Etanercept RA therapy appears to carry no increased SCC risk

October 21, 2005

New York — Patients who take etanercept for rheumatoid arthritis (RA) for up to five years bear no increased risk of cutaneous squamous cell carcinoma (SCC), according to a recent study.

New York - Patients who take etanercept for rheumatoid arthritis (RA) for up to five years bear no increased risk of cutaneous squamous cell carcinoma (SCC), according to a recent study.

"One of the concerns ... is that immunosuppressive drugs such as cyclosporine are known to cause a marked increase in SCCs of the skin," says Mark Lebwohl, M.D., professor and chairman, department of dermatology, Mount Sinai School of Medicine, New York, and lead researcher on the study (Arch Dermatol. 2005;141:861-864.). "In fact, there are reports of SCCs starting in patients who are being treated with etanercept."

However, he tells Dermatology Times, "The reports are few and far between. And the drug has been used for years for RA. That's unlike our experience with cyclosporine, where within a couple years we observed enormous numbers of SCCs in patients who had been treated with PUVA, Grenz ray therapy or any kind of treatment that predisposes to SCC. If we suddenly put those patients on cyclosporine, we would see an eruption of SCC. We are not seeing that with etanercept."

Dr. Lebwohl and colleagues examinated clinical trial databases, which included a total of 1,442 patients with a combined 4,257 patient-years of etanercept exposure (median exposure, 3.7 years; maximum exposure, 5.7 years). In this database, 76.5 percent of patients were female, 87.4 percent were white, and patients' mean age was 49.9 years. The postmarketing database included more than 125,000 patients with more than 250,000 patient-years of exposure.

Researchers compared SCC rates in these populations to expected rates gleaned from SCC incidence rates in Arizona (Harris RB, Griffith K, Moon TE. J Am Acad Dermatol 2001;45:528-536.) and Minnesota (Gray DT et al. Arch Dermatology 1997;133:735-740.), which were age- and sex-adjusted to the clinical trials and postmarket study populations.

"It wasn't really a retrospective study because it involved patients in clinical trials," he says.

Before one could comfortably say etanercept poses no increased SCC risk at all in these patients, Dr. Lebwohl says researchers must track for several years the health of psoriasis patients taking this drug whose histories contain factors such as PUVA treatments and heavy sun exposure.

But at this point, he says, "it's at least comforting to know that we're not seeing major outbreaks in patients treated with etanercept."

Only four cases

In the study, researchers noted only four SCC cases in the clinical trials database. In all cases, patients were white and receiving concomitant medications that included corticosteroids, nonsteroidal anti-inflammatory drugs and methotrexate. Based on the Arizona and Minnesota incidence studies, the expected incidences in these samples were 13.1 and 5.9 cases for a similarly sized population, respectively. In the postmarketing surveillance database, researchers uncovered 25 cases of SCC.

"Knowing there's another population out there that has used etanercept for years and can be followed for the development of long-term side effects is not as good as following psoriasis patients" because the population wasn't treated with PUVA or known to incur heavy sun exposure, Dr. Lebwohl allows. "But it's still pretty good that we were able to follow RA patients who were treated years before psoriasis patients were."

Going forward, he says, "Amgen undoubtedly is doing postmarketing surveillance and following psoriasis patients who are in clinical trials. Hopefully, this will yield data on our patients as well. The original clinical trials of etanercept in psoriasis also have not shown any significant outbursts of cutaneous malignancies."

Disclosure: The study was funded by Amgen and its subsidiaries. The company oversaw the design, conduct and collection of study data, but not its analysis and interpretation. Dr. Lebwohl has served as a speaker, consultant and investigator for Amgen.

For more information: http://www.mssm.edu/