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

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.