Efficacy and safety of celecoxib on the incidence of recurrent colorectal adenomas: a systematic review and meta-analysis

Abstract

Background: Celecoxib has previously been shown to be effective in reducing recurrent colorectal adenomas, but its long-term effects are unknown. In addition, safety issues are of major concern. Therefore, we examined the efficacy and safety of celecoxib as a chemopreventive agent along with its posttreatment effect. Methods: We performed a meta-analysis based on a systematic review of randomized controlled trials (RCTs) comparing celecoxib at various doses (400 mg once daily, 200 mg twice daily, and 400 mg twice daily) vs placebo in persons with history of colorectal adenomas. Several databases were searched from inception up to April 2018. Long-term follow-ups of RCTs were also included to evaluate posttreatment effect. Primary outcome was the incidence of recurrent colorectal adenomas. Various safety outcomes were evaluated, especially cardiovascular (CV) events. Risk-benefit integrated analyses were also performed. Results: A total of three RCTs (4,420 patients) and three post-trial studies (2,159 patients) were included in the analysis. Use of celecoxib at any dose for 1-3 years significantly reduced the incidence of recurrent advanced adenomas (risk ratio, 0.42 [95% CI, 0.34-0.53]) and any adenomas (0.67 [95% CI, 0.62-0.72]) compared with placebo. Subgroup analysis on different dosing suggested a greater effect with 400 mg twice daily. However, celecoxib 400 mg twice daily significantly increased the risk of serious adverse (1.2 [95% CI, 1.0-1.5]) and CV events (3.42 [95% CI, 1.56-7.46]), while celecoxib at 400 mg/day, especially with once daily dosing, did not increase CV risk (1.01 [95% CI, 0.70-1.46]). Analysis of post-trial studies indicated that the treatment effect disappeared (1.15 [95% CI, 0.88-1.49]) after discontinuing celecoxib for >2 years. Conclusion: Celecoxib 400 mg once daily dosing could potentially be considered as a viable chemopreventive option in patients with high risk of adenomas but with low CV risk. Long-term trials on celecoxib at a dose of ≤400 mg either once or twice daily are warranted.

Cytokinesis-block micronucleus assay of celecoxib and celecoxib derivatives

“…Celecoxib was suggested as chemopreventive agent [ 24 ]. For this application, side effects like cardiovascular events have to be considered, but also gastrointestinal adverse effects like gastroduodenal ulcerations may occur after prolonged application, although celecoxib showed a lower incidence than diclofenac or ibuprofen [ 25 ].…”

“…COX-2 is considered to be a main target for chemopreventive action, therefore selective COX-2 inhibitors like celecoxib are promising substances, as their selectivity reduces the probability of adverse effects related to COX-1 inhibition [ 27 ]. Celecoxib is under investigation for chemoprevention of colorectal adenomas and long-term studies showed a clear reduction of recurrent adenomas – but higher doses (400 mg twice daily) pose the risk of severe cardiovascular effects making correct dosing crucial for the outcome of the treatment [ 24 ]. In addition, celecoxib could be beneficial in radiotherapy by preventing normal tissue to get damaged and sensitise tumour cells to radiation [ 28 ].…”

Very-low-dose aspirin and surveillance colonoscopy is cost-effective in secondary prevention of colorectal cancer in individuals with advanced adenomas: network meta-analysis and cost-effectiveness analysis

“…Celecoxib is the most effective CPA, but the CV adverse events are of great concern. Moreover, the protective effect of celecoxib does not persist after its withdrawal [ 7 ]. The risk–benefit profile favours the use of ASAVLD, especially for those with a history of ACAs.…”

“…In addition, the CPA should be ideally free from adverse events but also cost-effective considering its long-term use. There are several candidates, including aspirin and celecoxib but it is unknown if these agents fullfill all the requirements described above [ 6 , 7 ]. The US Preventive Services Task Force (USPSTF) guideline supports the use of very-low-dose aspirin (ASAVLD, ≤ 100 mg/day) for primary chemoprevention of CRC [ 8 ] but secondary chemoprevention in particular patients with a previous history of ACAs is unclear.…”

Network Pharmacology and Molecular Docking on the Molecular Mechanism of Luo-hua-zi-zhu (LHZZ) Granule in the Prevention and Treatment of Bowel Precancerous Lesions

“…Endoscopic excision has become the main treatment of CRA, however, removal of CRA cannot effectively reduce the recurrence ( Nishihara et al, 2013 ). At present, folic acid, metformin, aspirin, celecoxib and other anti-proliferation and anti-inflammatory treatment are applied in clinic as anti-CRA drugs, but the effect is not satisfactory ( Liu et al, 2017 ; Passarelli et al, 2018 ; Veettil et al, 2019 ). Therefore, it is urgent to understand the pathogenesis of CRA and find safe and effective drugs.…”