Rheumatoid arthritis (RA) patients receiving the tumor necrosis factor (TNF) antagonist etanercept for up to 5 years do not have an increased risk of cutaneous squamous cell carcinoma (SCC), according to new research reported in the July issue of the Archives of Dermatology.¹

Lead researcher Mark Lebwohl, MD, dermatologist at Mount Sinai School of Medicine in New York City, and colleagues reviewed data to determine the incidence of SCC in 1,442 patients with RA comprising 4,257 patient-years of etanercept exposure (with a median exposure of 3.7 years) from an etanercept clinical trials database. The investigators also determined SCC incidence among 125,000 patients with in excess of 250,000 patient-years of etanercept exposure in an etanercept postmarketing database.

Incidence comparable to general population

During the study period, only four cases of SCC were observed in the etanercept clinical trials database-an incidence that compares favorably with the expected rate of occurrence based on general population data from Arizona and Minnesota. Similarly, few cases of SCC (one per 10,000 patient-years) had been reported during postmarketing surveillance of etanercept, the study found.

While "it's too early [to draw any definitive conclusions from these data sets], I certainly don't expect the kind of increase we see with cyclosporine or other immunosuppressive drugs," Dr. Lebwohl tells CIAOMed. The association between immunosuppressive treatments and SCC is well established, he notes. Rapid development of SCC has been well documented in clinical practice among psoriasis patients treated with psoralen-UV-A who are also receiving cyclosporine.

The low incidence of SCC seen in the RA population is not mirrored in patients with psoriasis; however, additional clinical trials with more sensitivity in detecting adverse events associated with agents used in rheumatologic practice may determine if SCC is underreported. In addition, patients with psoriasis may have an even higher risk of skin cancer, due primarily to the use of previous treatments with carcinogenic potential.

"The long-term risk of SCC in patients with psoriasis receiving etanercept is unknown, but future analyses in the psoriatic population with extreme exposure to etanercept will help to answer this question," Dr. Lebwohl and colleagues write.

Going forward, Dr. Lebwohl says that studies should provide "more data that would make us even more secure about using the drugs." It is too early to tell whether these findings extend to other TNF- inhibitors on the market. However, "this data is promising," he adds.

Still some concern

At least one rheumatologist is reserving judgment on TNF- inhibitors and SCC risk. Salahuddin Kazi, MBBS, chief of the section of rheumatology at Dallas VA Medical Center in Texas, tells CIAOMed: "At a brief glance, I am worried about…the short lag period between exposure (etanercept) and cancer. We know the incubation period is longer than that."

Reference:

Lebwohl M, Blum R, Berkowitz E, et al. No evidence for increased risk of cutaneous squamous cell carcinoma in patients with rheumatoid arthritis receiving etanercept for up to 5 years. Arch Dermatol. 2005;141:861-864.