Topical Calcineurin Inhibitors, Keratinocyte Carcinoma, and Risk in Atopic Dermatitis

atopic dermatitis
Woman checking the hand with very dry skin and deep cracks
Investigators sought to assess the overall keratinocyte carcinoma risk and by subtype in adults with atopic dermatitis exposed to topical calcineurin inhibitors.

Use of topical calcineurin inhibitors (TCIs) may be safe regarding the risk for keratinocyte carcinoma (KC) in adults with atopic dermatitis (AD), according to study findings published in JAMA Dermatology.

Investigators sought to assess the overall KC risk and by subtype—basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)—in adults with atopic dermatitis exposed to TCIs, compared with patients exposed to topical corticosteroids (primary comparator group) and those unexposed to TCIs or topical corticosteroids (alternative comparator group), as well as alterations in risk with TCI dose, frequency, and duration of exposure. TCIs primarily used to treat patients with AD have a black box label warning about the potential for increased risk for skin cancer.

The retrospective cohort study included 93,746 adults aged 40 years or older (mean [SD] age, 58.5 [12.7] years; 58.7% women) who were diagnosed with AD or dermatitis from January 1, 2002, to December 31, 2013, and follow-up occurred through December 31, 2017. The researchers compared time-varying pharmacy-dispensed TCI exposure (n = 7033) with topical corticosteroids (n = 73,674) and no TCI or topical corticosteroid exposure (n = 46,141).

With use of multivariable Cox proportional hazards regression, the study authors found no association in TCI exposure and KC risk (adjusted hazard ratio [aHR], 1.02; 95% CI, 0.93-1.13), compared with topical corticosteroid use. In addition, 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 observed. Similar results were obtained when the comparator group was changed to unexposed participants (aHR, 1.04; 95% CI, 0.91-1.19, TCI vs unexposed for BCC). No associations were found in TCI dose, frequency, and duration of use and BCC, SCC, or overall KC risk.

The investigators noted several study limitations, including the observational design. Also, the study relied on pharmacy-dispensed medications rather than self-reported use to characterize exposure, and they were unable to completely account for potential screening biases.

“We noted no increased risk of KC overall or by tumor subtype with TCI use among a large cohort of adults with atopic dermatitis,” stated the study authors. “Our findings appear to support those of smaller postmarketing surveillance studies of TCI and KC risk and may provide some reassurance about the safety profile of this class of topical agents in the treatment of AD.”

Disclosures: One of the authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Asgari MM, Tsai A-L, Avalos L, Sokil M, Quesenberry CP.. Association between topical calcineurin inhibitor use and keratinocyte carcinoma risk among adults with atopic dermatitis [published online August 12, 2020]. JAMA Dermatol. doi: 10.1001/jamadermatol.2020.2240