Increased Incidence of Melanoma in Rheumatoid Arthritis Patients Treated With Methotrexate

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Title: Increased Incidence of Melanoma in Rheumatoid Arthritis Patients Treated With Methotrexate
URL: http://www.pslgroup.com/dg/222F6A.htm
Doctor's Guide
June 4, 2008

HOBOKEN, NJ -- June 4, 2008 -- Findings of a recent study in Australia suggest an increased risk of melanoma, as well as other malignancies, for rheumatoid arthritis (RA) patients receiving methotrexate. Results of this study are featured in the June 2008 issue of Arthritis Care & Research.

The study focused on 459 RA patients in Melbourne, Australia. All started treatment with methotrexate prior to June 1986. The majority had no previous history of immunosuppressant therapy and 61% were rheumatoid factor positive. Researchers set out to determine the cancer incidence in these patients compared with the general population and compared with the results of published studies on the incidence of malignancy in methotrexate-treated RA populations in other countries. For all patients, follow-up started on the date they first started methotrexate therapy and ended on the date of their last confirmed doctor visit or death. Over the total of 4,273 person-years of follow-up there was an average of 9.3 years per patient and 87 identified malignancies.

Researchers then compared the cancer incidence observed among these RA patients with that of their healthy peers in Victoria, Australia. Standard incidence ratios for all malignancies and for selected cancers were calculated using state population cancer rates, stratified by sex, age, and calendar years, from 1983 to 1999. Cox regression analysis was also performed, including positive rheumatoid factor and every use of 2 immunosuppressive agents, azathioprine and cyclophosphamide.

RA patients exposed to methotrexate were found to have an estimated 50% excess risk of developing cancer in any form. The risk of non-Hodgkin's lymphoma was more than 5 times higher in RA patients than in the general population. RA patients also had a 3-fold increased risk of melanoma and almost a 3-fold increased risk of lung cancer.

While the increased risk levels 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 as novel. "This study is, to our knowledge, the first to report an increased risk of melanoma in patients with RA treated with methotrexate compared with the general population," notes its lead author, Rachelle Buchbinder, MD, Monash University, Victoria, Australia.

Interestingly, the researchers observed a 2.5-fold increased cancer risk for methotrexate-treated RA patients exposed to cyclophosphamide, but contrary to expectation, no increased risk with exposure to azathioprine.

Despite its limitations, lack of an RA control group that was not exposed to methotrexate, for one, this study has important implications, particularly in regard to the risk of melanoma for RA patients. "Further investigation is needed to determine whether this risk is unique to Australia and what role methotrexate, immunosuppression per se, and/or environmental factors such as exposure to UV radiation play in its development," Dr. Buchbinder stresses. "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."

SOURCE: Wiley-Blackwell Publishing

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