0.037) were independent risk factors for multiple EIM development. CONCLUSION: Although the immunological and clinical associations between EIMs and CD cannot be fully elucidated, identifying specific relationships of immune-mediated diseases will help to better understand CD pathogenesis.

A propensity score weighted comparison of vedolizumab and adalimumab in Crohn's disease.

BACKGROUND AND AIM: There are no head-to-head randomized controlled trials between biologics in Crohn's disease (CD). We aimed to perform a multicenter, real-life comparison of the effectiveness of vedolizumab (VDZ) and adalimumab (ADA) in CD. METHODS: Data of consecutive patients with CD treated with VDZ and ADA from January 2016 to April 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. The effectiveness was evaluated at 12, 52 weeks, and as failure-free survival at the end of follow up. Propensity score analysis was performed using the inverse probability of treatment weighting method. RESULTS: Five hundred eighty-five treatments (VDZ: n = 277; ADA: n = 308) were included (median follow-up: 56.0 weeks). After 12 weeks, a clinical response was achieved in 64.3% patients treated with VDZ and in 83.1% patients treated with ADA (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.38-1.10, P = 0.107), while at 52 weeks, a clinical response was observed in 54.0% patients treated with VDZ and in 69.1% patients treated with ADA (OR 0.77, 95% CI 0.45-1.31, P = 0.336). Cox survival analysis weighted for propensity score showed no significant difference in the probability of failure-free survival between the two drugs (hazard ratio = 1.20, 95% CI 0.83-1.74, P = 0.340). Post-treatment endoscopic response and mucosal healing rates were similar between the two groups (endoscopic response: 35.3% for VDZ and 25.5% for ADA, P = 0.15; mucosal healing: 31.8% for VDZ and 33.8% for ADA, P = 0.85). CONCLUSIONS: In the first study comparing VDZ and ADA in CD via propensity score analysis, the drugs showed comparable effectiveness and a similar safety profile.

Systemic Chemotherapy for Metastatic Colitis-Associated Cancer Has a Worse Outcome Than Sporadic Colorectal Cancer: Matched Case Cohort Analysis.

BACKGROUND: Colitis-associated cancers (CAC) are a catastrophic complication of inflammatory bowel disease; at diagnosis, CAC is frequently at an advanced stage. Although the genomic alterations (GA) in CAC are different from sporadic colorectal cancer (CRC), the same systemic therapies are used. We compared clinically relevant outcomes using standard care systemic chemotherapy of stage IV CAC versus a matched patient control cohort of stage IV CRC patients. PATIENTS AND METHODS: A retrospective matched cohort design was used. Eighteen cases of stage IV CAC (7 ulcerative colitis, 11 Crohn disease) and 18 CRC were identified. GA analysis was available for all patients. Outcome endpoints included response rate and response duration, progression-free survival, and OS. RESULTS: Although the response rates were similar (CAC 35.7% vs. CRC 57.1%, P = .45), the median duration of response for CAC was significantly shorter (1.4 months, vs. CRC 11.8 months, P = .006). There was no difference in dose density of first-line therapy between cohorts, suggesting that shorter response duration was due to more rapid development of chemotherapy resistance. Median OS was significantly shorter for CAC patients (13 vs. 27.6 months, P = .034). As expected, there was a difference in the spectrum of GA between CAC and CRC cohorts. However, GA associated with poor prognosis (eg, B-Raf) were no more frequent in the CAC cohort. CONCLUSION: Clinically meaningful outcomes of duration of response and OS are worse for CAC versus sporadic CRC patients treated with FOLFOX or FOLFIRI as first therapy for metastatic disease.

Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents.

