Long-Term Data Shows No Increase in Cancer Cases f

Newswise — Data from one large U.S. registry indicate that biologic therapy does not appear to increase overall risks of cancers other than skin cancers in patients with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Washington, DC.

Genetically-engineered biologic agents are often prescribed to counter abnormalities in the immune system that can cause joint inflammation. Typically, however, biologics such as adalimumab, etanercept, infliximab, anakinra and abatacept, are used only as a second line therapy because of their costs as well as possible side effects. Most significantly, concern centers on the perceived added risk for serious infections and cancers as biologic agents are used to treat rheumatoid arthritis.

To assess these possible risks, researchers studied 13,000 individuals participating in the National Data Bank of Rheumatic Disease between 1998 and 2005. Participants reported on all drug use, including biologics, as well as all cancers semi-annually. Of these, 48% had taken biologics. Those reporting new cases of non-melanotic skin cancer totaled 623, while 537 new cases were reported for other cancers.

Comparing these cases with the National Cancer Institute's SEER Database, which tracks cases across the general population, researchers found an increased risk for new melanoma and non-melanotic skin cancer cases in those using biologics. However, there were no significant differences in the risks for all other cancers in this population. Longer follow-up may be required to be certain of the non-association of biologic therapy and tumors other than skin cancers.

"These reports, which confirm registry data studies conducted in Europe, offer valid measurements of cancer rates in rheumatoid arthritis," explains Frederick Wolfe, MD, Project Director, National Data Bank for Rheumatic Disease, Wichita, Kansas, and an investigator in the study. "While longer follow-up may be required, this data shows the use of biologic therapy is not associated with increased risks of lymphoma, lung cancer or other cancers among those with rheumatoid arthritis."

The American College of Rheumatology is the professional organization for rheumatologists and health professionals who share a dedication to healing, preventing disability and curing arthritis and related rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.

Presentation Number: 1321

The Association of New Cases of Cancer with Biologic Therapy

Frederick Wolfe, Kaleb Michaud. National Data Bank for Rheumatic Diseases, Wichita, KS

PURPOSE. Some studies of biologic therapy in randomized trials have suggested the possibility of an increase in lymphoma and/or lung cancer among persons with rheumatoid arthritis (RA) treated with biologics. Possible mechanisms include induction of lymphomas and acceleration of latent solid tumors. However, the number of cases in individual trials is small and confounded by differential severity. We used a longitudinal RA registry to compare biologic and non-biologic users with respect to cancer development.

METHODS. We studied incident cases of cancer among 13,001 subjects participating in a study of RA outcomes during 49,000 patient years of observation and 13 semiannual assessments in the years 1998-2005. Cancer reports were validated by hospital, physician and death records, except for non-melanotic skin cancer that was based on self-report and follow-up interview. Subjects were characterized as ever or never users of biologic therapy prior to the development of the cancer or the end of the follow-up period, and then further characterized by duration of individual biologic and total biologic use. Cancer rates were compared with overall population rates using the U.S. National Cancer Institute SEER data bank. Tests of treatment effect used conditional logistic regression to calculate odds ratios as estimates of the relative risk of the various cancers. In addition to conditioning on semiannual entry and exit period, we included six factors as an a priori set of confounders in all models. The included factors were age, sex, education level, smoking history, illness severity and prednisone use.

RESULTS. Biologic use was 48%. There were 623 incident cases of non-melanotic skin cancer and 537 other cancers. The standardized incidence rates (SIR) and 95% CI were: all cancers 1.0 (0.9-1.0), breast 0.7 (0.6-0.9), lung 1.1 (1.0-1.3), colon 0.5 (0.4-0.6), non-Hodgkin's lymphoma 1.6 (1.2-2.1). As shown in Table 1, biologic therapy was unassociated with major cancers, including lung cancer (odds ratio 1.1 (0.7-1.8)) and lymphoma (odds ratio 1.0 (0.5-2.0)). However, melanoma and other skin cancers occurred more frequently among biologic users including users of infliximab and etanercept.

CONCLUSIONS. This report confirms the results of European studies and shows an overall increase in lymphoma and lung cancer and decrease in breast and colon cancer in persons with RA, as well as non-increase when all cancers are considered simultaneously. Biologic therapy was associated with increased rate in melanotic and non-melanotic skin cancer, but not with any other form of cancer, including lymphoma and breast cancer. However, longer follow-up may be required to be certain of the non-association of biologic therapy and tumors other than skin cancers.

Disclosure Block: F. Wolfe, Research support from Amgen, Aventis, Bristol-Myers-Squibb, Centocor, 2; K. Michaud, None.