Among the 4 high-quality and 3 moderate quality studies that met the inclusion criteria, oral acetaminophen consistently improved pain and function compared to controls in the treatment of osteoarthritis of the knee (Herrero-Beaumont 2007; Doherty 2011; Reed 2018; Prior 2014; Micelli 2004; Pincus 2004; Altman 2007). The meta-analysis of oral acetaminophen compared to controls demonstrated a meaningful reduction in pain and improved function with no evidence of confounding heterogeneity. Overall, acetaminophen is considered a safe medication with no evidence of significantly increased adverse events among the included studies. However, the United States FDA has a black-box warning for acetaminophen secondary to concern of overdose leading to hepatoxicity or death. When oral acetaminophen was compared to NSAIDs, the use of oral NSAIDs provided a significant reduction in pain and improved function. As a result, providers may consider using oral NSAIDs instead of acetaminophen when a contraindication to oral NSAIDs does not exist in the patient.
Benefits/Harms of Implementation
Although oral acetaminophen is widely used to treat osteoarthritis of the knee, providers must recognize the specific risks associated with each medication. Specific patient contraindications to need to be assessed in an individual basis (Example: patient with renal failure).
Outcome Importance
The most important consideration will be removal of oral narcotics from the medications prescribed in the treatment of osteoarthritis of the knee. This becomes particularly significant due to the rise of the opioid epidemic in the United States.
Cost Effectiveness/Resource Utilization
Evidence based decision making in selecting the optimal systemic treatment for the treatment of symptomatic knee osteoarthritis should result in improved pain and function. For a given systematic treatments as effectiveness increases without raising the risk of adverse events so will its cost effectiveness. To date, the most cost-effective systemic treatment is still to be determined.
Acceptability
Currently acetaminophen is commonly utilized approach in treating symptomatic knee osteoarthritis, hence there should be no issues implementing this recommendation as it does not influence a major change in clinical practice, and it provides further evidence to support and guide these practices.
Feasibility
This recommendation may be implemented immediately having a potential positive impact in clinical practice.
Future Research
Most important future research will provide high quality investigation through either prospective randomized trials or prospective cohort studies to establish efficacy within specific subgroups and populations to tailor systemic medications increasing efficacy and decreasing risk of adverse effects.
- Altman, R. D., Zinsenheim, J. R., Temple, A. R., Schweinle, J. E. Three-month efficacy and safety of acetaminophen extended-release for osteoarthritis pain of the hip or knee: a randomized, double-blind, placebo-controlled study. Osteoarthritis and Cartilage 2007; 4: 454-461
- Doherty, M., Hawkey, C., Goulder, M., Gibb, I., Hill, N., Aspley, S., Reader, S. A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain. Annals of the Rheumatic Diseases 2011; 9: 1534-1541
- Prior, M. J., Harrison, D. D., Frustaci, M. E. A randomized, double-blind, placebo-controlled 12 week trial of acetaminophen extended release for the treatment of signs and symptoms of osteoarthritis. Current Medical Research & Opinion 2014; 11: 2377-87
- Reed, K., Collaku, A., Moreira, S. Efficacy and safety of twice daily sustained-release paracetamol formulation for osteoarthritis pain of the knee or hip: a randomized, double-blind, placebo-controlled, twelve-week study. Current Medical Research & Opinion 2018; 4: 689-699
- Herrero-Beaumont G, Ivorra JA, Del Carmen Trabado M, Blanco FJ, Benito P, Martín-Mola E, Paulino J, Marenco JL, Porto A, Laffon A, Araújo D, Figueroa M, Branco J. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as a side comparator. Arthritis Rheum. 2007 Feb;56(2):555-67. doi: 10.1002/art.22371.
- Miceli-Richard, C., Le Bars, M., Schmidely, N., Dougados, M. Paracetamol in osteoarthritis of the knee. Annals of the Rheumatic Diseases 2004; 8: 923-930
- Pincus T, Koch G, Lei H, et alPatient 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. Annals of the Rheumatic Diseases 2004;63:931-939