BACKGROUND AND AIM: Biological therapies may be changing the natural history of inflammatory bowel diseases (IBDs), reducing the need for surgical intervention. We aimed to assess whether the availability of anti-TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: Retrospective, cohort study of patients diagnosed within a 6-year period before and after the licensing of anti-TNFs (1990-1995 and 2007-2012 for CD; 1995-2000 and 2007-2012 for UC) were identified in the ENEIDA Registry. Surgery-free survival curves were compared between cohorts. RESULTS: A total of 7370 CD patients (2022 in Cohort 1 and 5348 in Cohort 2) and 8069 UC patients (2938 in Cohort 1 and 5131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post-biological cohorts. The cumulative probability of surgery was lower in CD following anti-TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3, and 5 years, respectively P < 0.0001), although not in UC (3% and 2%, 4% and 4%, and 6% and 5% at 1, 3, and 5 years, respectively; P = 0.2). Ileal involvement, older age at diagnosis and active smoking in CD, and extensive disease in UC, were independent risk factors for surgery, whereas high-volume IBD centers (in both CD and UC) and immunosuppressant use (in CD) were protective factors. CONCLUSIONS: Anti-TNF availability was associated with a reduction in early surgery for CD (driven mainly by earlier and more widespread immunosuppressant use) but not in UC.

Surgery for Crohn's disease during pregnancy: A nationwide survey.

BACKGROUND AND AIMS: Crohn's disease (CD) frequently affects young women and may require surgery during pregnancy. Data regarding operation for CD in expectant mothers are scare. MATERIALS AND METHODS: This was a retrospective nationwide survey from the GETAID Chirurgie. Any woman with CD undergoing surgery during pregnancy was eligible. RESULTS: A total of 15 cases were collected between 1992 and 2015. Most operations were performed due to penetrating or stricturing complications. Mean gestational age at delivery was 34 weeks, with a mean birth weight of 2507 g. Maternal post-operative complications occurred in two-thirds of cases. Maternal mortality rate was 6.7% and neonatal mortality rate 9.1%. CONCLUSIONS: This is the largest case series of surgery for CD during pregnancy. This operation may have significant morbidity and mortality for mother, fetus, and newborn. Indication needs to be tailored to maternal status, disease severity, and gestational age. Surgery should be managed by experienced gynecologists, physicians, and surgeons. Active CD may be associated with a greater risk to the fetus than the surgical procedure itself.

The reproducibility of skeletal muscle signal intensity on routine magnetic resonance imaging in Crohn's disease.

BACKGROUND AND AIM: Myosteatosis is a prognostic factor in cancer and liver cirrhosis. It can be determined noninvasively using computed tomography or, as shown recently, by magnetic resonance (MR) imaging. The primary aim was to analyze the reproducibility of skeletal muscle signal intensity on routine MR-enterographies, as indicator of myosteatosis, in Crohn's disease (CD) and to explore the association between skeletal muscle signal intensity at diagnosis with time to intestinal resection. METHODS: CD patients undergoing MR-enterography within 6 months from diagnosis and having a maximum of 5 years follow-up were included. Skeletal muscle signal intensity was analyzed on T1-weighted fat-saturated post-contrast images. Intra-observer and inter-observer reproducibilities were assessed by intra-class correlation coefficient and Cohen's kappa. Intra-observer and inter-observer variabilities were determined by Pearson correlation coefficient and displayed by Bland-Altman plots. Time to intestinal resection was studied by Kaplan-Meier analysis. RESULTS: Median time between diagnosis and MR-enterography was 5 weeks (inter-quartile range 1-9) in 35 CD patients. Skeletal muscle signal intensity showed good intra-class correlation and substantial agreement (for intra-observer, intraclass correlation coefficient = 0.948, κ = 0.677; and inter-observer reproducibility, intraclass correlation coefficient = 0.858, κ = 0.622). Resection free survival was shorter in the low skeletal muscle signal intensity group (P = 0.037). CONCLUSION: Skeletal muscle signal intensity on routine MR-enterographies is reproducible and was associated with unfavorable disease outcome, indicating potential clinical relevance.

Thromboembolic events in inflammatory bowel disease.

