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Evidence Summary

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Key messages from scientific research that's ready to be acted on

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In people with knee osteoarthritis, most NSAIDs, intra-articular hyaluronic acid, and intra-articular corticosteroids reduce pain more than acetaminophen. Hyaluronic acid is better than some NSAIDs.

Bannuru RR, Schmid CH, Kent DM, et al. Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis. Ann Intern Med. 2015;162:46-54.

Review question

In people with knee osteoarthritis (OA), are some drugs better than others for reducing pain and stiffness and improving physical function?

Background

OA is a disease of the joints and often occurs in knees. It develops when your joints lose the cartilage that protects the ends of your bones. There is no cure and it often gets worse over time. Symptoms of knee OA include pain, stiffness, and worsening physical function.

There are different treatments for the symptoms of knee OA. This review is about drugs given by mouth (oral method) or by injection directly into the knee joint (intra-articular [IA] method) to reduce symptoms.

How the review was done

The researchers did a systematic review, searching for studies that were published up to August 2014.

They included 137 randomized controlled trials with 33,243 people (average age 45 to 76 years, 3% to 100% women).

The key features of the studies were:

  • people had knee OA, with symptoms such as pain and stiffness;
  • drugs used were oral acetaminophen; oral nonsteroidal anti-inflammatory drugs (NSAIDS) including celecoxib, diclofenac, ibuprofen, and naproxen; IA corticosteroids; and IA hyaluronic acid;
  • most drugs were compared with placebo; some were compared with each other; and
  • people were followed for 3 months.

What the researchers found

Compared with placebo:

  • oral acetaminophen, oral NSAIDs, IA corticosteroids; and IA hyaluronic acid reduced pain;
  • oral acetaminophen, oral NSAIDs, and IA hyaluronic acid improved physical functioning; and
  • oral NSAIDs and IA hyaluronic acid reduced stiffness.

Compared with acetaminophen:

  • diclofenac, ibuprofen, naproxen, IA corticosteroids, and IA hyaluronic acid reduced pain; and
  • oral NSAIDs improved physical functioning and reduced stiffness.

IA hyaluronic acid reduced pain more than celecoxib and naproxen and improved physical functioning more than IA corticosteroids.

There was not enough information to compare the side effects of the drugs.

Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.

Conclusions

In people with knee osteoarthritis, all drugs evaluated in the review reduce pain and most improve physical functioning. Oral NSAIDs, IA hyaluronic acid, and IA corticosteroids each reduce pain more than acetaminophen, and IA hyaluronic acid is better than some NSAIDs.

Oral or IA drugs for knee osteoarthritis

Outcomes

Number of trials (people)

Effect of treatment at 3 months*

Pain

129 trials (32,129 people)

Acetaminophen, NSAIDs†, IA corticosteroids, and IA hyaluronic acid reduced pain more than placebo

 

 

Diclofenac, ibuprofen, naproxen, IA corticosteroids, and IA hyaluronic acid reduced pain more than acetaminophen

 

 

IA hyaluronic acid reduced pain more than celecoxib or naproxen

Physical functioning

76 trials (24,059 people)

Acetaminophen, NSAIDs†, and IA hyaluronic acid improved physical functioning more than placebo

 

 

NSAIDs† improved physical functioning more than acetaminophen

 

 

IA hyaluronic acid improved physical functioning more than IA corticosteroids

Stiffness

55 trials (18,267 people)

NSAIDs† and IA hyaluronic acid reduced stiffness more than placebo

 

 

NSAIDs† reduced stiffness more than acetaminophen

IA = intra-articular; NSAIDs = nonsteroidal anti-inflammatory drugs.

*Trials were combined using a type of analysis that lets you compare treatments even if they were not compared directly in the individual trials.

†Oral NSAIDs include celecoxib, diclofenac, ibuprofen, and naproxen.




Glossary

Placebo
A harmless, inactive, and simulated treatment.
Randomized controlled trials
Studies where people are assigned to one of the treatments purely by chance.
Systematic review
A comprehensive evaluation of the available research evidence on a particular topic.

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