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Meta-Analysis
. 2017 May 22;5(5):CD009865.
doi: 10.1002/14651858.CD009865.pub2.

Celecoxib for osteoarthritis

Livia Puljak  1 , Ana Marin  2 , Davorka Vrdoljak  3 , Filipa Markotic  4 , Ana Utrobicic  5 , Peter Tugwell  6
Affiliations
Meta-Analysis

Celecoxib for osteoarthritis

Livia Puljak et al. Cochrane Database Syst Rev. .

Abstract

Background: Osteoarthritis (OA) is the most common form of arthritis and is caused by degeneration of the joint cartilage and growth of new bone, cartilage and connective tissue. It 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).

Objectives: 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 osteoarthritis (OA).

Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials registers up to April 11, 2017, as well as reference and citation lists of included studies. Pharmaceutical companies and authors of published articles were contacted.

Selection criteria: We included 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 (tNSAID) in participants with clinically- or radiologically-confirmed primary OA of the knee or hip, or both knee and hip.

Data collection and analysis: 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.

Main results: We included 36 trials that provided data for 17,206 adults: 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 knee and hip 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 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. Celecoxib versus placeboCompared 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. Celecoxib versus tNSAIDsThere 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) (2 studies, 1180 participants, moderate quality evidence due to publication bias).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 low risk of bias, no difference in all eligible studies).No studies included in the main comparisons measured 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.

Authors' conclusions: We are highly reserved about results due to pharmaceutical industry involvement and limited data. We were 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. We are uncertain if harms differ among celecoxib and placebo or tNSAIDs due to 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, we need 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.

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Conflict of interest statement

Livia Puljak: None known. Ana Marin: None known. Davorka Vrdoljak: None known. Filipa Markotic: None known. Ana Utrobicic: None known. Peter Tugwell: None known.

