BRIGHTON, ENGLAND – The risk of cancer is almost 50% higher in people with rheumatoid arthritis who are treated with nonbiologic agents when compared to the general population, according to data just released from the British Society for Rheumatology Biologics Register.
Although the link between rheumatoid arthritis (RA) and malignancy has been previously identified – particularly with respect to a higher risk of non-Hodgkin’s lymphoma (NHL) – these new data from the British Society for Rheumatology Biologics Register (BSRBR) are from a more-contemporary population of patients who have been treated in the era of widespread use of methotrexate (MTX) and other nonbiologic disease-modifying antirheumatic drugs (DMARDs).
Dr. Eric L. Matteson, who is a professor of medicine at the division of rheumatology at the Mayo Clinic, Rochester, Minn., noted in an interview that the registry findings seem to indicate that overall cancer risk is increased in patients with RA and that this risk is similar in patients exposed to biologics and nonbiologics, with the exception that nonmelanoma skin cancer appears to be somewhat more frequent in the biologics treated patients.
"I think the conclusions arrived at are consistent with previous studies and so not surprising regarding nonbiologics, in particular, methotrexate. A study from Australia by Dr. Rachelle Buchbinder, for example, already reported in 2008 an almost identical finding of 50% increased risk of cancer in patients with RA treated with methotrexate."
There was an estimated 50% excess risk of malignancy among RA patients exposed to MTX relative to the general population (standardized incidence ratio, 1.5; 95% confidence interval, 1.2-1.9). In that study, the risk of non-Hodgkin’s lymphoma was more than five times higher in RA patients than in the general population (SIR, 5.1; 95% CI 2.2-10.0). Other cancers for which there was evidence of increased risk were lung cancer (SIR, 2.9; 95% CI 1.6-4.8) and melanoma (SIR, 3.0; 95% CI 1.2-6.2). (Arthritis Care Res. 2008;59:794-9).
Dr. Matteson qualified his remarks by noting that he did not hear the presentation and assumes methotrexate was the comparator drug.
In reporting the findings, Dr. Louise Mercer, a clinical research fellow at the Arthritis Research UK Epidemiology Unit, University of Manchester, England, where the BRSBR is coordinated, on April 13 at the British Society for Rheumatology Annual Conference (Rheumatology 2011;50:iii37-8, abstract OP18) noted that they set a baseline for analyzing the cancer risk of biologic therapy, compared with conventional RA therapy within the BSRBR patient population – the primary reason the register was set up 10 years ago.
The analysis included 3,727 RA patients treated with nonbiologic DMARDS who were enrolled in the register between 2002 and 2008. Data from the national cancer registry for England and Wales provided information about whether or not they developed cancer. SIRs were used to compare the observed vs. the expected number of cancers and were adjusted for age and gender.
Of 148 malignancies occurring in 10,447 patient-years, 128 were solid cancers – including melanoma, and lung, breast, and colorectal cancers – and 20 were hematologic – including NHL and Hodgkin’s lymphoma. The median time from enrollment in the register to cancer diagnosis was 1.3 years, with 52% of patients dying as a result of incident cancer.
The standardized incidence ratio for all cancers was 1.48. Looking at specific types of malignancy, the highest SIR was recorded for NHL, at 3.73, although the risk of lung cancer was also substantial, with a SIR of 2.71. The SIR for colorectal cancer was 0.96.
Considering these findings, "vigilance for cancer, especially lung cancer and lymphoma should be maintained," Dr. Mercer advised.
"Our experience is that all cancers were increased by about 48%, with quite a marked increase in NHL and lung cancer, said Dr. Deborah Symmons, during a separate presentation at the meeting. An interesting finding, she noted, was that any benefit of NSAID drugs used to treat RA in lowering the risk of colorectal cancer appeared to be "wearing off."
Dr. Symmons, also of the Arthritis Research UK Epidemiology Unit in Manchester and a principle investigator for the BSRBR, explained that this adds to the evidence that, "the cancer risk in our general rheumatoid population is increased for some cancers."
These data are of interest, as they will eventually be used to compare the cancer risk of biologic vs. nonbiologic DMARDs. Such analysis is unlikely to be undertaken any time soon, however, as it is planned to occur when 20,000 years of patient follow-up have been accumulated. To date, there has been no signal that an earlier analysis is warranted.