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Carol Eustice

Rheumatoid Arthritis Drug Methotrexate Raises Cancer Risk

By June 22, 2008

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Methotrexate has been tied to an increased risk of melanoma, as well as other malignancies, for rheumatoid arthritis patients treated with the medication. An Australian study compared 459 rheumatoid arthritis patients (309 women and 150 men who started taking methotrexate before June 1986) to the general population to determine cancer risk.

According to study results, published in the June 2008 Arthritis Care and Research, rheumatoid arthritis patients who were treated with methotrexate were found to have a 50% increased risk of developing any form of cancer. The risk of non-Hodgkins lymphoma was more than 5 times greater in rheumatoid arthritis patients than in the general population. Rheumatoid arthritis patients also were found to have triple the risk of lung cancer and triple the risk of melanoma.

The findings for non-Hodgkins lymphoma and lung cancer agreed with findings from other previous related studies. However, this was thought to be the first study that reported an increased risk of melanoma in rheumatoid arthritis patients treated with methotrexate when compared to the general population. Researchers need to further study whether the findings are unique to Australia and its environmental factors. If further studies confirm a risk of melanoma with methotrexate use, perhaps skin cancer screenings (especially for rheumatoid arthritis patients taking disease-modifying anti-rheumatic drugs like methotrexate) will become an important consideration. According to rheumatologist Scott J. Zashin MD, "Because the rheumatoid arthritis patients were on methotrexate, one does not know if the increased risk was due to rheumatoid arthritis or that the patients were on methotrexate. There are signals that indicate an increased risk of melanoma exists with the TNF blockers (Enbrel, Remicade, and Humira). Hopefully more research will clarify that. Until then, it is good idea for rheumatoid arthritis patients to get a regular skin exam."

In addition to treating rheumatoid arthritis, methotrexate is a treatment option for other conditions including:

The medicine is available as an injectable solution or as oral tablets. Methotrexate injection is given under the skin (subcutaneously). Oral methotrexate is available in 2.5 mg tablets. It's important to remember that the drug is administered once a week for arthritis. The medicine is not taken daily like most medications.

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Photo © Gold Standard

August 5, 2008 at 3:18 pm
(1) Rheum Girl says:

As a person practicing in the field of Rheumatology I find it unprofessional that you would refer to a study without providing a citation. Thanks to this blog my patients are asking to discontiue their methotrexate and put their treatment into jeopardy. Any study that only examines 459 people has poor quality control and oftentimes reports skewed results!! Please think twice before scaring my patients without all the proper information.

August 6, 2008 at 5:05 am
(2) Carol says:

There was a citation listed …published in the June 2008 Arthritis Care and Research. Also, Dr. Zashin’s comment suggested the need for more research. No matter what the news story or study results, patients should not get geared up about discontinuing a treatment without talking to their own doctor.

August 6, 2008 at 5:55 pm
(3) Jeanne says:

FYI, I’ve been on methotrexate for many years,
10-12, and I just recently was diagnosed with my first melanoma. This happened right around the time that the news came out about the study done in Australia. My first reaction was to stop the methotrexate, plus my RA Dr. stopped my Remicade. Not sure what I will try next, but getting the diagnosis of melanoma surely gave me reason to suspect my use of Methotrexate.

March 13, 2012 at 4:30 pm
(4) Christine,UK says:

My mother died of Adenocarcinoma of the lung with metastasis to the liver 3 years ago. She had been a smoker (5 a day) until she was around 60 years of age and then gave up and was a non smoker up to hear death at 83 years. She was diagnose with Rheumatoid Arthritis also at around 60 years. As the disease became more difficult to control her consultant recommended taking Methotrexate. It would be fair to say that the drug controlled the condition for the six years leading up to my mother’s death.
It was suggested at first that the Adenocarcinoma developed due to smoking in earlier years but it should also be noted that this type of cancer is more common in women and non smokers, and in my mother’s case the tumour that covered a sixth of her lung when she died was estimated to have started six years before her death at exactly the time when the Methotrexate was initiated.

Coincidental or not, further research is needed as patients and their families are not always fully aware of the implications of using this drug.

May 16, 2013 at 1:17 pm
(5) Chrissy says:

My husband took this medication 11 years ago when he hurt his back. For some reason the consultant thought it would help as he believed he had arthritis, he was 44 years old and never had any indication of arthritis previous to hurting his back.
He became so ill, white, weak and unwell whilst taking this that he stopped it after about 3 – 4 weeks. After this he developed hypothyroidism, poor responses to flu like illnesses, fibromyalgia and various other issues, such as sore eyes, sensitivity to cold and depression.
He recently was diagnosed with cancer of the throat and neck, and following a 7 hour op, an extremely competent and skilled surgeon removed all the tumours.
I strongly believe this was triggered by the methotreaxate. I have no qualms, as in the comment further up, in noting this as a significant factor in my husband’s illness and feel other’s should be aware.

August 13, 2013 at 5:05 pm
(6) olinlowes says:

Was only on low doses of methotrexate (10 mg week for 4 months) along with 10 mg of prednisone for autoimmune urticaria (hives). After reading the warning labels, I was always suspicious. Two weeks ago, my dermatologist did a biopsy of a flair on my neck. We were actually looking to rule out vasicular urticaria when he did the biopsy. Today, he called me and told me it was skin cancer. I was so upset that I didn’t ask what type it was (he did mention that it was a slow growing type). I have an appointment with him tomorrow and I’ll definately ask what kind. BTW, I stopped the methotrexate and will be scheduling my next appointment at the MD Anderson Cancer Center.

February 23, 2014 at 9:09 pm
(7) Ruben says:

i’m not a professional or anything, I’m just a student. But doesn’t Methotrexate inhibit the enzyme DHFR (Dihydrofolate Reductase) which is needed for cancer cells to actually divide in the first place?

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