Cochrane Summaries

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Non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people taking methotrexate for inflammatory arthritis

Colebatch AN, Marks JL, Edwards CJ
Published Online: 
9 November 2011

This summary of a Cochrane review describes what we know from research about any safety issues from using non-steroidal anti-inflammatory drugs, or NSAIDs, including aspirin, or paracetamol (acetaminophen), or both, along with methotrexate in people with inflammatory arthritis.

The review shows that in people with inflammatory arthritis:

- NSAIDs, including aspirin, plus methotrexate may not increase lung problems in people with rheumatoid arthritis.

- High dose aspirin plus methotrexate may increase liver problems in people with rheumatoid arthritis.

- High dose aspirin plus methotrexate may increase kidney problems in people with rheumatoid arthritis.

- NSAIDs plus methotrexate may cause a brief and mild increase in blood problems (low platelet count) in people with rheumatoid arthritis, particularly if NSAIDs are taken on the same day as methotrexate.

- NSAIDs, including aspirin, plus methotrexate seems not to increase the chance of people with rheumatoid arthritis stopping taking their methotrexate due to side effects.

- No studies were found that looked at paracetamol plus methotrexate.

- No studies were found in people with conditions other than rheumatoid arthritis.

Often we do not have precise information about side effects and complications, particularly for rare but serious side effects. Possible side effects associated with high dose paracetamol includes liver problems. NSAIDs, including aspirin, may cause stomach, kidney or heart problems, and methotrexate may cause stomach problems, liver problems, anaemia or infection.

What is inflammatory arthritis, and what drugs are used to treat pain?

Inflammatory arthritis is a group of diseases that includes rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and other types of spondyloarthritis. When you have inflammatory arthritis, your immune system, which normally fights infection, attacks your joints. This makes your joints swollen, stiff and painful. In rheumatoid arthritis, the small joints of your hands and feet are usually affected first. In contrast, in ankylosing spondylitis the joints of the spine are the most affected. There is no cure for inflammatory arthritis at present, so the treatments aim to relieve pain and stiffness and improve your ability to move.

People with inflammatory arthritis therefore often need to use painkillers, like paracetamol, and NSAIDs such as aspirin or ibuprofen to help ease their pain. Paracetamol, also called acetaminophen, is used to relieve pain but does not affect swelling; non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen, diclofenac and cyclo-oxygenase-2 inhibitors or COX-2s (for example celecoxib), are used to decrease pain and swelling.

Methotrexate is one of the medications most commonly used to treat people with inflammatory arthritis. Methotrexate is a disease-modifying anti-rheumatic drug.  Methotrexate can treat rheumatoid arthritis by decreasing the activity of the immune system. Methotrexate is a common treatment for rheumatoid arthritis and may be prescribed in combination with other drugs, especially for people who are not improving on methotrexate alone. Disease-modifying anti-rheumatic drugs like methotrexate come as tablets, capsules and, in some cases, injections. Unfortunately, there have been some concerns in the past that it may not be safe to use methotrexate at the same time as the painkillers that patients with inflammatory arthritis often need to use.

This record should be cited as: 
Colebatch AN, Marks JL, Edwards CJ. Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis). Cochrane Database of Systematic Reviews 2011, Issue 11. Art. No.: CD008872. DOI: 10.1002/14651858.CD008872.pub2
Assessed as up to date: 
12 May 2010