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Topical calcineurin inhibitors (TCIs) for atopic dermatitis, a.k.a. eczema, did not seem to up the long-term risk for developing skin cancer, according to a manufacturer-sponsored study.

Among nearly 100,000 adults with atopic dermatitis, those treated with a topical calcineurin inhibitor did not see a significantly higher risk for keratinocyte carcinoma (KC) compared with those who received topical corticosteroids (adjusted hazard ratio 1.02, 95% CI 0.93-1.13), according to Maryam Asgari, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues.

Even when broken down by specific keratinocyte carcinoma subtype, topical calcineurin inhibitor treatment wasn't tied to a higher risk for either basal cell carcinoma (BCC, aHR 1.01, 95% CI 0.90-1.14) or squamous cell carcinoma (SCC, aHR 0.94, 95% CI 0.82-1.08), they stated in .

Exposure to topical calcineurin inhibitors also showed no elevated risk for BCC when compared to those not exposed to either treatment, including TCIs or topical corticosteroids (aHR 1.04, 95% CI 0.91-1.19).

And in a secondary analysis, the dosage, frequency of use, and the duration of topical calcineurin inhibitor use had no significant impact on the overall risk for KC. This also held true specifically for both BCC or SCC risk.

Topical calcineurin inhibitors, including Elidel Cream (pimecrolimus) and Protopic Ointment (tacrolimus), currently carry a boxed warning regarding the potential increased risk for cancer issued by the FDA in January 2006. The study was sponsored by Valeant Pharmaceuticals, which sells Elidel Cream.

"A hypothesized mechanism of action for TCIs increasing KC risk includes a direct effect of calcineurin inhibition on DNA repair and apoptosis, which could influence keratinocyte carcinogenesis," Asgari and colleagues explained.

"While that warning had the intent of helping patients and clinicians understand possible risks, it also had the potential for harm owing to unnecessary discontinuation and decreased adherence," pointed out Aaron Drucker, MD, ScM, and Mina Tadrous, PharmD, PhD, both of Women's College Hospital in Toronto, in an .

They stated that bolstering adherence to topical therapy can pose a challenge for clinicians, even for such treatments like topical corticosteroids that have "decades-long safety track records." As a result, such safety warnings on topical medications could lead to undertreatment of atopic dermatitis, and subsequently impairing quality of life for these patients, they explained.

As a result of the boxed warnings on pimecrolimus and tacrolimus, this FDA-mandated, post-marketing surveillance study was designed to assess the long-term risk associated with KC, the cancer in the U.S.

For this retrospective cohort study, Asgari's group looked at adults with a diagnosis of atopic dermatitis or dermatitis at Kaiser Permanente Northern California. All patients were at least age 40, and were followed-up with for a mean of 7.70 years. Over 7,000 were prescribed a TCI, while nearly 74,000 were treated with topical corticosteroids, and the remaining 46,000 had no TCI or topical corticosteroid exposure.

Drucker and Tadrous praised the study for being "well-designed" and "robust," and emphasized that these findings should be reassuring to healthcare providers. They stressed that if any association does exist, its most likely quite small and that skin cancer attributable to TCI use is ultimately rare.

"Clinicians can use this evidence to counsel and reassure patients for whom the benefits of ongoing treatment with TCIs may outweigh the harms," Drucker and Tadrous concluded.

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