Current Evidence on Celecoxib Safety in the Management of Chronic Musculoskeletal Conditions: An Umbrella Review

Our objective was to systematically synthesize and evaluate the existing evidence from meta-syntheses (systematic reviews and meta-analyses) reporting on the safety of celecoxib in adults with chronic musculoskeletal disorders. We conducted a comprehensive literature search in November 2024 across MEDLINE, Cochrane Central, and Scopus databases, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines for umbrella reviews. Only systematic reviews and meta-analyses involving celecoxib safety in osteoarthritis, rheumatoid arthritis, or ankylosing spondylitis were included. We assessed the risk of bias using the AMSTAR-2 tool and graded the certainty of evidence using GRADE. Of 2294 retrieved records, 16 systematic reviews based on randomized controlled trials met the inclusion criteria (14 of 16 were rated as critically low quality). Celecoxib was consistently associated with a lower risk of gastroduodenal ulcers than were non-selective non-steroidal anti-inflammatory drugs (NSAIDs), and some studies also reported fewer gastrointestinal complaints and serious events with celecoxib than with non-selective NSAIDs. Cardiovascular safety outcomes were generally similar to those with non-selective NSAIDs, although one meta-analysis showed a lower risk of cardiovascular mortality with celecoxib. Compared with placebo or non-selective NSAIDs, celecoxib did not increase the risk of renal dysfunction or elevated creatinine and may be associated with fewer renal adverse events. Evidence on all-cause mortality was limited and inconsistent, but one study suggested a lower risk than with non-selective NSAIDs. Celecoxib appears to offer better gastrointestinal safety than non-selective NSAIDs. Although data on cardiovascular, renal, and mortality outcomes suggest possible advantages, the evidence remains limited and of low certainty. Moreover, some real-world evidence raises concerns in specific high-risk populations. Future research should integrate data from both randomized trials and observational studies to better inform long-term safety assessments and guide individualized treatment decisions.