GOAL OF THE STUDY: Inflammatory bowel disease (IBD) is associated with an increased risk of thromboembolic events (TEE) during outbreaks, increasing morbidity and mortality. The aim of our study was to specify the prevalence of TEE in IBD patients and to determine their epidemiological, clinical and evolutionary characteristics. MATERIEL AND METHODS: This is a retrospective study collecting all patients with IBD, who had a thromboembolic complication confirmed by imagery, between January 2012 and December 2018. RESULTS: One hundred patients with IBD were diagnosed during the study period. A TEE occurred in 6 patients (5.9%). These patients had an average age of 41 years, divided into 4 women and 2 men. Five patients had Crohn's disease and one patient had ulcerative colitis. The IBD was active in all patients. Five patients were already hospitalized and under preventive heparin therapy. Patients had deep venous thrombosis of the lower limbs in 3 cases, associated with pulmonary embolism in 1 case, cerebral venous thrombosis in 2 cases and pulmonary embolism isolated in 1 case. Thrombophilia investigations were negative in all patients. Evolution under medical treatment was favorable in 4 patients and fatal in 2 patients. CONCLUSION: In our study, the prevalence of TEE in patients with IBD was 5.9%. Thrombosis occurred during the active phase of IBD in all cases.

Presentation and Management of Arterial Thromboembolisms during Active Inflammatory Bowel Disease: Case Series and Literature Review.

BACKGROUND: Active inflammatory bowel disease (IBD) is associated with considerable risk for thromboembolism; however, arterial thromboembolism is rare and associated with considerable morbidity and mortality. Their management requires careful coordination between multiple providers, and as a consequence, much of the published literature is limited to case reports published across specialties. METHODS: We examined our recent institutional experience with aortoiliac, mesenteric, and peripheral arterial thromboembolisms in patients with either Crohn's disease or ulcerative colitis. To supplement our experience, a comprehensive literature review was performed using MEDLINE and EMBASE databases from 1966 to 2019. Patient demographics, flare/thromboembolism management, and outcomes were abstracted from the selected articles and our case series. RESULTS: Fifty-two patients with IBD, who developed an arterial thromboembolism, were identified (49 from published literature and 3 from our institution). More than 82% of patients presented during an active IBD flare. Surgical intervention was attempted in 77% of patients, which included open thromboembolectomy, catheter-directed thrombolysis, or bowel resection. Thromboembolism resolution was achieved in 76% of patients with comparable outcomes with either catheter-directed thrombolysis or open thrombectomy (83.3% vs. 68.2%). Nearly one-third of patients underwent small bowel resection or colectomy. In 2 patients, thromboembolism resolution was achieved only after total abdominal colectomy for severe pancolitis. Multiple thromboembolectomies were associated with higher risk for amputation. Overall mortality was 11.5% but was greatest for occlusive aortoiliac and mesenteric thromboembolism (14.3% and 57%, respectively). All survivors of occlusive superior mesenteric artery thromboembolism suffered short gut syndrome requiring small bowel transplant. CONCLUSIONS: Patients with IBD, who develop an arterial thromboembolism, can expect overall poor outcomes. Catheter-directed thrombolysis achieved comparable outcomes with open thromboembolectomy without undue bleeding risk. Total abdominal colectomy for moderate-to-severe pancolitis is an emerging strategy in the management of refractory arterial thromboembolism. Successful surgical management may include open thromboembolectomy, catheter-directed thrombolysis, and bowel resection when indicated.

Inflammatory Bowel Disease: A Nationwide Study of Hip Fracture and Mortality Risk After Hip Fracture.

