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

Abstract

Sajesh K Veettil,1 Surakit Nathisuwan,2 Siew Mooi Ching,3–5 Peerawat Jinatongthai,6,7 Kean Ghee Lim,8 Siang Tong Kew,9 Nathorn Chaiyakunapruk7,10–12 1Department of Pharmacy Practice, School of Pharmacy, International Medical University, Kuala Lumpur, Malaysia; 2Clinical Pharmacy Division, Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 3Department of Family Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia; 4Malaysian Research Institute on Ageing, Universiti Putra Malaysia, Serdang, Malaysia; 5Department of Medical Sciences, School of Healthcare and Medical Sciences, Sunway University, Selangor, Malaysia; 6Division of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Ubon Ratchathani University, Ubon Ratchathani, Thailand; 7School of Pharmacy, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia; 8Department of Surgery, Clinical School, International Medical University, Seremban, Malaysia; 9Department of Internal Medicine, School of Medicine, International Medical University, Kuala Lumpur, Malaysia; 10Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Center of Pharmaceutical Outcomes Research, Naresuan University, Phitsanulok, Thailand; 11School of Pharmacy, University of Wisconsin, Madison, WI, USA; 12Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Selangor, Malaysia 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. Keywords: colorectal cancer, colorectal adenomas, chemoprevention, celecoxib, meta-analysis, randomized controlled trials, risk–benefit integrated analyses

Keywords

• Colorectal cancer
• colorectal adenomas
• chemoprevention
• celecoxib
• meta-analysis
• randomized controlled trials
• risk-benefit integrated analyses.