A chronic, inflammatory disease of unknown origin, rheumatoid arthritis (RA) affects about 1 percent of adults worldwide. Marked by joint destruction, RA often leads to disability and diminished quality of life. It can also lead to an early death from cancer.
Various studies have linked RA to an increased risk of Hodgkin's and non-Hodgkin's lymphoma, leukemia, myeloma, and lung cancer. A link between methotrexate (MTX), a disease-modifying antirheumatic drug (DMARD) commonly prescribed to RA patients, and cancer has also been suggested. Numerous case reports of RA patients treated with MTX developing lymphoma and, even more strikingly, tumors disappearing when the drug was discontinued, have prompted concern that MTX itself may be carcinogenic. So far, however, studies addressing this concern have been inconclusive.
To shed further light on the cancer risk for RA patients treated with MTX, researchers in Australia, where RA affects over 2 percent of adults, studied the cancer incidence in RA patients treated with MTX by local doctors. Their findings, featured in the June 2008 issue of Arthritis Care & Research, suggest an increased risk of melanoma, as well as other malignancies, for RA patients receiving MTX.
The study focused on 459 RA patients, 309 women and 150 men, regularly seen by 1 of 6 rheumatologists based in Melbourne. All had started treatment with MTX prior to June 1986. The majority had no previous history of immunosuppressant therapy. 61 percent 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 MTX-treated RA populations in other countries. For all patients, followup started on the date they first started MTX therapy and ended on the date of their last confirmed doctor visit or death. Over the total of 4,273 person-years of followup, an average of 9.3 years per patient, 87 malignancies were identified.
Researchers then compared the cancer incidence observed among these RA patients with that of their healthy peers in Victoria, Australia. Standard incidence ratios (SRIs) for all malignancies and for selected cancers were calculated using state population cancer rates, stratified by sex, age (in 5 age groups: under 40, 40-49, 50-59, 60-69, and 70 and over), and calendars years, from 1983-1999. Cox regression analysis was also performed, including positive rheumatoid factor and ever use of two immunosuppressive agents, azathioprine and cyclophosphamide.