Oakland, CA—As many as 10% of adults in the United States and other industrialized nations suffer from atopic dermatitis, a chronic, pruritic, inflammatory skin disease. While treatment usually involves application of topical emollients and anti-inflammatory agents, such as topical corticosteroids and topical calcineurin inhibitors (TCI), more severe cases often require systemic immunosuppressive therapy.

The FDA has approved two TCIs, tacrolimus and pimecrolimus, but questions have been raised about the long-term safety profile of the newer class of topical agents. Specifically, concerns exist because systemic immunosuppressive medications, including calcineurin inhibitors, have been associated with increased risk of cancer, particularly keratinocyte carcinoma (KC), which consists of squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), according to a report in JAMA Dermatology.

Researchers from Kaiser Permanente Northern California, Massachusetts General Hospital, and Harvard Medical School note that these are the most common cancers in the United States, with a nationwide annual estimated incidence of 5.4 million tumors. Based on published reports indicating a link, the FDA implemented a black box warning for TCIs, citing lack of long-term safety data. 

The current researchers sought to determine if exposure to topical calcineurin inhibitors among adult patients with atopic dermatitis associated with increased keratinocyte carcinoma risk.

In their large, health plan–based cohort study of 93,746 adults with atopic dermatitis, the authors found no increased risk of keratinocyte carcinoma overall among topical calcineurin inhibitor–exposed patients compared with topical corticosteroid–exposed patients or patients unexposed to topical calcineurin inhibitors or topical corticosteroids.

In addition, researchers identified no increased risk when data were examined by subtype of keratinocyte carcinoma—basal cell carcinoma or squamous cell carcinoma.

The retrospective cohort study was conducted at Kaiser Permanente Northern California, a large, integrated healthcare delivery system and included patients who were diagnosed from January 1, 2002, to December 31, 2013. Follow-up continued through December 31, 2017, and data analysis occurred from June 1, 2016, to October 1, 2018. Participants had a mean age of 58.5 years, and most, 58.7%, were women.

Researchers compared time-varying pharmacy-dispensed TCI exposure in 7,033 patients over the study period with topical corticosteroids in 73,674 patients, and no TCI or topical corticosteroid exposure in 46,141.

Findings include:
• Multivariable Cox proportional hazards regression revealed no association between TCI exposure and KC risk (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.93-1.13) compared with topical corticosteroid exposure. 
• No significant differences in BCC risk (aHR, 1.01; 95% CI, 0.90-1.14, TCI vs. topical corticosteroids) or SCC risk (aHR, 0.94; 95% CI, 0.82-1.08, TCI vs. topical corticosteroids) were identified.
• Changing the comparator group to unexposed individuals yielded similar findings (aHR, 1.04; 95% CI, 0.91-1.19, TCI vs. unexposed for basal cell carcinoma). There were no associations between TCI dose, frequency, and duration of use and BCC, SCC, or overall KC risk.

“The results of this postmarketing surveillance study of adult health plan members with AD revealed no apparent association between TCI exposure and overall KC, BCC, or SCC risk,” the authors write. “Secondary analyses examining dose, frequency, and duration of TCI exposure revealed no associations. These findings suggest that use of TCIs may be safe with respect to KC risk among adults with AD.”

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