Global Hospitalization Trends for Crohn's Disease and Ulcerative Colitis in the 21st Century: A Systematic Review With Temporal Analyses.

BACKGROUND & AIMS: The evolving epidemiologic patterns of inflammatory bowel disease (IBD) throughout the world, in conjunction with advances in therapeutic treatments, may influence hospitalization rates of IBD. We performed a systematic review with temporal analysis of hospitalization rates for IBD across the world in the 21st century. METHODS: We systematically reviewed Medline and Embase for population-based studies reporting hospitalization rates for IBD, Crohn's disease (CD), or ulcerative colitis (UC) in the 21st century. Log-linear models were used to calculate the average annual percentage change (AAPC) with associated 95% confidence intervals (95% CIs). Random-effects meta-analysis pooled country-level AAPCs. Data were stratified by the epidemiologic stage of a region: compounding prevalence (stage 3) in North America, Western Europe, and Oceania vs acceleration of incidence (stage 2) in Asia, Eastern Europe, and Latin America vs emergence (stage 1) in developing countries. RESULTS: Hospitalization rates for a primary diagnosis of IBD were stable in countries in stage 3 (AAPC, -0.13%; 95% CI, -0.72 to 0.97), CD (AAPC, 0.20%; 95% CI, -1.78 to 2.17), and UC (AAPC, 0.02%; 95% CI, -0.91 to 0.94). In contrast, hospitalization rates for a primary diagnosis were increasing in countries in stage 2 for IBD (AAPC, 4.44%; 95% CI, 2.75 to 6.14), CD (AAPC, 8.34%; 95% CI, 4.38 to 12.29), and UC (AAPC, 3.90; 95% CI, 1.29 to 6.52). No population-based studies were available for developing regions in stage 1 (emergence). CONCLUSIONS: Hospitalization rates for IBD are stabilizing in countries in stage 3, whereas newly industrialized countries in stage 2 have rapidly increasing hospitalization rates, contributing to an increasing burden on global health care systems.

Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn's disease.

BACKGROUND: Biologic therapies in patients with Crohn's disease often yield low clinical and endoscopic remission rates. After multiple failed therapies, combining two biologic therapies is possibly the sole medical alternative to recurrent surgery. However, data on this approach are limited. AIMS: To assess the efficacy and safety of concomitant use of two biologic therapies in the largest cohort to date of refractory Crohn's disease patients. METHODS: Data were extracted from Crohn's disease patients started on dual biologic therapy at two referral centres. Biologics utilised include infliximab, adalimumab, vedolizumab, ustekinumab, certolizumab and golimumab. The primary outcome was endoscopic improvement (>50% reduction in Simplified Endoscopic Score-Crohn's disease [SES-CD] or explicitly stated). Endoscopic remission (SES-CD < 3 or stated), clinical response (Crohn's disease-patient-reported outcome-2 score [PRO2] reduced by 8), clinical remission (PRO2 < 8), and C-reactive protein (CRP) were also assessed. RESULTS: A total of 22 patients with 24 therapeutic trials of dual biologic therapy were identified. The majority of patients had prior surgical resections (91%), stricturing (59%) or penetrating (36%) phenotype, and perianal fistulas (50%). Median number of prior failed biologics was 4. Endoscopic improvement occurred in 43% of trials and 26% achieved endoscopic remission. Fifty per cent had clinical response and 41% achieved clinical remission. There were significant post-treatment reductions in median SES-CD (14.0 [12.0-17.5] to 6.0 [2.5-8.0], P = 0.0005], PRO-2 (24.1 [20.3-27.0] to 13.4 [4.6-21.8], P = 0.002] and CRP (17.0 [11.0-24.0] to 9.0 [4.0-14.0], P = 0.02). Presence of perianal fistulas decreased from 50% to 33%. Adverse events occurred in 13% of trials. CONCLUSION: Dual biologic therapy was associated with clinical, biomarker and endoscopic improvements in selected patients with refractory Crohn's disease who failed multiple biologics. Further studies are needed to validate this approach.

Adverse Events and Nocebo Effects in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIMS: Nocebo effects, adverse outcomes occurring in patients receiving inert therapy, contribute to adverse event [AE] reporting in randomized controlled trials [RCTs]. High placebo AE rates may result in inaccurate estimation of treatment-related AEs. We estimate the pooled rate of AEs in patients randomized to placebo compared to active therapy in inflammatory bowel disease [IBD] RCTs. METHODS: MEDLINE, EMBASE and CENTRAL were searched to March 1, 2017 for RCTs of conventional medical therapies for Crohn's disease [CD] or ulcerative colitis [UC]. Rates of AEs, serious AEs [SAEs], AE-related trial withdrawal, infections and worsening IBD were pooled using a random-effects model. RESULTS: We included 124 CD [n = 26 042] and 71 UC RCTs [n = 16 798]. The pooled placebo AE rate was 70.6% (95% confidence interval [CI]: 65.3%, 75.4%) and 54.5% [47.8%, 61.1%] in CD and UC RCTs, respectively. There was no significant risk difference [RD] in AE, SAE or AE-related withdrawal rates between CD patients receiving placebo or active drug. A 1.6% [95% CI: 0.1%, 3.1%] increase in AE rates was observed among UC patients randomized to active therapy. Patients receiving active therapy had a higher risk of infection (RD 1.0% [95% CI: 0.4%, 1.7%] for CD, 2.9% [95% CI: 1.4%, 4.4%] for UC) although a lower risk of worsening CD (RD -3.2% [95% CI: -4.8%, -1.5%]) or UC (RD -3.7% [95% CI: -5.7%, -1.8%]). CONCLUSIONS: AEs are commonly reported by patients randomized to either placebo or active treatment in IBD RCTs. Clinically relevant differences in AE, SAE and AE-related withdrawal were not observed.

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.