Do Rheumatoid Arthritis treatments increase cancer risk?

Whether or not biologic drugs increase the risk of cancer in people with rheumatoid arthritis has been the subject of much research and concern in the past few years.

Biologic drugs work by targeting and disabling a specific component of the immune system. Since rheumatoid arthritis is an autoimmune disease, targeting the immune system has been a very effective way of treating the disease. But the question has been, what exactly is the role of the immune system in controlling and fighting cancer? And what happens if we interfere with this function?

We do know that patients with rheumatoid arthritis in general are at higher risk of getting certain malignancies than the general population. Specifically, they are at higher risk of developing lymphoma, leukemia, lung cancer, and skin cancer. Non-Hodgkin lymphoma is the most common malignancy in rheumatoid arthritis patients. This risk is directly related to the degree and duration of inflammation. In other words, the worse the disease, the higher risk of malignancy.

We first started using biologic drugs for treatment of rheumatoid arthritis in 1996. A class of biologic drugs named TNF-inhibitors was the first to be used, and it is still first line biologic treatment for treatment of rheumatoid arthritis. The results have been dramatic, with miraculous improvements in pain, swelling, and prevention of joint deformity.  But in 2003 the FDA noted 6 cases of lymphoma in over 6000 patients that were treated with TNF-alpha inhibitors. The TNF inhibitors available at that time were Enbrel, Humira, and Remicade. So the concern was born:

Do biologic drugs increase risk of cancer in patients with rheumatoid arthritis?

In trying to answer this question, we have learned a few things. First, that almost all the cancers reported in 2003 seemed to have happened in the first year of the TNF inhibitor use. In fact, if one looks at cancer risk over several years, the overall incidence seems to be the same in people who used biologics and those who did not. This can suggest that the drug did not actually cause the cancer, but unmasked the growth of one that was already there, too small to be detected at the time of starting the drug.

Second, if cancer risk is greater in patients with worse rheumatoid arthritis, and these patients were the ones who needed the stronger TNF inhibitor drugs to treat their disease, it is not surprising that they developed the malignancy while those patients with milder disease who did not need the stronger drugs did not.

Finally, the risk of cancer is still very low- both in general population and in patient with RA. This has made investigating the difference between the two groups even more difficult, since most studies of these drugs do not have enough patients developing cancer to power the statistics. So, we have relied on observational studies and metanalyses to answer this question. In fact, there have been multiple such studies in the past few years. And the answer? These studies showed that there is a higher rate of malignancy in patients with rheumatoid arthritis than in the general population; however the risk is the same in patients receiving biologic therapies as those who are not.

The 2012 American College of Rheumatology conclusions on this subject are:

  1. RA patients are at increased risk of lymphoma and lung and skin cancer
  2. Biologic-treated RA patients have similar rates cancer as do non-biologic treated RA patients
  3. RA patients on biologics with a prior history of most cancers are not risk of cancer recurrence


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