Systematic review with meta-analysis: use of 5-aminosalicylates and risk of colorectal neoplasia in patients with inflammatory bowel disease

Background: The relationship of 5-aminosalicylates' use with the risk of colorectal neoplasia in patients with inflammatory bowel disease (IBD) has been the focus of a growing body of research.

Aim: To investigate this association through an updated meta-analysis of observational studies.

Methods: PubMed, Scopus and major conference proceedings were searched up to December 2016. The identified studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates were calculated using random-effect models. Detailed subgroup analyses were performed. The GRADE approach was used to assess the quality of evidence.

Results: Thirty-one independent observational studies including 2137 cases of colorectal neoplasia (of which 76% were cancers) were incorporated. Between-study heterogeneity was moderate, while strong suspicion of small-study effects was raised. The overall analysis revealed a protective association between 5-aminosalicylates' use and colorectal neoplasia (RR = 0.57, 95% CI: 0.45-0.71). When the analysis was stratified according to study design and setting, the association was significant in cohort (RR = 0.65, 95% CI: 0.43-0.99; n = 10) and case-control studies (RR = 0.53, 95% CI: 0.40-0.70; n = 21), population-based (RR = 0.70, 95% CI: 0.52-0.94; n = 12) and hospital-based studies (RR = 0.46, 95% CI: 0.34-0.61; n = 19). Exposure to 5-aminosalicylates was protective against cancer (RR = 0.58, 95% CI: 0.45-0.74) and dysplasia (RR = 0.54, 95% CI: 0.35-0.84). The reduction in colorectal neoplasia risk was strong in ulcerative colitis (RR = 0.50, 95% CI: 0.38-0.64), but nonsignificant in Crohn's disease (RR = 0.76, 95% CI: 0.43-1.33). Mesalazine (mesalamine) use was protective (RR = 0.70, 95% CI: 0.51-0.94) with evidence of a dose-effect. The effect of sulfasalazine was marginally nonsignificant (RR = 0.72, 95% CI: 0.51-1.01).

Conclusions: Our findings support a potential chemopreventive role of 5-aminosalicylates in IBD. Further, high-quality prospective research is warranted.