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
4
4
Funnel plot of comparison: 1 Celecoxib versus placebo, outcome: 1.3 Number withdrawn due to adverse events.
5
5
Funnel plot of comparison: 1 Celecoxib versus placebo, outcome: 1.4 Number experiencing any serious adverse events.
1.1
1.1. Analysis
Comparison 1 Celecoxib versus placebo, Outcome 1 Pain.
1.2
1.2. Analysis
Comparison 1 Celecoxib versus placebo, Outcome 2 Physical function.
1.3
1.3. Analysis
Comparison 1 Celecoxib versus placebo, Outcome 3 Number withdrawn due to adverse events.
1.4
1.4. Analysis
Comparison 1 Celecoxib versus placebo, Outcome 4 Number experiencing any serious adverse events.
1.5
1.5. Analysis
Comparison 1 Celecoxib versus placebo, Outcome 5 Number experiencing gastro‐intestinal events (perforation, ulcer, bleeds).
1.6
1.6. Analysis
Comparison 1 Celecoxib versus placebo, Outcome 6 Number experiencing cardiovascular events (myocardial infarction, stroke).
2.1
2.1. Analysis
Comparison 2 Celecoxib versus tNSAIDs, Outcome 1 Pain.
2.2
2.2. Analysis
Comparison 2 Celecoxib versus tNSAIDs, Outcome 2 Physical function.
2.3
2.3. Analysis
Comparison 2 Celecoxib versus tNSAIDs, Outcome 3 Number withdrawn due to adverse events.
2.4
2.4. Analysis
Comparison 2 Celecoxib versus tNSAIDs, Outcome 4 Number experiencing any serious adverse events.
2.5
2.5. Analysis
Comparison 2 Celecoxib versus tNSAIDs, Outcome 5 Number experiencing gastro‐intestinal events (perforation, ulcer, bleeds).
2.6
2.6. Analysis
Comparison 2 Celecoxib versus tNSAIDs, Outcome 6 Number experiencing cardiovascular events (myocardial infarction, stroke).
3.1
3.1. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 1 All pain < 24 weeks.
3.2
3.2. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 2 Pain VAS at 6 weeks.
3.3
3.3. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 3 Pain VAS at 12 weeks.
3.4
3.4. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 4 Pain VAS at 13 weeks.
3.5
3.5. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 5 Pain on walking VAS at 6 weeks.
3.6
3.6. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 6 Pain on walking WOMAC at 12 weeks.
3.7
3.7. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 7 Pain WOMAC at 6 weeks.
3.8
3.8. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 8 Pain WOMAC at 12 weeks.
3.9
3.9. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 9 Pain WOMAC at 13 weeks.
3.10
3.10. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 10 Pain WOMAC at 24 weeks.
3.11
3.11. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 11 All physical function < 24 weeks.
3.12
3.12. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 12 Physical function WOMAC at 6 weeks.
3.13
3.13. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 13 Physical function WOMAC at 12 weeks.
3.14
3.14. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 14 Physical function WOMAC at 13 weeks.
3.15
3.15. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 15 Physical function WOMAC at 24 weeks.
3.16
3.16. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 16 Quality of life: SF‐36 physical component scores.
3.17
3.17. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 17 Quality of life: SF‐36 mental component scores.
3.18
3.18. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 18 Number of responders with at least 50% improvement in WOMAC pain.
3.19
3.19. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 19 Number withdrawn due to adverse events.
3.20
3.20. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 20 Number experiencing any serious adverse events.
3.21
3.21. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 21 Number experiencing gastro‐intestinal events (perforation, ulcer, bleeds).
3.22
3.22. Analysis
Comparison 3 Celecoxib versus placebo (all eligible studies), Outcome 22 Number experiencing cardiovascular events (myocardial infarction, stroke).
4.1
4.1. Analysis
Comparison 4 Celecoxib versus tNSAIDs (all eligible studies), Outcome 1 All pain under 24 weeks.
4.2
4.2. Analysis
Comparison 4 Celecoxib versus tNSAIDs (all eligible studies), Outcome 2 All pain over 24 weeks.
4.3
4.3. Analysis
Comparison 4 Celecoxib versus tNSAIDs (all eligible studies), Outcome 3 All physical function under 24 weeks.
4.4
4.4. Analysis
Comparison 4 Celecoxib versus tNSAIDs (all eligible studies), Outcome 4 Number withdrawn due to adverse events.
4.5
4.5. Analysis
Comparison 4 Celecoxib versus tNSAIDs (all eligible studies), Outcome 5 Number experiencing any serious adverse events.
4.6
4.6. Analysis
Comparison 4 Celecoxib versus tNSAIDs (all eligible studies), Outcome 6 Number experiencing gastro‐intestinal events (perforation, ulcer, bleeds).
4.7
4.7. Analysis
Comparison 4 Celecoxib versus tNSAIDs (all eligible studies), Outcome 7 Number experiencing cardiovascular events (myocardial infarction, stroke).
5.1
5.1. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 1 All pain ≤ 24 weeks.
5.2
5.2. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 2 Pain VAS at 6 weeks.
5.3
5.3. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 3 Pain VAS at 12 weeks.
5.4
5.4. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 4 Pain WOMAC at 6 weeks.
5.5
5.5. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 5 Pain WOMAC at 12 weeks.
5.6
5.6. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 6 Pain WOMAC at 6 months.
5.7
5.7. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 7 All physical function ≤ 24 weeks.
5.8
5.8. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 8 Physical function WOMAC at 6 weeks.
5.9
5.9. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 9 Physical function WOMAC at 12 weeks.
5.10
5.10. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 10 Physical function WOMAC at 6 months.
5.11
5.11. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 11 Number withdrawn due to adverse events.
5.12
5.12. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 12 Number experiencing any serious adverse events.
5.13
5.13. Analysis
Comparison 5 Celecoxib versus naproxen 1000 mg, Outcome 13 Number experiencing gastro‐intestinal events (perforation, ulcer, bleeds).
6.1
6.1. Analysis
Comparison 6 Celecoxib versus diclofenac 100 mg, Outcome 1 Pain VAS at 1 year.
6.2
6.2. Analysis
Comparison 6 Celecoxib versus diclofenac 100 mg, Outcome 2 Number withdrawn due to adverse events.
6.3
6.3. Analysis
Comparison 6 Celecoxib versus diclofenac 100 mg, Outcome 3 Number experiencing any serious adverse events.
6.4
6.4. Analysis
Comparison 6 Celecoxib versus diclofenac 100 mg, Outcome 4 Number experiencing gastro‐intestinal events (perforation, ulcer, bleeds).
6.5
6.5. Analysis
Comparison 6 Celecoxib versus diclofenac 100 mg, Outcome 5 Number experiencing cardiovascular events (myocardial infarction, stroke).
7.1
7.1. Analysis
Comparison 7 Celecoxib versus diclofenac 150 mg, Outcome 1 Pain VAS at 6 weeks.
7.2
7.2. Analysis
Comparison 7 Celecoxib versus diclofenac 150 mg, Outcome 2 Pain WOMAC at 6 weeks.
7.3
7.3. Analysis
Comparison 7 Celecoxib versus diclofenac 150 mg, Outcome 3 Pain on walking at 12 weeks.
7.4
7.4. Analysis
Comparison 7 Celecoxib versus diclofenac 150 mg, Outcome 4 Physical function WOMAC at 6 weeks.
7.5
7.5. Analysis
Comparison 7 Celecoxib versus diclofenac 150 mg, Outcome 5 Number withdrawn due to adverse events.
7.6
7.6. Analysis
Comparison 7 Celecoxib versus diclofenac 150 mg, Outcome 6 Number experiencing any serious adverse events.
7.7
7.7. Analysis
Comparison 7 Celecoxib versus diclofenac 150 mg, Outcome 7 Number experiencing gastro‐intestinal events (perforation, ulcer, bleeds).
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Update of

References

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    1. Tannenbaum H, Berenbaum F, Reginster JY, Zacher J, Robinson J, Poor G, et al. Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a 13 week, randomised, double blind study versus placebo and celecoxib. Annals of the Rheumatic Diseases 2004;63(11):1419‐26. - PMC - PubMed
Williams 2000 {published data only}
    1. Williams GW, Ettlinger RE, Ruderman EM, Hubbard RC, Lonien ME, Yu SS, et al. Treatment of osteoarthritis with a once‐daily dosing regimen of celecoxib: a randomized, controlled trial. Journal of Clinical Rheumatology 2000;6(2):65‐74. - PubMed
Williams 2001 {published data only}
    1. Williams GW, Hubbard RC, Yu SS, Zhao W, Geis GS. Comparison of once‐daily and twice‐daily administration of celecoxib for the treatment of osteoarthritis of the knee. Clinical Therapeutics 2001;23(2):213‐27. - PubMed

References to studies excluded from this review

Adegbehingbe 2008 {published data only}
    1. Adegbehingbe OO, Adesanya SA, Idowu TO, Okimi OC, Oyelami OA, Iwalewa EO. Clinical effects of Garcinia kola in knee osteoarthritis. Journal of Orthopaedic Surgery and Research 2008;3(34):1‐10. - PMC - PubMed
Andrews 1999 {published data only}
    1. Andrews SA, Wallace CK, Davis RL. Celecoxib: a COX‐2 inhibitor. American Journal of Managed Care 1999;5(4):511‐8. - PubMed
Angiolillo 2014 {published data only}
    1. Angiolillo DJ, Datto C, Raines S, Yeomans ND. Impact of concomitant low‐dose aspirin on the safety and tolerability of naproxen and esomeprazole magnesium delayed‐release tablets in patients requiring chronic nonsteroidal anti‐inflammatory drug therapy: an analysis from 5 Phase III studies. Journal of Thrombosis and Thrombolysis 2014;38(1):11‐23. - PubMed
Ashcroft 2001 {published and unpublished data}
    1. Ashcroft DM, Chapman SR, Clark WK, Millson DS. Upper gastroduodenal ulceration in arthritis patients treated with celecoxib. Annals of Pharmacotherapy 2001;35(7‐8):829‐34. - PubMed
Battisti 2004 {published data only}
    1. Battisti WP, Katz NP, Weaver AL, Matsumoto AK, Kivitz AJ, Polis AB, et al. Pain management in osteoarthritis: A focus on onset of efficacy—a comparison of rofecoxib, celecoxib, acetaminophen, and nabumetone across four clinical trials. Journal of Pain 2004;5(9):511‐20. - PubMed
Bensen 2000 {published data only}
    1. Bensen WG. Antiinflammatory and analgesic efficacy of COX‐2 specific inhibition: from investigational trials to clinical experience. Journal of Rheumatology 2000;60(Supp):17‐24. - PubMed
Bensen 2000b {published data only}
    1. Bensen WG, Zhao SZ, Burke TA, Zabinski RA, Makuch RW, Maurath CJ, et al. Upper gastrointestinal tolerability of celecoxib, a COX‐2 specific inhibitor, compared to naproxen and placebo. Journal of Rheumatology 2000;27(8):1876‐83. - PubMed
Bianchi 2003 {published data only}
    1. Bianchi M, Broggini M. A randomised, double‐blind, clinical trial comparing the efficacy of nimesulide, celecoxib and rofecoxib in osteoarthritis of the knee. Drugs 2003;63(Suppl 1):37‐46. - PubMed
Bianchi 2007 {published data only}
    1. Bianchi M, Broggini M, Balzarini P, Franchi S, Sacerdote P. Effects of nimesulide on pain and on synovial fluid concentrations of substance P, interleukin‐6 and interleukin‐8 in patients with knee osteoarthritis: comparison with celecoxib. International Journal of Clinical Practice 2007;61(8):1270‐7. - PubMed
Bingham 2008 {published data only}
    1. Bingham CO 3rd, Bird SR, Smugar SS, Xu X, Tershakovec AM. Responder analysis and correlation of outcome measures: pooled results from two identical studies comparing etoricoxib, celecoxib, and placebo in osteoarthritis. Osteoarthritis and Cartilage 2008;16(11):1289‐93. - PubMed
Bingham 2009 {published data only}
    1. Bingham CO 3rd, Smugar SS, Wang H, Tershakovec AM. Early response to COX‐2 inhibitors as a predictor of overall responsein osteoarthritis: pooled results from two identical trials comparing etoricoxib, celecoxib and placebo. Rheumatology 2009;48(9):1122–7. - PubMed
Bingham 2011 {published data only}
    1. Bingham CO 3rd, Smugar SS, Wang H, Peloso PM, Gammaitoni A. Predictors of response to cyclo‐oxygenase‐2 inhibitors in osteoarthritis: pooled results from two identical trials comparing etoricoxib, celecoxib, and placebo. Pain Medicine 2011;12(3):352–61. - PubMed
Brereton 2014 {published data only}
    1. Brereton N, Pennington B, Ekelund M, Akehurst R. A cost‐effectiveness analysis of celecoxib compared with diclofenac in the treatment of pain in osteoarthritis (OA) within the Swedish health system using an adaptation of the NICE OA model. Journal of Medical Economics 2014;17(9):677‐84. - PubMed
Castgillo 2015 {published data only}
    1. Castgillo JR, Hochberg HC, Martel‐Pelletier J, Monfort J, Moller I, Arden N, et al. Combined chondroitin sulfate and glucosamine versus celecoxib for painful knee osteoarthritis: Post‐hoc analyses by Kellgren and Lawrence grade and C‐reactive protein level from a randomized, double‐blind, multicentre clinical trial. Clinical Therapeutics 2015;37(8):e122. [DOI: 10.1016/j.clinthera.2015.05.349] - DOI
Castillo 2014 {published data only}
    1. Castillo JR, Hochberg MC, Martel‐Pelletier J, Monfort J, Mooller I, Arden N, et al. Multicentric osteoarthritis intervention study with sysadoa (moves): Effects of combined glucosamine hydrochloride and chondroitin sulfate vs. celecoxib for painful knee osteoarthritis. Basic and Clinical Pharmacology and Toxicology 2014;115:12.
Chan 2015 {published data only}
    1. Chan FKL, Ching J, Cheung C, Lam LYK, Au KWL, Ng SC, et al. Prevention of recurrent ulcer bleeding in arthritis patients with high cardiovascular and high gastrointestinal risks: A 18‐month, double‐blind, randomized trial. Gastroenterology 2015;148(4 Suppl 1):S157‐8.
Detrembleur 2005 {published data only}
    1. Detrembleur C, Nayer J, Hecke A. Celecoxib improves the efficiency of the locomotor mechanism in patients with knee osteoarthritis. A randomised, placebo, double‐blind and cross‐over trial. Osteoarthritis and Cartilage 2005;13(3):206‐10. - PubMed
Dougados 2007 {published data only}
    1. Dougados M, Moore A, Yu S, Gitton X. Evaluation of the patient acceptable symptom state in a pooled analysis of two multicentre, randomised, double‐blind, placebo‐controlled studies evaluating lumiracoxib and celecoxib in patients with osteoarthritis. Arthritis Research and Therapy 2007;9(1):R11. - PMC - PubMed
Essex 2014b {published data only}
    1. Essex MN, Brown PB, Sands GH. The efficacy of continuous versus intermittent celecoxib treatment in osteoarthritis patients aged < 60 and > 60 years. International Journal of Clinical Rheumatology 2014;9(1):13‐20. - PMC - PubMed
Gallelli 2013 {published data only}
    1. Gallelli L, Galasso O, Falcone D, Southworth S, Greco M, Ventura V, et al. The effects of nonsteroidal anti‐inflammatory drugs on clinical outcomes, synovial fluid cytokine concentration and signal transduction pathways in knee osteoarthritis. A randomized open label trial. Osteoarthritis and Cartilage 2013;21(9):1400‐8. - PubMed
Hawel 2003 {published data only}
    1. Hawel R, Klein G, Singer F, Mayrhofer F, Kahler ST. Dexibuprofen in a special crystal form versus celecoxib in the management of osteoarthritis of the hip. Wiener Medizinische Wochenschrift 2002;152(Suppl 112):13.
    1. Hawel R, Klein G, Singer F, Mayrhofer F, Kähler ST. Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip. International Journal of Clinical Pharmacology and Therapeutics 2003;41(4):153‐64. - PubMed
Henrotin 2015 {published data only}
    1. Henrotin Y, Arden N, Berenbaum F, Blanco FJ, Castillo JR, Conaghan PG, et al. Combined chondroitin sulfate and glucosamine is more efficient than celebrex in reducing serum levels of Coll2‐1, a cartilage degradation biomarker, in patients with severe OA: Results from a randomized, doubleblind, multicentric clinical trial. Osteoarthritis and Cartilage 2015;23(Suppl 2):A86.
Hirayama 2014 {published data only}
    1. Hirayama A, Tanahashi N, Daida H, Ishiguro N, Chcachin M, Sugioka T, et al. Accept study investigators in Japan. Assessing the cardiovascular risk between celecoxib and nonselective nonsteroidal antiinflammatory drugs in patients with rheumatoid arthritis and osteoarthritis. Circulation Journal 2014;78(1):194‐205. - PubMed
Hochberg 2014a {published data only}
    1. Hochberg M, Martel‐Pelletier J, Monfort J, Moller I, Castillo JR, Arden N, et al. Multicentric osteoarthritis intervention study with sysadoa (MOVES): Effects of combined glucosamine hydrochloride and chondroitin sulfate vs celecoxib for painful knee osteoarthritis. Annals of the Rheumatic Diseases. 2014; Vol. 73, issue 11.
Hochberg 2014b {published data only}
    1. Hochberg MC, Martel‐Pelletier J, Monfort J, Moller I, Du Souich P, Pelletier JP. Randomized, double‐blind, multicenter, non inferiority clinical trial with combined glucosamine and chondroitin sulfate vs celecoxib for painful knee osteoarthritis. Osteoarthritis and cartilage. 2014; Vol. 22, issue 24.
Johnson 2003 {published data only}
    1. Johnson M, Seaton T. Comparing celecoxib with traditional nonsteroidal anti‐inflammatory drugs. Journal of Family Practice 2003;52(2):96‐8. - PubMed
Leeb 2004 {published data only}
    1. Leeb BF, Bucsi L, Keszthelyi B, Böhmova J, Valesova M, Hawel R, et al. Treatment of osteoarthritis of the knee joint. Efficacy and tolerance to acemetacin slow release in comparison to celecoxib [Behandlung der Gonarthrose. Wirksamkeit und Verträglichkeit von retardiertem Acemetacin im Vergleich zu Celecoxib]. Der Orthopäde 2004;33(9):1032‐41. - PubMed
Luyten 2007 {published data only}
    1. Luyten FP, Geusens P, Malaise M, Clerck L, Westhovens R, Raeman F, et al. A prospective randomised multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip. Annals of the Rheumatic Diseases 2007;66(1):99‐106. - PMC - PubMed
Moore 2009 {published data only}
    1. Moore RA, Peloso PM, Mehta A, Gammaitoni A. Baseline predictors of improvement in pain using a pooled analysis of 7 randomized controlled studies in patients with osteoarthritis (OA). European Journal of Pain 2009;13(S1):S82.
NCT02192190 {published data only}
    1. Jin Y, Smith C, Monteith D, Brown R, Camporeale A, McNearney T, Deeg M, Raddad E, Pena A, Kivitz A, Schnitzer T. LY2951742, a monoclonal antibody against CGRP, failed to reduce signs and symptoms of knee osteoarthritis. Osteoarthritis and Cartilage 2016;24(S1):S50. - PubMed
    1. NCT02192190. A study of LY2951742 in participants with mild to moderate osteoarthritis knee pain. clinicaltrials.gov/show/NCT02192190 (first received 14 July 2014).
    1. Smith C, Jin Y, Raddad E, McNearney T, Ni X, Monteith D, Brown R, Deeg M, Schnitzer T. Applications of Bayesian statistical methodology to success criteria: A case study of a phase 2 design with interim futility assessment in patients with knee osteoarthritis. Osteoarthritis and Cartilage 2016;24(S1):S185.
Nissen 2016 {published data only}
    1. Nissen SE, Yeomans ND, Solomon DH, Lüscher TF, Libby P, Husni ME, Graham DY, Borer JS, Wisniewski LM, Wolski KE, Wang Q, Menon V, Ruschitzka F, Gaffney M, Beckerman B, Berger MF, Bao W, Lincoff AM, PRECISION Trial Investigators. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. N Engl J Med 2016;375(26):2519‐29. - PubMed
Ogunlade 2005 {published data only}
    1. Ogunlade SO, Oginni LM, Nwadiaro HC, Popoola O, Enweani UN, Onabowale BO, et al. The efficacy and toleration of celecoxib (Celebrex) in the treatment of osteoarthritis in Nigeria: a multicentre study. West African Journal of Medicine 2005;24(3):263‐7. - PubMed
Ozgocmen 2005 {published data only}
    1. Ozgocmen S, Ardicoglu O, Erdogan H, Fadillioglu E, Gudul H. In vivo effect of celecoxib and tenoxicam on oxidant/ anti‐oxidant status of patients with knee osteoarthritis. Annals of Clinical and Laboratory Science 2005;35(2):137‐43. - PubMed
Pelletier 2016 {published data only}
    1. Pelletier JP, Raynauld JP, Beaulieu A, Bessette L, Morin F, Fernandes AJ, et al. In a two‐year double‐blind randomized controlled multicenter study, chondroitin sulfate was significantly superior to celecoxib at reducing cartilage loss with similar efficacy at reducing disease symptoms in knee osteoarthritis patients. Osteoarthritis and Cartilage 2016;24(Suppl. 1):S189–S190.
Rozenberg 2008 {published data only}
    1. Rozenberg S, Méric G, Jeanpetit Y. Changes in quality of life in patients with osteoarthritis treated with celecoxib: the Qualice study. Presse Médicale 2008;37(4 Pt 1):571‐8. - PubMed
Sakamoto 2011 {published data only}
    1. Sakamoto C, Soen S. Efficacy and safety of the selective cyclooxygenase‐2 inhibitor celecoxib in the treatment of rheumatoid arthritisand osteoarthritis in Japan. Digestion 2011;83(1‐2):108‐23. - PubMed
Sampalis 2012 {published data only}
    1. Sampalis JS, Brownell LA. A randomized, double blind, placebo and active comparator controlled pilot study of UP446, a novel dual pathway inhibitor anti‐inflammatory agent of botanical origin. Nutrition Journal 2012;11:21. - PMC - PubMed
Sands 2013 {published data only}
    1. Sands GH, Brown PB, Essex MN. The efficacy of continuous versus Intermittent celecoxib treatment in osteoarthritis patients with body mass index ≥30 and <30 kg/m². Open Rheumatology Journal 2013;7:32‐7. - PMC - PubMed
Schnitzer 2015 {published data only}
    1. Schnitzer TJ, Ekman EF, Spierings ELH, Greenberg HS, Smith MD, Brown MT, et al. Efficacy and safety of tanezumab monotherapy or combined with non‐steroidal anti‐inflammatory drugs in the treatment of knee or hip osteoarthritis pain. Annals of the Rheumatic Diseases 2015;74(6):1202‐11. - PubMed
Silverstein 2000 {published data only}
    1. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti‐inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long‐term Arthritis Safety Study. JAMA 2000;284(10):1247‐55. - PubMed
Simon 1998 {published data only}
    1. Simon LS, Lanza FL, Lipsky PE, Hubbard RC, Talwalker S, Schwartz BD, et al. Preliminary study of the safety and efficacy of SC‐58635, a novel cyclooxygenase 2 inhibitor: efficacy and safety in two placebo‐controlled trials in osteoarthritis and rheumatoid arthritis, and studies of gastrointestinal and platelet effects. Arthritis and Rheumatism 1998;41(9):1591‐602. - PubMed
Stam 2012 {published data only}
    1. Stam W, Jansen J, Taylor S. Efficacy of etoricoxib, celecoxib, lumiracoxib, non‐selective NSAIDs, and acetaminophen in osteoarthritis: A mixed treatment comparison. Open Rheumatology Journal 2012;6:6‐20. - PMC - PubMed
Stengaard‐Pedersen 2004 {published data only}
    1. Stengaard‐Pedersen K, Ekesbo R, Karvonen AL, Lyster M. Celecoxib 200 mg q.d. is efficacious in the management of osteoarthritis of the knee or hip regardless of the time of dosing. Rheumatology 2004;43(5):592–5. - PubMed
Strand 2011 {published data only}
    1. Strand V, Simon LS, Dougados M, Sands GH, Bhadra P, Breazna A, et al. Treatment of osteoarthritis with continuous versus intermittent celecoxib. Journal of Rheumatology 2011;38(12):2625‐34. - PubMed
Taşcioğlu 2004 {published data only}
    1. Taşcıoğlu F, Öner C, Aydemir A. Comparison of the efficacy of celecoxib and diclofenac sodium in the treatment of knee osteoarthritis [Diz osteoartritinin tedavisinde selekoksib ve diklofenak sodyum etkinliğinin karşılaştırılması]. Türkiye Fiziksel Tıp ve Rehabilitasyon Derneği 2004;50(4):7‐12.
Tive 2015 {published data only}
    1. Tive L, Radin D, Bello A, Nguyen H, Brown MT, West CR, et al. Pooled efficacy and safety from phase 3 controlled studies of tanezumab in patients with osteoarthritis. Arthritis & Rheumatology 2015;67(Suppl 10).
Tran 2004 {published data only}
    1. Tran F, Boggie DT, Delattre ML, Schaefer MG, Morreale AP, Plowman BK. Therapeutic interchange involving replacement of rofecoxib or celecoxibwith valdecoxib. American Journal of Health‐System Pharmacy 2004;61(13):1391‐4. - PubMed
Trudeau 2015 {published data only}
    1. Trudeau J, Inwegen R, Eaton T, Bhat G, Paillard F, Ng D, et al. Assessment of pain and activity using an electronic pain diary and actigraphy device in a randomized, placebo‐controlled crossover trial of celecoxib in osteoarthritis of the knee. Pain Practice 2015;15(3):247‐55. - PubMed
Tsvetkova 2001 {published data only}
    1. Tsvetkova ES, Alekseeva LI, Balabanova RM, Chichasova NV, Shostak NA, Shmidt EI. Effectiveness and tolerance of celebrex in osteoarthrosis (data of a Russian study). Terapevticheskii Arkhiv 2001;73(5):61‐3. - PubMed
Wittenberg 2006 {published data only}
    1. Wittenberg RH, Schell E, Krehan G, Maeumbaed R, Runge H, Schluter P, et al. First‐dose analgesic effect of the cyclo‐oxygenase‐2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double‐blind, placebo‐controlled comparison with celecoxib [NCT00267215]. Arthritis Research and Therapy 2006;8(2):R35. - PMC - PubMed
Wolfe 2004 {published data only}
    1. Wolfe F, Michaud K, Burke TA, Zhao SZ. Longer use of COX‐2‐specific inhibitors compared to nonspecific nonsteroidal antiinflammatory drugs: alongitudinal study of 3639 patients in community practice. Journal of Rheumatology 2004;31(2):355‐8. - PubMed
Yoo 2014a {published data only}
    1. Yoo MC, Yoo WH, Kang SB, Park YW, Kim SS, Moon KH, et al. Etoricoxib in the treatment of Korean patients with osteoarthritis. International Journal of Rheumatic Diseases 2014;17(Suppl 1):128.
    1. Yoo MC, Yoo WH, Kang SB, Park YW, Kim SS, Moon KH, et al. Etoricoxib in the treatment of Korean patients with osteoarthritis in a double‐blind, randomized controlled trial. Current Medical Research and Opinion 2014;30(12):2399‐2408. - PubMed
Yoo 2014b {published data only}
    1. Yoo WH, Yoo HG, Park S‐H, Baek HL, Lee YJ, Shim SC, et al. Efficacy and safety of PG201 (Layla) and celecoxib in the treatment of symptomatic knee osteoarthritis: a double‐blinded, randomized, multi‐center, active drug comparative, parallel‐group, non‐inferiority, phase III study. Rheumatology International 2014;34(10):1369‐78. - PubMed

