Methotrexate for arthritis raises cancer risk
Patients with rheumatoid arthritis who are treated with methotrexate appear to have an elevated risk of developing melanoma.
Patients with rheumatoid arthritis who are treated with methotrexate appear to have an elevated risk of developing melanoma compared with the general population.
Melanoma, the most serious type of skin cancer, also has a greater tendency to spread and is associated with higher mortality rates compared with other types of skin cancer. According to U.S. government statistics reported between 2001 and 2005, the average age at diagnosis was 59 years. Less than 1 percent of cases were diagnosed in patients under 20 years old. The highest rates, at 19.5 percent, were among individuals between 45 and 54 years. Adjusting the data for age, the mortality rate was 2.7 per 100,000 men and women per year. The average age at death was 68 years old.
Methotrexate is considered a second-line therapy for rheumatoid arthritis; it is used when the first-line drugs are not effective. The mechanism of action for this drug in rheumatoid arthritis is not completely understood. It appears to work, at least in part, by altering immunity, which may play a role in rheumatoid arthritis.
Researchers in Australia studied 458 patients with rheumatoid arthritis who started methotrexate therapy before 1986. The medical records showed that 64 malignancies were diagnosed during the follow-up period, which averaged 9 years, and an additional 9 cases were diagnosed after the patients had exited follow-up.
The researchers estimated that there was a 50 percent increase in the risk of this malignancy among the rheumatoid arthritis patients compared with the general population. Methotrexate-treated patients also had five-times the risk of non-Hodgkin's lymphoma, three-times the risk of lung cancer and three times the risk of melanoma. The increased risk of malignancy in general, and of lymphoma and lung cancer in particular, has been previously reported, but the association between methotrexate treatment for rheumatoid arthritis and melanoma is a novel finding.
However, further investigation is needed to determine whether this risk is unique to Australia, along with the role of methotrexate's immune system suppression and environmental factors, such as exposure to UV radiation, the development of this malignancy.
Nevertheless, the findings may support a role for regular skin cancer screening for all patients with rheumatoid arthritis, particularly those receiving immunosuppressive therapy.
Arthritis & Rheumatism
June 2008
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