Cyclosporine and PUVA clearly increase the risk of squamous cell carcinomas, and there is evidence that TNF blockers and methotrexate may do so to a lesser degree. UVB phototherapy has not been shown to cause skin cancer. Acitretin offers protection against the development of basal cell and squamous cell carcinomas.
Certain psoriasis therapies contribute to the development of skin cancers, while other treatments protect against skin cancers, and still others have not been shown to increase or reduce skin cancers.
“Since the description of psoriasis, it has been known that sun exposure makes the disease better, but it also causes skin cancers,” says Mark Lebwohl, M.D., a professor and chair of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City.
In an interview with Dermatology Times, following his presentation on psoriasis at the American Academy of Dermatology (AAD) annual meeting in March, Dr. Lebwohl also notes that when broadband ultraviolet (UV) phototherapy was introduced, “by chance, it omitted most wavelengths under 300 nm, which happen to be the wavelengths that are the most carcinogenic.”
A 25-year review published in the Archives of Dermatology in 1981 reported no increase in skin cancers among patients with psoriasis and atopic dermatitis who were treated with broadband UVB phototherapy.
“You would expect narrowband UVB would be even safer that broadband,” Dr. Lebwohl says. “At least so far, it appears that narrowband UVB does not contribute to skin cancer. Nonetheless, in patients who are cancer-prone, we are cautious about the use of phototherapy.”
On the other hand, PUVA (photochemotherapy) causes a dramatic increase in squamous cell carcinomas, and after many years, an increase in malignant melanomas.
The oral therapy first used for psoriasis was methotrexate.
“Now that we have access to registry data, it appears that the drug does cause an increase in skin cancers, specifically squamous cell carcinoma,” Dr. Lebwohl says.
The transplant drug cyclosporine, which was subsequently introduced for the treatment of psoriasis, “definitely causes an increase in skin cancers,” Dr. Lebwohl adds.
An Australian study published in the journal Transplantation in 1996 found that among kidney transplant patients treated with cyclosporine, the most common cause of death was metastatic squamous cell carcinoma of the skin.
“For transplant candidates who stay on cyclosporine, the frequency of skin cancers keeps rising year after year,” Dr. Lebwohl says. “In fact, in patients who have been on immunosuppressive transplant medication for 20 years, the frequency of squamous cell carcinoma of the skin approaches 50%.”
The next drug introduced to treat psoriasis was the precursor to acitretin, called etretinate.
“That drug has actually been shown to be clearly protective against the development of skin cancers,” Dr. Lebwohl conveys. “Thus, in a patient prone to acquiring basal cells and squamous cells, taking acitretin results in many fewer skin cancers. But once the patient stops taking the retinoid, the skin cancer count rebounds.”
More recently, psoriasis and psoriatic arthritis have been treated with tumor necrosis fibrosis (TNF) blockers: etanercept, adalimumab, infliximab, golimumab and certolizumab.
Long-term registries indicate that TNF blockers “increase the development of squamous cell carcinomas,” Dr. Lebwohl says. “They also appear, although not statistically significant, to cause a striking increase in malignant melanomas.”
The first drug to debut after the TNF blockers is ustekinumab, which blocks two cytokines: interleukin-12 (IL-12) and interleukin 23 (IL-23).
The earliest registries of ustekinumab show there is not an increase in skin cancers.
“There are also people who are born without the molecule that ustekinumab blocks, and they do not develop more skin cancers either,” Dr. Lebwohl says.
Downstream from IL-23 is IL-17, which is blocked by three fairly new FDA-approved drugs: secukinumab, ixekizumab and most recently, brodalumab, which blocks the IL-17 receptor.
“While we do not have a lot of data on these newer medications, there are people born with defects in IL-17, who also do not get increases in skin cancers,” Dr. Lebwohl relates.
The cancer risk or lack of cancer risk for psoriasis therapy carries implications.
“If a patient has had one or two squamous cell carcinomas, or even a very superficial malignant melanoma, any of these drugs are acceptable,” Dr. Lebwohl says.
But if a patient has had a deep malignant melanoma, “I would be cautious about the TNF blockers,” Dr. Lebwohl says. “Instead, that patient would be given either ustekinumab or an IL-17 blocker.”
In the case of a patient with numerous squamous cell carcinomas, Dr. Lebwohl is less inclined to prescribe a TNF blocker.
“I would be more likely to give them acitretin, which has been shown to be protective, and also more likely to give them IL-17 blockers or ustekinumab, because they have not been shown to cause an increase in squamous cells.”
And while Dr. Lebwohl often treats psoriasis patients with UV light, “we do not have data in a specific population of patients who develop lots of skin cancers, so we do not know if it is safe to continue them on phototherapy,” he says.
As researchers continue to pinpoint how little of the immune system actually needs blocking in order to reverse psoriasis, “this has allowed us to create, literally, designer drugs that only block those small parts of the immune system and, therefore, do not contribute to the development of cancers,” Dr. Lebwohl says.
Disclosure: Dr. Lebwohl reports no relevant financial disclosures.