Celecoxib for osteoarthritis

Primary tabs

SCIENCE
Celecoxib for osteoarthritis
Key Take-Away: 

The presented meta-analysis determined the efficacy and safety of celecoxib in treating osteoarthritis generating mixed results. Future evidence and prospectives are required.

Osteoarthritis (OA) is often associated with major disability and impaired quality of life.

ABSTRACT: 
Background: 

Osteoarthritis (OA) is often associated with major disability and impaired quality of life. There is currently no consensus on the best treatment to improve OA symptoms.

Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID). The main objective of the study was to assess the clinical benefits (pain, function, quality of life) and safety (withdrawals due to adverse effects, serious adverse effects, overall discontinuation rates) of celecoxib in OA.

Methods: 

Literature was searched in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials register up to April 11, 2017.

Pharmaceutical companies and authors of published articles were contacted. Published studies (full reports in a peer-reviewed journal) of prospective randomized controlled trials (RCTs) that compared oral celecoxib versus no intervention, placebo or another traditional NSAID in participants with clinically- or radiologically-confirmed primary OA of the knee or hip, or both knee and hip were included in the study. Two authors independently performed data extraction, quality assessment, and compared results. Main analyses for patient-reported outcomes of pain and physical function were conducted on studies with low risk of bias for sequence generation, allocation concealment and blinding of participants and personnel. 

Results: 

A total of 36 trials that provided data for 17,206 adults. Overall, 9402 participants received celecoxib 200 mg/day, and 7804 were assigned to receive either tNSAIDs (N = 1869) or placebo (N = 5935). Celecoxib was compared with placebo (32 trials), naproxen (6 trials) and diclofenac (3 trials). Studies were published between 1999 and 2014. Studies included participants with knee, hip or both OA; mean OA duration was 7.9 years. Most studies included predominantly white participants whose mean age was 62 (± 10) years; most participants were women. There were no concerns about the risk of bias for performance and detection bias, but selection bias was poorly reported in most trials. Most trials had high attrition bias, and there was evidence of selective reporting in a third of the studies.

Compared with placebo celecoxib slightly reduced pain on a 500-point Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale, accounting for 3% absolute improvement (95% CI 2% to 5% improvement) or 12% relative improvement (95% CI 7% to 18% improvement) (4 studies, 1622 participants). This improvement may not be clinically significant (high-quality evidence). Compared with placebo celecoxib slightly improved physical function on a 1700-point WOMAC scale, accounting for 4% absolute improvement (95% CI 2% to 6% improvement), 12% relative improvement (95% CI 5% to 19% improvement) (4 studies, 1622 participants). This improvement may not be clinically significant (high-quality evidence). There was no evidence of an important difference for withdrawals due to adverse events (Peto OR 0.99, 95% CI 0.85 to 1.15) (moderate-quality evidence due to study limitations). Results were inconclusive for numbers of participants experiencing any serious AEs (SAEs) (Peto OR 0.95, 95% CI 0.66 to 1.36), gastro-intestinal events (Peto OR 1.91, 95% CI 0.24 to 14.90) and cardiovascular events (Peto OR 3.40, 95% CI 0.73 to 15.88) (very low quality evidence due to serious imprecision and study limitations). However, regulatory agencies have warned of increased cardiovascular events for celecoxib.

There were inconclusive results regarding the effect on pain between celecoxib and tNSAIDs on a 100-point visual analogue scale (VAS), showing 5% absolute improvement (95% CI, 11% improvement to 2% worse), 11% relative improvement (95% CI, 26% improvement to 4% worse). Compared to a tNSAID celecoxib slightly improved physical function on a 100-point WOMAC scale, showing 6% absolute improvement (95% CI 6% to 11% improvement) and 16% relative improvement (95% CI 2% to 30% improvement). This improvement may not be clinically significant (low-quality evidence due to missing data and few participants) (1 study, 264 participants). Based on low or very low quality evidence (downgraded due to missing data, high risk of bias, few events and wide confidence intervals) results were inconclusive for withdrawals due to AEs (Peto OR 0.97, 95% CI 0.74 to 1.27), number of participants experiencing SAEs (Peto OR 0.92, 95% CI 0.66 to 1.28), gastro-intestinal events (Peto OR 0.61, 0.15 to 2.43) and cardiovascular events (Peto OR 0.47, 95% CI 0.17 to 1.25). In comparisons of celecoxib and placebo, there were no differences in pooled analyses between our main analysis with low risk of bias and all eligible studies. In comparisons of celecoxib and tNSAIDs, only one outcome showed a difference between studies at low risk of bias and all eligible studies: physical function (6% absolute improvement in the low risk of bias, no difference in all eligible studies). No studies included in the main comparisons measured the quality of life. Of 36 studies, 34 reported funding by drug manufacturers, and in 34 studies one or more study authors were employees of the sponsor. 

Conclusion: 

The study was unable to obtain data from three studies, which included 15,539 participants, and classified as awaiting assessment. Current evidence indicates that celecoxib is slightly better than placebo and some tNSAIDs in reducing pain and improving physical function.

Results are uncertain if harms differ among celecoxib and placebo or tNSAIDs due to a risk of bias, low-quality evidence for many outcomes, and that some study authors and Pfizer declined to provide data from completed studies with large numbers of participants. To fill the evidence gap, it is required to access existing data and new, independent clinical trials to investigate benefits and harms of celecoxib versus tNSAIDs for people with osteoarthritis, with longer follow-up and more direct head-to-head comparisons with other tNSAIDs. 

Source:

Cochrane Database Syst Rev. 2017 May 22;5: CD009865

Link to the source:

https://www.ncbi.nlm.nih.gov/pubmed/28530031

The original title of the article:

Celecoxib for osteoarthritis

Authors:

Puljak L et al.

Log in or register to post comments