{]"This study is, to our knowledge, the first to report an increased risk of melanoma in patients with RA treated with MTX compared with the general population," concludes lead author Rachelle Buchbinder, MBBS, of Cabrini Medical Centre in Victoria, Australia." Our findings, taken together with other studies investigating the risk of skin cancer in patients with RA, may support a role for regular skin cancer screening for all patients with RA, particularly those receiving immunosuppressive therapy."
The study included 459 RA patients who were regularly seen by one of six rheumatologists. All had started treatment with MTX before June 1986, and most had no previous history of taking immunosuppressive therapy. The follow-up started on the date they first began MTX therapy and ended on the date of their last confirmed doctor visit or death. There were 87 malignancies identified over the total of 4273 person-years of follow-up (with an average of 9.3 years of follow-up per patient).
Researchers then compared the cancer incidence observed among the RA patients with their RA-free counterparts. They calculated standard incidence ratios (SIRs) for all malignancies and for selected cancers with state population cancer rates stratified by sex, age, and calendars years 1983-1999. Cox regression analysis was also performed, including positive rheumatoid factor and ever use of azathioprine and cyclophosphamide.
Increased risk seen for lung cancer, non-Hodgkins as well
RA patients who took MTX were found to have an estimated 50% increased risk of developing any cancer. The risk of non-Hodgkin’s lymphoma was more than five times higher in RA patients than in the general population. RA patients also had a 3-fold increased risk of lung cancer, the study showed.
Although the increased risks for non-Hodgkin’s lymphoma and lung cancer were in line with the findings of related studies in Europe and the United States, the high risk for melanoma stood out. The study found a 2.5-fold increased cancer risk for MTX-treated RA patients who were treated with cyclophosphamide, but no increased risk in those treated with azathioprine.
Is the risk unique to the ‘land down under’?
The study did have several limitations including the lack of an RA control group that was not exposed to MTX. "Further investigation is needed to determine whether this risk is unique to Australia and what role MTX, immunosuppression per se, and/or environmental factors such as exposure to UV radiation play in its development," Dr. Buchbinder stressed.
Translating research into practice
"We would expect some increase in malignancies in patients taking any immunosuppressant drug including biologics; patients with RA already have a known increased risk of lymphoma, and maybe other cancers, without any treatment due to the immune overstimulation [that is a hallmark of the disease]," said Lewis Rosenbaum, MD, vice chief of medicine at William Beaumont Hospital in Royal Oak, Michigan.
The drugs do improve quality of life for millions of RA patients, he told MSKreport.com. Moreover, "it appears that immunosuppressive drugs, particularly MTX, may decrease the risk of cardiovascular disease which is a much more important problem in these patients." It's important that rheumatologists counsel their patients about the risks and benefits of all medications." We know we are using powerful drugs with untoward side effects, but on balance these drugs have greatly improved the quality and quantity of life in these patients."
Reference
1. Buchbinder R, Barber M, Heuzenroeder L, et al. Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate. Arthritis Care Res. 2008;59:794-799.
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