Similar Effects of Exercise Therapy, Nonsteroidal Anti-inflammatory Drugs, and Opioids for Knee Osteoarthritis Pain: A Systematic Review with Network Meta-analysis

J Orthop Sports Phys Ther. 2022 Apr;52(4):207-216. doi: 10.2519/jospt.2022.10490.


Objective: To compare the effectiveness of opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), and exercise therapy for knee osteoarthritis pain.

Design: Systematic review with network meta-analysis.

Literature search: We searched the databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception to April 15, 2021. Web of Science was used for citation tracking.

Study selection criteria: Randomized controlled trials comparing exercise therapy, NSAIDs, and opioids in any combination for knee osteoarthritis pain.

Data synthesis: Network meta-analysis comparing exercise therapy, NSAIDs, opioids, and placebo/control for knee osteoarthritis pain. Additional trials from previous reviews were included to create the external placebo/control anchor.

Results: We included 13 trials (1398 patients) with direct comparisons, supplemented with data from 101 additional trials. The treatment effect of NSAIDs for knee osteoarthritis pain was similar to that of opioids (standardized mean difference [SMD], 0.02; 95% confidence interval [CI], -0.14 to 0.18; Grading of Recommendations, Assessment, Development and Evaluations [GRADE]: low certainty). Exercise therapy had a larger effect than NSAIDs (SMD, 0.54; 95% CI, 0.19 to 0.89; GRADE: very low certainty). No estimate could be made for exercise vs opioids due to the lack of studies. Exercise therapy ranked as the "best" intervention in the network meta-analysis, followed by NSAIDs, opioids, and placebo/control intervention (GRADE: low certainty).

Conclusion: Exercise therapy ranked as the best treatment for knee osteoarthritis pain, followed by NSAIDs and opioids. The difference between treatments was small and likely not clinically relevant, and the overall confidence in the ranking was low. The results highlight the limited evidence for comparative effectiveness between exercise therapy, NSAIDs, and opioids for knee osteoarthritis pain. J Orthop Sports Phys Ther 2022;52(4):207-216. doi:10.2519/jospt.2022.10490.

Keywords: analgesics; knee; osteoarthritis; pain; physiotherapy.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid* / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Exercise Therapy
  • Humans
  • Network Meta-Analysis
  • Osteoarthritis, Knee* / complications
  • Osteoarthritis, Knee* / drug therapy
  • Pain / drug therapy


  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal