Do Rheumatoid Arthritis Drugs Cause Cancer?

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junkyard transmissionHopefully not.

People often state that drugs used to treat Rheumatoid Arthritis cause cancer as an accepted fact. They say they that shortening the length of life is worth the quality of life they gain from treatment. Personally, I’m tremendously interested in both.

Rheumatoid Arthritis has long been known to increase risk of cancer, especially lymphoma. We know about Rheumatoid heart disease and other things that contribute to the RA mortality gap. Balancing medication risks is a big deal for RA patients: We’d like to know whether our medications are adding to our days or taking away.

If it’s a fact that Rheumatoid Arthritis drugs cause cancer, then why is it so hard to prove?

Because it might not be true. And the problem is very complex.

One reason is the nature of tumor necrosis factor (TNF) which is involved with RA. While one purpose of TNF is to kill tumor cells, it is also multifunctional. TNF is involved in both cell death and cell proliferation! “The dual nature of TNF-a activity may be responsible for its paradoxical anti- and protumor activities depending on the cell, environment, dose, and other factors.”1

RA patients are at higher risk for lymphoma, while lymphoma patients are not at higher risk for RA. And the more severe the RA is, the higher the risk lymphoma. One frequently-quoted study from 2006 says people with severe RA have a 70 fold increased risk of lymphoma.

DMARDs (disease modifying antirheumatic drugs)

Some drugs that are used as DMARDs have been associated with increased cancer risk: azathioprine (Imuran) and cyclophosphamide (Cytoxan). We must remember that an association does not prove causation, but to patients, it may represent risk. Perhaps that is a reason those DMARDs are less frequently used. The most common DMARD, methotrexate, was feared to be associated with increased lymphoma risk about a decade ago, but since then, several large analyses have shown no correlation.

TNF inhibitors

Many of us have read a package insert for a TNF inhibitor, naming cancer as one of the possible risks noted during clinical trials. However, some large studies over the last few years suggest that RA may be more implicated than TNF inhibitors in the increased number of cancer tumors in RA patients.

Here’s an intriguing point: “Also the types of lymphomas observed in patients treated with anti-TNF-a treatment were predominantly B cell lymphomas, similar to that observed in patients with RA, lending support to the hypothesis that these lymphomas were related to the underlying arthritis rather than its treatment. Following this, a meta analysis of 18 studies including 8,808 RA patients by Leombruno did not find an increased incidence of lymphoma or any nonhematologic cancer in patients treated with anti-TNF therapy.”1

However, one 2007 study found that while overall cancer risk was not increased and tumor risk was not greater, skin cancers were increased with Biologic use.2

Recommended reading used as references for this post:

1Downloadable PDF “TNF-α inhibitors: are they carcinogenic?” which is available at this link from Dovepress that was posted by a reader. Go through some of the 53 footnotes about cancer, autoimmune disease, and TNF.

2Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study” on PubMed

2009 Swedish study reported in MedpageToday

Do rheumatoid arthritis and lymphoma share risk factors?: a comparison of lymphoma and cancer risks before and after diagnosis of rheumatoid arthritis” on PubMed

Complications of Anti-TNF Therapies: Do Anti-TNF Drugs Increase the Risk of Malignancies?” on Medscape

Edit 8/17/11: Another article based on a new study of relationship of cancer to several biologics.

More posts on Biologics on RA Warrior:

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Kelly Young. All rights reserved.

This entry was posted on Wednesday, March 30th, 2011 at 6:00 am and is filed under RA Education. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.

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