Epidemiology, clinical characteristics, evolution and treatments in newly diagnosed inflammatory bowel disease (IBD): results from the nationwide EpidemIBD study of GETECCU

Background: Updated data on the incidence, evolution and treatment strategies used in IBD management in South Europe is needed. This is the largest study on the recent epidemiology of IBD in Spain. The aims of this study were (i) to assess the incidence of IBD in Spain; (ii) to describe the main epidemiological and clinical characteristics of patients at diagnosis and the evolution of the disease; and (iii) to explore the use of treatments in the biological era. Methods: Prospective and population-based nationwide registry. Adult patients diagnosed with IBD Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)- during 2017 in the 17 Spanish regions were included and will be followed-up for 5 years after diagnosis. Treatment was grouped into 5 categories: mesalazine (oral or topical), steroids (intravenous, oral or topical), immunomodulators (thiopurines, methotrexate or cyclosporine), biologics (anti-TNF, vedolizumab or ustekinumab) and surgery. Cumulative incidence of exposure to each of the studied treatments was estimated by Kaplan–Meier curves. Results: In total, 3627 incident cases of IBD diagnosed during 2017 from 111 centres covering over 23 millions of adult inhabitants (about 50% of the Spanish population) comprise the study cohort. The overall incidence (per 100000 person-years) of IBD was 14.3: 6.5 for CD, 7.1 for UC, and 0.7 for IBD-U . During a median follow-up of 10 months, 33 (2.4%) CD patients progressed to a more severe phenotype, and 2 (0.01%) UC patients to more extensive involvement. Conclusions: The incidence of IBD in Spain is relatively high and similar to figures reported in Northern Europe. IBD patients require the use of substantial diagnostic and therapeutic resources, which are higher in CD than in CU. One third of patients are hospitalised in the first year after diagnosis and over 5% undergo surgery. Our results highlight the high burden of IBD as well as the important challenges faced by healthcare systems to manage this costly and complex disease

Cardiovascular events associated with rofecoxib : final analysis of the APPROVe trial

Background: Selective inhibition of cyclo-oxygenase-2 has been associated with an increased risk of cardiovascular events in several clinical trials. The Adenomatous Polyp Prevention on Vioxx (APPROVe) study assessed the effect of 3-year treatment with a cyclo-oxygenase-2 inhibitor, rofecoxib (25 mg), on recurrence of neoplastic polyps of the large bowel. We report the cardiovascular outcomes of a long-term follow-up of participants in the trial. Methods: The APPROVe study is a multicentre, randomised, placebo-controlled, double-blind trial. 2587 patients with a history of colorectal adenomas were recruited at 108 centres worldwide during 2000 and 2001. Participants were followed for adverse events while on treatment and during the following 14 days. However, after early termination of treatment because of cardiovascular toxicity, we attempted to follow up all randomised patients for at least 1 year after stopping study treatment. External committees blindly assessed potential serious cardiovascular events. The focus of the analysis was the combined incidence of non-fatal myocardial infarction, non-fatal stroke, and death from cardiovascular, haemorrhagic, and unknown causes (Antiplatelet Trialists' Collaboration [APTC] combined endpoint). We used Cox proportional hazards regression to calculate endpoint hazard ratios. The study is registered with ClinicalTrials.gov, number NCT0282386. Findings: We obtained extended post-treatment cardiovascular follow-up data from 84% of participants, and extended mortality follow-up from 95%. In total, 59 individuals had an APTC endpoint in the rofecoxib group and 34 in the placebo group (hazard ratio 1.79, 95% CI 1.17-2.73; p=0.006). In the first year after cessation of treatment, there was a non-significant increase in the risks of APTC endpoints. The APTC hazard ratio did not substantially change over time. Interpretation: Use of rofecoxib is associated with increased rates of APTC events. Study data are compatible with an early increase in risk that persists for one year after stopping treatment

Ezetimibe added to statin therapy after acute coronary syndromes

BACKGROUND: Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter (1.3 to 3.2 mmol per liter) if they were not receiving lipid-lowering therapy. The combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin-ezetimibe) was compared with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization ( 6530 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study was 53.7 mg per deciliter (1.4 mmol per liter) in the simvastatin-ezetimibe group, as compared with 69.5 mg per deciliter (1.8 mmol per liter) in the simvastatin-monotherapy group (P<0.001). The Kaplan-Meier event rate for the primary end point at 7 years was 32.7% in the simvastatin-ezetimibe group, as compared with 34.7% in the simvastatin-monotherapy group (absolute risk difference, 2.0 percentage points; hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). Rates of pre-specified muscle, gallbladder, and hepatic adverse effects and cancer were similar in the two groups. CONCLUSIONS: When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit