EXTENDED REPORT

Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis

T Pincus¹, G Koch², H Lei³, B Mangal³, T Sokka^1,4, R Moskowitz⁵, F Wolfe⁶, A Gibofsky⁷, L Simon⁸, S Zlotnick³, J G Fort³

¹ Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
² Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
³ Pfizer Corporation, USA
⁴ Department of Medicine, Jyvaskyla Central Hospital, Jyvaskyla, Finland
⁵ Division of Rheumatology, Case-Western University, Cleveland, OH 44106, USA
⁶ Wichita Arthritis Center, University of Kansas School of Medicine, 1035 North Emporia, Suite 230, Wichita, KS 67214, USA
⁷ Hospital for Special Surgery – Weill Medical College of Cornell University, New York, NY, USA
⁸ Department of Medicine, Harvard University, Boston, MA 02115, USA

Correspondence to:
Professor T Pincus
Division of Rheumatology and Immunology, Vanderbilt University School of Medicine, 203 Oxford House, Box 5, Nashville, TN 37232–4500, USA; t.pincus{at}vanderbilt.edu

Background: Acetaminophen (paracetamol) is recommended as the initial pharmacological treatment for knee or hip osteoarthritis. However, survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 specific inhibitors.

Design: Two randomised, double blind, placebo controlled, crossover multicentre clinical trials, Patient Preference for Placebo, Acetaminophen or Celecoxib Efficacy Studies (PACES).

Patients: Osteoarthritis of knee or hip.

Intervention: "Wash out" of treatment; randomisation; 6 weeks of celecoxib 200 mg/day, acetaminophen 1000 mg four times a day, or placebo; second "wash out;" crossover to 6 weeks of second treatment.

Measurements: Western Ontario McMaster Osteoarthritis Index (WOMAC), visual analogue pain scale, patient preference between two treatments.

Results: Celecoxib was more efficacious than acetaminophen in both periods in both studies; WOMAC and pain scale scores differed at p<0.05 in period II and both periods combined of PACES-a and in periods I and II and both periods combined in PACES-b, but not in period I of PACES-a. Acetaminophen was more efficacious than placebo, generally p<0.05 in PACES-b, and >0.05 in PACES-a. Patient preferences were 53% celecoxib v 24% acetaminophen in PACES-a (p<0.001) and 50% v 32% in PACES-b (p = 0.009); 37% acetaminophen v 28% placebo in PACES-a (p = 0.340) and 48% v 24% in PACES-b (p = 0.007). No clinically or statistically significant differences were seen in adverse events or tolerability among the three treatment groups.

Conclusions: Greater efficacy was seen for celecoxib v acetaminophen v placebo, while adverse events and tolerability were similar. Variation in results and statistical significance in the two different trials are of interest.

Abbreviations: MDHAQ, Multidimensional Health Assessment Questionnaire; NSAIDs, non-steroidal anti-inflammatory drugs; SF-36, Short Form-36; WOMAC, Western Ontario McMaster Osteoarthritis Index

Keywords: celecoxib; osteoarthritis; acetaminophen; placebo; WOMAC; pain visual analogue scale; paracetamol

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