Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee

N Engl J Med. 1991 Jul 11;325(2):87-91. doi: 10.1056/NEJM199107113250203.


Background: The optimal short-term, symptomatic therapy for osteoarthritis of the knee has not been fully determined. Accordingly, we compared the efficacy of a nonsteroidal antiinflammatory drug, ibuprofen, given in either an antiinflammatory dose (high dose) or an analgesic dose (low dose), with that of acetaminophen, a pure analgesic.

Methods: In a randomized, double-blind trial, 184 patients with chronic knee pain due to osteoarthritis were given either 2400 or 1200 mg of ibuprofen per day or 4000 mg of acetaminophen per day. They were evaluated after a washout period of three to seven days before the beginning of the study, and again after four weeks of treatment. The major measures of outcome included scores on the pain and disability scales of the Stanford Health Assessment Questionnaire (range of possible scores, 0 to 3), scores on the visual-analogue scales for pain at rest and pain while walking, the time needed to walk 50 ft (15 m), and the physician's global assessment of the patient's arthritis.

Results: Seventy-eight percent of the patients completed four weeks of therapy. No significant differences were noted among the three treatment groups with respect to failure to complete the trial because of noncompliance or adverse events. All three groups had improvement in all major outcome variables, and the groups did not differ significantly in the magnitude of improvement in most variables. The mean improvement (change) in the scores on the pain scale of the Health Assessment Questionnaire was 0.33 with acetaminophen (95 percent confidence interval, 0.14 to 0.52), 0.30 with the low dose of ibuprofen (95 percent confidence interval, 0.09 to 0.51), and 0.35 with the high dose of ibuprofen (95 percent confidence interval, 0.13 to 0.57). Side effects were minor and similar in all three groups.

Conclusions: In short-term, symptomatic treatment of osteoarthritis of the knee, the efficacy of acetaminophen was similar to that of ibuprofen, whether the latter was administered in an analgesic or an antiinflammatory dose.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetaminophen / therapeutic use*
  • Chronic Disease
  • Double-Blind Method
  • Female
  • Humans
  • Ibuprofen / administration & dosage*
  • Ibuprofen / therapeutic use
  • Knee Joint*
  • Locomotion
  • Male
  • Middle Aged
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / physiopathology
  • Pain
  • Range of Motion, Articular
  • Surveys and Questionnaires


  • Acetaminophen
  • Ibuprofen