BACKGROUND AND AIMS: With rising rates of inflammatory bowel diseases [IBD] in older adults, management of comorbidities such as osteoporosis is becoming increasingly important. Hip fracture [HF] is the most serious consequence of low bone mineral quality and is associated with excess risk of mortality. For older IBD patients, there are only limited data available. Therefore, we aimed to assess the association of IBD with HF, and all-cause mortality risk after HF, among IBD patients older than 50 years. METHODS: In a national database-registered case-control study, 56 821 HF cases aged ≥50 years, and 113 718 age-, sex- and region-matched non-hip-fracture controls, were analysed between 2012 and 2016. A history of IBD was assessed from data from Austrian social health insurance funds. Logistic regression and Cox proportional multivariate models were used to test the association of IBD with HF and post-hip fracture mortality risk. RESULTS: A total of 531 patients were identified with IBD (25.0% men, mean age 81.2 years, standard deviation [SD] 9.7). Analysis, adjusted for anti-osteoporotic treatment, use of glucocorticoids, and selected medications, showed that IBD patients had an increased odds of HF (odds ratio [[OR] 2.22, 95% confidence interval [CI] 1.86-2.64). Patients with Crohn's disease [CD] revealed a higher HF odds in contrast to patients with ulcerative colitis [OR 2.91, 95% CI 2.17-3.89 and OR 1.89, 95% CI 1.52-2.35, respectively]. Overall mortality risk after HF was higher among female CD patients [HR 1.75, 95% CI 1.28-2.41] than in the general population. CONCLUSIONS: IBD was strongly associated with HF in older patients. Post-hip fracture mortality risk was elevated particularly in women with CD.

Small Bowel Adenocarcinoma: Is There a Difference in Survival for Crohn's Versus Sporadic Cases?

BACKGROUND AND AIMS: It is well known that Crohn's disease is a risk factor for the development of small bowel adenocarcinoma. However, the association between Crohn's disease-associated small bowel adenocarcinoma and survival is less understood. The goal of this study was to determine the impact of Crohn's disease on survival in small bowel adenocarcinoma. METHODS: Patients with small bowel adenocarcinoma, either associated with Crohn's disease or diagnosed sporadic, were identified in the National Cancer Database from 2004-2016. The primary outcome was overall survival. RESULTS: Of 2668 patients, 493 had Crohn's disease-associated small bowel adenocarcinoma and 2175 had sporadic small bowel adenocarcinoma. Crohn's disease patients were more likely to present at a younger age [62 vs 65, p < 0.001], have tumours located in the ileum [62.7% vs 25.0%, p < 0.001], and have poorly differentiated tumours [47.0% vs 31.7%, p < 0.001] compared with sporadic small bowel adenocarcinoma. Factors associated with significantly decreased survival included older age (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.02-1.03, p < 0.00)], higher Charlson score [HR: 1.39, 95% CI: 1.13-1.72, p = 0.002], higher tumour grade [HR: 1.09, 95% CI: 1.04-1.14, p < 0.001], positive surgical margins [HR: 1.60, 95% CI: 1.39-1.84, p < 0.001], and higher stage of disease [HR: 1.90, 3.75, 8.13, 95% CI: 1.37-2.64, 2.68-5.24, 5.77-11.47, for II, III, IV, respectively, compared with I, all p < 0.001]. Receipt of chemotherapy was associated with significantly improved survival [HR: 0.61, 95% CI: 0.53-0.70, p < 0.001]. Crohn's disease [HR: 1.01, 95% CI: 0.99-1.02, p = 0.39], was not significantly associated with survival. CONCLUSION: Compared with sporadic patients, Crohn's disease patients have similar overall survival, and Crohn's disease is not an independent risk factor for mortality.

Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964-2014.

OBJECTIVES: To examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years. DESIGN: Swedish nationwide register-based cohort study 1964-2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873. RESULTS: During 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn's disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002-2014 had 2.3 years shorter mean estimated life span than matched comparators. CONCLUSIONS: Adult-onset and elderly-onset patients with UC, Crohn's disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.

Trends and risk factors of mortality analysis in patients with inflammatory bowel disease: a Taiwanese nationwide population-based study.

