Celecoxib for the prevention of sporadic colorectal adenomas
Monica M Bertagnolli1, Craig J Eagle, Ann G Zauber
1Brigham and Women's Hospital, Boston, USA. mbertagnolli@partners.org
Background:
Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia.
Methods:
We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test.
Results:
Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P<0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P<0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9).
Conclusions:
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].).
Insights
Celecoxib effectively prevents colorectal adenomas by inhibiting cyclooxygenase-2 (COX-2). However, increased cardiovascular risks mean it cannot be routinely recommended for this purpose.
Area of Science:
- Gastroenterology
- Oncology
- Pharmacology
Background:
- Cyclooxygenase-2 (COX-2) inhibitors show promise in preventing colorectal neoplasia.
- Evidence suggests COX-2 inhibitors may prevent sporadic colorectal tumors.
Purpose of the Study:
- To evaluate the efficacy of celecoxib in preventing colorectal adenomas.
- To assess the safety and efficacy of different celecoxib dosages.
Main Methods:
- Randomized trial involving patients with prior adenoma removal.
- Patients received placebo, 200 mg, or 400 mg celecoxib twice daily.
- Follow-up colonoscopies at one and three years to detect new adenomas.
Main Results:
- Celecoxib significantly reduced the incidence of colorectal adenomas at three years.
- The 400 mg dose showed a 45% reduction (RR 0.55) and the 200 mg dose a 33% reduction (RR 0.67).
- Celecoxib use was associated with an increased risk of cardiovascular events.
Conclusions:
- Celecoxib is effective in preventing colorectal adenomas.
- Routine recommendation is limited due to increased cardiovascular event risk.
- Further research is needed to balance benefits and risks.
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