Acetaminophen Least Effective Choice for Knee Osteoarthritis


Elham Reshid and Hailemariam Shimelis : Click for the PDF version

Osteoarthritis (OA) is one of the most common forms of arthritis. It is a chronic condition in which the material that cushions the joints, called cartilage, breaks down. This causes the bones to rub against each other, causing stiffness, pain and loss of joint movement. The cause is not fully understood. 1 There is no cure for osteoarthritis, but there are medications to help relieve pain, when needed. Physical therapy (PT) or occupational therapy (OT) may be recommended to help improve strength and function. When pain is severe and frequent or mobility and daily activities become difficult, surgery may also be considered.2

Despite the prevalence of knee OA, few studies compared treatments head-to-head. A meta-analysis that compared 137 reports for common treatments of knee OA according to their relative efficacy was carried out. In this analysis, randomized trials that compared two or more treatments for clinically or radiologically diagnosed symptomatic primary knee OA were included. The included studies tested the oral drugs acetaminophen, celecoxib, diclofenac, ibuprofen, and naproxen; intra-articular injections of corticosteroids or hyaluronic acid; and oral and injected placebo..3

The results revealed that small but robust differences were observed between active treatments. However, acetaminophen (Paracetamol), the most widely used over the counter treatment (OTC), does not provide a clinically significant reduction in pain. Furthermore, Intra-articular (IA) treatments were superior to non-steroidal anti-inflammatory drugs, possibly because of the integrated IA placebo effect.4,5

All treatments relieved some knee OA pain after 3 months compared with oral placebo. Hyaluronic acid was best, with an effect size of 0.63 (95% credible interval, 0.39 0.88).The least effective, acetaminophen, had an effect size of 0.18 (95% credible interval, 0.04 0.33),which did not meet the prespecified boundary for clinical significance. Only slightly more effective than acetaminophen was celecoxib, which was surprising because past studies had demonstrated a greater effect for the cox2 inhibitor.6

In general, the following inferences were made from the analysis:

For relieving pain; injections were more effective than oral treatments, and placebo injections were more effective than oral non-steroidal anti-inflammatory drugs. However, the researchers point out that the apparent superiority of intra-articular treatments may not reflect a placebo effect but, instead, relief from injecting any fluid into the joint space.

For stiffness; naproxen, ibuprofen, diclofenac, and celecoxib were more effective than oral placebo and acetaminophen, and injected hyaluronic acid was better than injected placebo. However, injected placebo was not significantly better than oral placebo.

For function; all interventions except injected corticosteroids were better than oral placebo. Naproxen, ibuprofen, diclofenac, and celecoxib were more effective than acetaminophen. Hyaluronic acid was better than injected placebo or injected corticosteroids. The two types of placebo performed equivalently.

Finally this information, along with the safety profiles and relative costs of included treatments, will be helpful to practicing clinicians for individualized patient care decisions and better rational drug use.


2. Ibid.
3. Ibid. Raveendhara R. Bannuru et al. Ann Intern Med. 2015;162:46-54.
4. Raveendhara R. Bannuru et al. Ann Intern Med. 2015;162:46-54.
5. Ibid.


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