BACKGROUND: Inflammatory bowel disease (IBD) was emerging as a worldwide epidemic disease, and the advanced therapy changed the clinical course and possibly the outcomes. Our previous study reported a higher mortality rate from (IBD) in Taiwan than in Western countries. We proposed to analyze the trend and risk factors of mortality in order to improve the care quality of IBD patients. METHODS: This retrospective study was conducted to analyze data for January 2001 to December 2015 from a registered database, compiled by the Taiwan's National Health Insurance. RESULTS: Between 2001 and 2015, a total of 3806 IBD patients [Crohn's disease (CD): 919; ulcerative colitis (UC): 2887] were registered as having catastrophic illness, and 8.2% of these patients died during follow-up. The standardized mortality ratios (SMRs) of CD and UC were 3.72 (95% CI 3.02-4.55) and 1.44 (95% CI 1.26-1.65), respectively, from 2001 to 2015, respectively. A comparison of the periods of 2011-2015 and 2001-2005 revealed a decrease in the mortality rates from both UC and CD. Multivariate Cox proportional hazards analysis identified elderly individuals; sepsis and pneumonia were the risk factors for IBD mortality. The specific risk factors of mortality were liver cancer for UC and surgeries for CD. CONCLUSION: For further decreasing IBD-related mortality in Taiwan, we need to pay special attention toward elderly individuals, infection control, cancer screening and improvement in perioperative care.

Risk factors associated with progression to intestinal complications of Crohn disease.

BACKGROUND: Crohn disease is a chronic bowel disease that causes serious complications. Prevalence of Crohn disease is increasing. Studies have shown that the behavior of the disease is not stable and severe complications secondary to behavior change over time have been shown. In this study, we aimed to evaluate the prognostic risk factors associated with phenotypic change in Crohn disease in a Turkish patient cohort. METHODS: Patients followed up from March 1986 to August 2011 were evaluated for demographic and clinical characteristics to determine possible risk factors and initial clinical phenotype of the disease based on the Montreal classification. The cumulative probabilities of developing stricturing or penetrating intestinal complications were estimated using the Kaplan-Meier analysis. Univariate and multivariate Cox-proportional hazard models were used to assess associations between baseline clinical characteristics and intestinal complications. RESULTS: Three hundred and thirty patients (mean age, 30.6 ±â€Š11.1 years; 148 female) were included in the study. Mean follow-up duration was 7.4 ±â€Š5.3 years (range: 1.0-25.0 years). At baseline 273 patients had inflammatory-type disease, 57 patients experienced stricturing/penetrating intestinal complications before or at the time of diagnosis. The cumulative probability of developing complicated disease was 37.4% at 5 years, 54.3% at 10 years, 78.8% at 25 years. Independent predictors associated with progression to intestinal complications were current smoking, perianal disease, extra-intestinal manifestations, and location of disease. CONCLUSIONS: Location of disease is the most powerful indicator for the development of stenosis and penetrating complications in inflammatory-type disease. Patients with ileal involvement should be considered for more aggressive immunosuppressive therapy.

Long-term safety of certolizumab pegol in rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis, psoriasis and Crohn's disease: a pooled analysis of 11 317 patients across clinical trials.

Objective: To review long-term certolizumab pegol (CZP) safety across all approved indications: rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), psoriasis (PSO) and Crohn's disease (CD). Methods: Data were pooled across 49 UCB-sponsored CZP clinical trials (27 RA, one axSpA, one PsA, five PSO, 15 CD) to August 2017. Serious adverse events (SAEs) of interest (infections, malignancies, autoimmunity/hypersensitivity events, major adverse cardiovascular events (MACE), gastrointestinal (GI) perforations, psoriasis events, laboratory abnormalities) and deaths were medically reviewed by an external expert committee, using predefined case rules. Incidence rates (IRs)/100 patient-years (PY) are presented by indication; standardised mortality and malignancy rates were calculated using WHO/GLOBOCAN/SEER databases. Pregnancies with maternal CZP exposure are also reported. Results: Of 11 317 CZP-treated patients across indications (21 695 PY CZP exposure; maximum: 7.8 years), infections were the most common SAEs (overall IR: 3.62/100 PY; IRs ranged from 1.50/100 PY(PSO) to 5.97/100 PY(CD)). The IR for malignancies was 0.82/100 PY, including lymphoma (0.06/100 PY). MACE and GI perforation IRs in CZP-treated patients were 0.47/100 PY and 0.08/100 PY and were highest in RA and CD, respectively. Patients with PSO had the lowest SAE rates. The incidence of deaths and malignancies aligned with expected general population data. Conclusion: This extensive overview of the CZP safety profile in clinical trials, across all indications, provides large-scale confirmation of previous reports. No new safety signals or relevant non-disease-related laboratory abnormalities were identified. The study demonstrated some indication-specific differences in certain SAE rates that may be attributable to the underlying inflammatory disease.

