Efficacy and safety of a topical diclofenac solution (pennsaid) in the treatment of primary osteoarthritis of the knee: a randomized, double-blind, vehicle-controlled clinical trial

Arch Intern Med. 2004 Oct 11;164(18):2017-23. doi: 10.1001/archinte.164.18.2017.


Background: Oral nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to relieve the symptoms of osteoarthritis (OA) but can produce harmful systemic effects and end-organ damage. A topical NSAID formulation may provide symptom relief with fewer adverse effects. A new topical diclofenac sodium solution-containing the absorption enhancer dimethyl sulfoxide-was evaluated for the relief of the symptoms of primary OA of the knee.

Methods: A total of 326 patients met entry criteria (including abnormal radiographic findings and flare of pain) and were randomized to receive 40 drops of topical diclofenac solution or a vehicle-control solution, 4 times daily, for 12 weeks. We evaluated 3 primary outcome measures, the Western Ontario McMaster Universities LK3.1 OA Index (WOMAC) pain and physical function subscales and a patient global assessment, and 2 other measures, stiffness and pain on walking, at baseline and after final application. We assessed safety by evaluation of adverse events, vital signs, and irritation at the application site.

Results: Topical diclofenac solution was significantly more effective than the vehicle-control solution for all outcome measures; pain, P = .001; physical function, P = .002; patient global assessment, P = .003; stiffness, P = .005; and pain on walking, P = .004. Among patients receiving topical diclofenac, self-limiting minor skin irritation occurred in 68 (41.5%) of 164 patients, including dryness in 60 (36.6%), rash in 18 (11.0%), and paresthesia, pruritus, and vesiculobullous rash in 1 (0.6%) each. There was no significant difference between groups in NSAID-related gastrointestinal tract complaints or in dropouts due to study-related adverse effects.

Conclusion: Topical diclofenac is effective in the treatment of the symptoms of primary OA of the knee, with only minor local irritation and no significant systemic adverse events.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Diclofenac / administration & dosage*
  • Dimethyl Sulfoxide / administration & dosage
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / drug therapy*
  • Osteoarthritis, Knee / physiopathology
  • Pharmaceutical Solutions / administration & dosage
  • Solvents / administration & dosage
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Pharmaceutical Solutions
  • Solvents
  • Diclofenac
  • Dimethyl Sulfoxide