Coxib Safety in Patients with Inflammatory Bowel Diseases: A Meta-analysis

Abstract

Background: Patients with inflammatory bowel diseases (IBD) frequently have extraintestinal manifestations including arthritis, sacroiliitis, and ankylosing spondylitis. While the treatment of these rheumatological conditions with traditional non-steroidal anti-inflammatory drugs (NSAIDs) has been reported to lead to frequent IBD exacerbation, the safety of cyclooxygenase-2 (COX-2) inhibitors (Coxibs) remains unclear. Objectives: Our aim is to carry out a meta-analysis to verify if Coxibs, employed to treat rheumatological manifestations, are associated with an increased risk of exacerbation of IBD compared to placebo. Study Design and Setting: A MEDLINE, SCOPUS, ISI-Web of Knowledge, and EMBASE search of all studies published in English from 1965 to April 15, 2015, was conducted. Articles on the safety of Coxibs in patients with IBD were identified using the terms “Coxibs or cyclooxygenase-2 inhibitors or COX-2 inhibitors AND inflammatory bowel disease.” Methods: The criteria of exclusion of the studies were NSAIDs administration within 2 weeks before starting Coxibs. For the “proportion” meta-analysis, the studies had to report the proportion of patients that had to discontinue the Coxibs therapy due to an exacerbation of IBD; for the “relative risk” meta-analysis, the studies had to be prospective with a comparison between patients taking Coxibs and patients taking placebo. Two authors independently reviewed titles and abstracts of references retrieved from the literature search and selected potentially relevant studies. Differences in opinion were resolved by discussion until consensus was reached. If an agreement failed to be reached, a third author was consulted. The quality of each study was assessed on a 5-point scale adapted from studies by the Quebec Task Force on Whiplash-Associated disorders and Jadad. Results: The search identified 72 publications of which 7 studies reported the proportion of patients with IBD that had to stop the Coxibs therapy because of a worsening of the activity of IBD. The pooled proportion of flare up of IBD in patients that received Coxibs was 14.4% (95% CI: 6.7 – 24.4%). There was no statistically significant difference between patients that assumed Coxibs and those that assumed placebo (total fixed effect relative risk = 0.86, 95% CI: 0.39 – 1.88, P = 0.7). Limitations: A proportion of patients received maintenance therapy with azathioprine or 6-mercaptopurine and these co-interventions could have protected against a Coxib-induced flare; furthermore, the duration of Coxib assumption in the prospective studies is shorter compared to that of the medical practice. Three of the studies included in our meta-analysis had an insufficient quality but due to the higher number of recruited patients, the studies with a better quality had a higher weight in the final result. Moreover, to assess the relative risk of flare up of IBD only randomized controlled trials have been used in the second meta-analysis. Conclusions: This meta-analysis showed that Coxibs are safe in most patients with IBD. Controlled trials of Coxibs compared with NSAIDs would be useful, at least in patients suffering from rheumatic pain refractory to standard treatment. Key words: Acute pain, ankylosing spondylitis, arthritis, coxibs, chronic pain, inflammatory bowel disease, rheumatic manifestations, sacroiliitis