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These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. (ClinicalTrials.gov number, NCT00005094 [ClinicalTrials.gov].).

OBJECTIVES:The objective of this study was to contribute long-term safety data for infliximab and other therapies in Crohn's disease (CD).METHODS:We prospectively evaluated CD patients enrolled in the large, observational Crohn's Therapy, Resource, Evaluation, and Assessment Tool registry, established to compare infliximab safety with conventional nonbiological medications in CD.RESULTS:A total of 6,273 patients were enrolled and evaluated on or before 23 February 2010; 3,420 received infliximab (17,712 patient-years; 89.9% received ≥2 infusions) and 2,853 received other-treatments-only (13,251 patient-years). Mean length of patient follow-up was 5.2 years. More infliximab- than other-treatments-only-treated patients had moderate-to-severe (30.6% vs. 10.7%) or severe-to-fulminant (2.5% vs. 0.6%) disease severity (P<0.001). In the year before enrollment, more infliximab- than other-treatments-only-treated patients required surgical intervention (17.4% vs. 13.6%), medical hospitalization (14.2% vs. 8.8%), prednisone (47.8% vs. 31.4%), immunomodulators (52.0% vs. 32.1%), and narcotic analgesics (17.3% vs. 9.1%). Patient mortality was similar for infliximab- and other-treatments-only-treated patients (0.58 vs. 0.59/100 patient-years). In multivariate logistic regression analyses, treatment with prednisone (hazard ratio (HR)=2.14, 95% confidence interval (CI)=1.55, 2.95; P<0.001) or narcotic analgesics (HR=1.79, 95% CI=1.29, 2.48; P<0.001) and age (HR=1.08, 95% CI=1.07, 1.09; P<0.001) were associated with increased mortality risk. Neither infliximab nor immunomodulator treatment was associated with increased mortality risk. Factors independently associated with serious infections included moderate-to-severe disease activity (HR=2.24, 95% CI=1.57, 3.19; P<0.001), narcotic analgesic treatment (HR=1.98, 95% CI=1.44, 2.73; P<0.001), prednisone therapy (HR=1.57, 95% CI=1.17, 2.10; P=0.002), and infliximab treatment (HR=1.43, 95% CI=1.11, 1.84; P=0.006).CONCLUSIONS:Mortality was similar between infliximab- and other-treatments-only-treated CD patients. An increased risk of serious infection with infliximab was observed, although CD severity and use of prednisone or narcotic analgesics carried higher risks.

No abstract

The Adenoma Prevention with Celecoxib Trial examined the efficacy and safety of the cyclooxygenase (Cox)-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk for colorectal cancer. The trial randomized 2,035 subjects to receive either placebo, celecoxib 200 mg twice daily, or celecoxib 400 mg twice daily. The primary study safety and efficacy analyses involved 3 years of treatment. The results showed significant antitumor effect but also indicated increased cardiovascular adverse events in patients treated with celecoxib compared with placebo. A total of 933 patients participated in an extension of the Adenoma Prevention with Celecoxib Trial, with a planned total treatment and surveillance duration of 5 years. Study medication was stopped early, resulting in a median treatment duration of 3.1 years for those with a year 5 colonoscopy. Patients treated on the placebo arm had a cumulative adenoma incidence of 68.4% over 5 years of observation. This figure was 59.0% (P < 0.0001) for those receiving low-dose celecoxib, and 60.1% (P < 0.0001) for those receiving high-dose celecoxib. The cumulative incidence of advanced adenomas over 5 years was 21.3% of those taking placebo, 12.5% (P < 0.0001) of those taking low dose celecoxib and 15.8% (P < 0.0001) of those taking high-dose celecoxib. Investigator reported treatment emergent adverse events were similar across all treatment groups for categories including renal and hypertensive events and gastrointestinal ulceration and hemorrhage events. For a category composed of cardiovascular and thrombotic events, the risk relative to placebo was 1.6 (95% confidence interval, 1.0, 2.5) for those using 200 mg twice daily celecoxib and 1.9 (95% confidence interval, 1.2, 3.1) for those using 400 mg twice daily celecoxib. Secondary analysis showed an interaction between a baseline history of atherosclerotic heart disease and study drug use with respect to cardiovascular and thrombotic adverse events (P = 0.004). These results confirm the inhibitory effect of celecoxib on colorectal adenoma formation, and provide additional safety data indicating an elevated risk for cardiovascular and thrombotic adverse events, particularly for patients with preexisting atherosclerotic heart disease.