References to studies awaiting assessment

Essex 2016 {published data only}
    1. Essex MN, O'Connell MA, Behar R, Bao W. Efficacy and safety of nonsteroidal anti‐inflammatory drugs in Asian patients with knee osteoarthritis: summary of a randomized, placebo‐controlled study. Int J Rheum Dis 2016;19(3):262‐70. - PMC - PubMed
EUCTR2005‐002772‐14‐GB {unpublished data only}
    1. EUCTR2005‐002772‐14‐GB. A 13‐week, multicenter, randomized, double‐blind, doubledummy, placebo‐controlled, parallel group trial of lumiracoxib (COX189) 100 mg o.d. in patients with primary hip osteoarthritis using celecoxib (200 mg o.d.) as a positive control. http://apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2005‐002772‐14‐GB (first received 14 October 2005).
Gordo 2017 {published data only}
    1. Gordo AC, Walker C, Armada B, Zhou D. Efficacy of celecoxib versus ibuprofen for the treatment of patients with osteoarthritis of the knee: A randomized double‐blind, non‐inferiority trial. J Int Med Res 2017;45(1):59‐74. - PMC - PubMed
Iyengar 2013 {published data only}
    1. Iyengar RL, Gandhi S, Aneja A, Thorpe K, Razzouk L, Greenberg J, et al. NSAIDs are associated with lower depression scores in patients with osteoarthritis. American Journal of Medicine 2013;126(11):1017. - PubMed
Lisse 2001 {published data only}
    1. Lisse J, Espinoza L, Zhao SZ, Dedhiya SD, Osterhaus JT. Functional status and health‐related quality of life of elderly osteoarthritic patients treated with celecoxib. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 2001;56(3):M167‐75. - PubMed
Mastbergen 2010 {published data only}
    1. Mastbergen SC, Boer TN, Huisman AM, Polak AA, Bijlsma JWJ, Lafeber FPJG. 9th World Congress of the International Cartilage Repair Society; 2010, Nov 26‐29, Barcelona, Spain.. 2010; Vol. 1, issue 2(S1):46S.
Reginster 2016 {published data only}
    1. Reginster JY. Pharmaceutical Grade Chondroitin Sulfate Improves Knee Osteoarthritis Symptoms More Than Placebo and As Much As Celecoxib: Results of the Chondroitin Vs Celecoxib Vs Placebo Trial (CONCEPT). Arthritis & Rheumatology 2016;68(S10).
Singh 2006 {published data only}
    1. Singh G, Fort JG, Goldstein JL, Levy RA, Hanrahan PS, Bello AE, et al. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS‐I study. American Journal of Medicine 2006;119(3):255‐66. - PubMed

References to ongoing studies

EUCTR2011‐005398‐22‐ES {unpublished data only}
    1. EUCTR2011‐005398‐22‐ES. Clinical study comparing a new signle dose chewable tablet as treatment knee osteoarthritis with moderate to severe pain, compared to placebo and celecoxib. apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2011‐005398‐22‐ES (first received 11 January 2012).
NCT01765296 {published data only}
    1. NCT01765296. Phase III study of CG100649 in osteoarthritis patients. clinicaltrials.gov/show/NCT01765296 (first received 8 January 2013).
NCT01768520 {unpublished data only}
    1. NCT01768520. Evaluation of the efficacy and safety of entelon tab. 150 mg in patients with osteoarthritis of knee. clinicaltrials.gov/ct2/show/NCT01768520 (first received 14 January 2013).
NCT02079727 {published data only}
    1. NCT02079727. Condrosulf vs celebrex vs placebo in the treatment of knee OA. clinicaltrials.gov/show/NCT02079727 (first received 28 February 2014).

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