Weighing the risks: Biologics used to treat rheumatoid arthritis pose minimal cancer threat

September 1, 2008

A large observational study shows a risk of melanoma and nonmelanotic skin cancer associated with biologic use for rheumatoid arthritis; however, this risk is slight, the study's lead author says.

Key Points

Wichita, Kan. - A large observational study shows increased risks of melanoma and nonmelanotic skin cancer for patients taking biologic drugs for rheumatoid arthritis (RA), but its lead author says the risks are slight.

To assess the association between biologic treatments and malignancies, researchers gathered data on nearly 14,000 patients enrolled in the National Data Bank for Rheumatic Diseases (NDB), who completed semiannual questionnaires between 1998 and 2005.

Study details

"We didn't find associations between the use of biologic therapies and malignancies, with the exception of skin cancer," says Frederick Wolfe, M.D., National Data Bank director and clinical professor of internal medicine at the University of Kansas School of Medicine.

However, he says the study's results weren't surprising in light of existing research in other settings.

Researchers compared cancer rates in their study population with population rates using the U.S. National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database.

Additionally, they used conditional logistic regression to calculate odds ratios (ORs) to estimate the risk associated with biologic therapy.

Researchers, furthermore, adjusted relative risks for six cofounders: age, sex, education level, smoking history, RA severity and prednisone use.

Mean patient age at the time of entry into the study was 58.5 ± 13.1 years, with non-Hispanic whites constituting 92.5 percent of the sample. Men comprised 22 percent of the sample.

More than half of patients (56.4 percent) had a history of smoking, while 45.6 percent were receiving prednisone.

The breakdown of biologic use among patients was as follows:

Mean duration of treatment ranged from nearly three years with infliximab (2.9 years; range: 0.5 to 7.8 years) and etanercept (2.7 years; range: 0.5 to 7.7 years) to 1.2 years with adalimumab.

Results

Overall, researchers observed no increase in the overall rate of cancer in participating patients compared with SEER data.

However, Dr. Wolfe says, "The odds ratio was 1.5 for nonmelanoma skin cancer and 2.3 for melanoma (95 percent CI).

"These are not great risks," and they're similar to skin cancer risks observed in other populations, such as kidney transplant recipients undergoing profound immunosuppression.

One study limitation was that database reports made it impossible for researchers to differentiate between basal cell carcinoma and other forms of nonmelanotic skin cancer, he says.

"So, we don't know what kind of nonmelanotic skin cancer we're dealing with," although researchers didn't consider this a particularly important variable in light of the relatively low risk of such cancers in the sample, Dr. Wolfe tells Dermatology Times.

Similarly, he says because the mean and median exposure to biologics was only three years, it's possible that over a longer follow-up period, the association between malignancy and biologic therapy could grow stronger.

Nevertheless, the authors write that true risk associations regularly appear within three years - even after one year in some post-transplantation studies.

As in any observational study, another potential limitation involves nonrandom assignment to treatment, Dr. Wolfe says.

Essentially, he says, if severe RA cases are more likely to receive biologics, then treatment outcomes are confounded by indication. Therefore, study results could say more about arthritis severity than efficacy of treatment.

However, he says that even if one assumes that malignancies are associated with RA severity and, therefore, with biologic use, researchers would have expected to identify extra malignancies due to this bias. No such increased risk surfaced, though, he says.

For now, he says, "Many clinical trials have shown that biologics are effective therapies."

As such, Dr. Wolfe says, "People must weigh the particular risks that are associated with them."

Disclosure: The NDB has conducted safety registries for Centocor, Sanofi-Aventis and Bristol-Myers Squibb. By contractual agreement with Centocor, this company reviewed the publication's final manuscript.

For more information: http://www.arthritis-research.org/

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