Hospitalization Outcomes for Inflammatory Bowel Disease in Teaching vs Nonteaching Hospitals.

BACKGROUND: Hospitalizations contribute significantly to the annual health care expenditure for inflammatory bowel disease (IBD), and reducing cost of care without compromising outcomes is a rising priority. Teaching hospitals (THs) have higher costs and utilize trainees in care to a greater extent than community hospitals, and it is unknown how hospital teaching status (HTS) affects outcomes. We therefore sought to investigate the impact of HTS on IBD hospitalization outcomes. METHODS: We used the Vizient clinical database to identify patients hospitalized between October 1, 2014, and March 31, 2018, for IBD. Vizient hospitals were divided into major THs, minor THs, and non-THs. We used multivariable linear regression of aggregated discharge data to assess the association of HTS with mean length of stay (LOS), mean direct cost (DC), 30-day readmission rate (RR), and in-hospital mortality rate (MR), while adjusting for demographics and disease complexity. RESULTS: Vizient included 29,863 discharges among 291 hospitals for ulcerative colitis (UC) and 62,698 discharges among 314 hospitals for Crohn's disease (CD) between October 1, 2014, and March 31, 2018. Unadjusted mean LOS, mean DC, and 30-day RR were greater among THs for both UC and CD. Unadjusted MR was greater among major THs for UC but not CD. After multivariable analysis, only 30-day RR for UC was increased in major THs relative to non-THs (1.98%; 95% confidence interval, 0.33%-3.61%). CONCLUSIONS: Differences in metrics of cost-effective hospital care for patients with IBD appear to be driven by disease severity rather than HTS. Future research should attempt to better characterize factors driving resource utilization for IBD hospitalizations.

Mortality Risk of Inflammatory Bowel Disease: A Case-Control Study of New York State Death Records.

BACKGROUND: Studies examining the mortality risk of inflammatory bowel disease (IBD) have yielded conflicting results, and most do not account for recent advancements made in the treatment of Crohn's disease (CD) and ulcerative colitis (UC). We aim to assess the overall, premature, and cause-specific mortality in IBD patients over a 17-year time period and to evaluate any differences since the introduction of biologic therapy. METHODS: A death record case-control study was performed to explore the odds of premature death (before age 65) and all-cause mortality among those with IBD. Cases consisted of IBD patients (1,129 with CD and 841 with UC) who died in New York State (NYS) from 1993 to 2010. Controls (n = 7880) were matched 4:1 on the basis of sex and zip code from those who died in NYS in the same time frame, without an IBD diagnosis. RESULTS: Compared with matched controls, those with CD (OR 1.56, CI 95% 1.34-1.82), but not UC (OR 0.72, CI 95% 0.59-0.89), were more likely to die prematurely. Both those with UC and CD were more likely to die from a gastrointestinal cause (CD OR 15.28, 95% CI 12.11-19.27; UC OR 14.02, 95% CI 10.76-18.26). There was no difference in the cause or age of death before and after the introduction of anti-TNF agents in those with IBD. CONCLUSIONS: Both CD and UC cases were more likely to die of a gastrointestinal etiology, and CD patients were more likely to die prematurely. There was no significant difference in the premature death, average age of death, and cause of death in this IBD population after the availability of anti-TNF therapy.