Osteoarthritis is the most common musculoskeletal condition worldwide, affecting up to 20% of adults in various populations (Ryan, 2018; Trouvin and Perrot, 2018). One of the leading causes of disability, osteoarthritis is characterised by inflammation, pain and reduced function in the affected joints (National Institute for Health and Care Excellence, 2014). Recommendations for osteoarthritis management centre on the reduction of pain and improving function. Management options include pharmacological, non-pharmacological and surgical methods, with pharmacological treatments used as an adjunct to non-pharmacological methods (Finney et al, 2019). While there is no consensus on the best pharmacological intervention for osteoarthritis, celecoxib is often considered for treatment.
A Cochrane systematic review indicated that celecoxib offers fewer gastrointestinal side effects than traditional non-steroidal anti-inflammatory drugs (tNSAIDs), such as naproxen or diclofenac, while having a similar level of efficacy (Puljak et al, 2017).
Objectives
The objectives of this Cochrane review were to assess the benefits and harms of using celecoxib in osteoarthritis. The benefits and harms considered included pain function, quality of life, withdrawals due to adverse effects, serious adverse effects and overall medication discontinuation rates.
Methods
The authors of this review searched for full peer-reviewed published reports and prospective randomised controlled trials in any language. Studies with fewer than 50 participants were excluded, as were those of less than 4 weeks' duration. The interventions examined included oral celecoxib 200 mg daily, either as a single daily dose or as a 100-mg dose twice daily versus no intervention, placebo or tNSAIDs. Major outcomes for harms and benefits were grouped as shown in Table 1.
| Benefits | Harms |
|---|---|
| Decreased pain | Withdrawal from study due to adverse events |
| Improved function | Serious adverse events |
| Better quality of life | Clinical presentation with perforation, ulcer or bleed |
| Cardiovascular outcomes |
Electronic databases, CENTRAL, Medline and Embase via Ovid were searched for eligible studies, as well as regulatory agency websites. The reference lists of all identified studies were also searched for relevant studies, in addition to trial registries such as www.clinicaltrials.gov and the World Health Organization International Clinical Trials Registry Platform.
Findings
From 7627 identified records from database searches and 2338 identified records from other sources, 36 studies were identified for inclusion in this review. All included studies were double-blinded randomised parallel-group trials, including a total of 17 206 participants. Some 9402 participants were assigned to a treatment group, receiving 200 mg celecoxib daily, and 7804 participants were assigned to a comparator group, receiving either tNSAIDs (N=1869) or placebo (N=5935). Of the 36 studies, 34 received funding from pharmaceutical companies that produced study drugs, and one study did not provide information regarding the source of funding. The last study had independent funding. In 34 studies, one or more study authors were employees of a pharmaceutical company producing the study drug. All included studies were found to have an unclear risk of bias, or high risk of bias, across at least two or more domains.
The celecoxib versus placebo comparison demonstrated that celecoxib is superior to placebo for pain management and physical function; however, the benefits only ranged from 3% to 6%—the minimal clinically important difference is considered to be 15% (Puljak et al, 2017). Overall harms were inconclusive due to low-quality evidence, risk of bias and imprecision. The celecoxib versus tNSAIDs comparison demonstrated that there was no significant difference in harms or benefits; the authors were unable to assess overall harms due to the low or very low quality of evidence.
Conclusion
Celecoxib was found to be slightly better than placebo for pain and function, but this improvement is unlikely to be clinically significant. The risk of harm results were inconclusive due to the risk of bias and the potential for positive gearing of study results due to industry funding sources. The authors attempted to contact industry sources for further clarification on data and to retrieve additional data for consideration; however, these attempts were unsuccessful. This clarification and additional data are required to ensure an accurate picture of the evidence. Future studies are required to investigate the benefits and harms of celecoxib versus tNSAIDs for osteoarthritis. It is also recommended that future studies consider the benefits and harms of celecoxib in patients with comorbidities and those at higher risk of cardiovascular disease.
Implications for practice
This review has several implications for nursing practice. Ensuring that all patients receiving celecoxib or NSAIDs as part of their osteoarthritis management plan are regularly reviewed for pain management, function and any adverse effects is essential, as well as assessing their cardiovascular health. Patient education on non-pharmacological interventions, such as heat therapy, to assist with the self-management of osteoarthritis symptoms may be effective (York, 1995; Lizarondo, 2018). Referral to a suitable exercise programme is a core component of treatment, and some patients may find a referral to physiotherapy useful (Slade, 2018; 2019a; 2019b; Picot, 2019). In the event a patient with osteoarthritis is overweight, support or referral to assist with weight management is recommended (Paans et al, 2013).