Topical Calcineurin Inhibitors Not Linked With Increased Risk of Keratinocyte Carcinoma

Maryam Asgari, MD, MPH

There is no apparent association between topical calcineurin inhibitor exposure and overall keratinocyte carcinoma, basal cell carcinoma, and squamous cell carcinoma among adults with atopic dermatitis.

The findings suggested the use of topical calcineurin inhibitors may be safe with respect to keratinocyte carcinoma among such patients.

Maryam Asgari, MD, MPH, and investigators examined the overall risk of keratinocyte carcinoma as well as by subtype among adults with atopic dermatitis exposed to topical calcineurin inhibitors compared with those exposed to topical corticosteroids and those unexposed to topical calcineurin inhibitors or topical corticosteroids. To do this, the team conducted a retrospective cohort study at Kaiser Permanente Northern California.

The investigators included adult health plan members at least 40 years old who were diagnosed with atopic dermatitis or dermatitis by a clinician between 2002 and 2013 while enrolled at Kaiser Permanente Northern California. Patients needed at least 2 years of continuous health plan membership.

Using National Drug Code and text-string searches, the team collected prescriptions for topical calcineurin inhibitors and topical corticosteroids. Patients were classified into 3 time-varying exposure groups: topical calcineurin inhibitor-exposed, topical corticosteroid only-exposed, and unexposed. The team was specifically interested in the comparison between topical calcineurin inhibitor exposure and topical corticosteroid only-exposed patients.

Length of use was defined as short-term (less than 2 years), moderate-term (2 to less than 4 years), and long-term (4 or more years).

Overall, the team included 93,746 patients with atopic dermatitis—7033 received at least 2 prescriptions for topical calcineurin inhibitors and 73,674 received at least 2 prescriptions for topical corticosteroids. The mean age was 58.5 years old with more women included than men (58.7%).

Using multivariable Cox proportional hazards regression, the team found no association between topical calcineurin inhibitor exposure and keratinocyte carcinoma risk (adjusted hazard ratio [aHR], 1.02; 95% CI, .93-1.13) compared with topical corticosteroid exposure. There was also no significant differences in basal cell carcinoma risk (aHR, 1.01; 95% CI, .9-1.14, topical calcineurin inhibitor vs topical corticosteroids).

When the investigators changed the comparator group to unexposed patients, they achieved similar findings (aHR, 1.04; 95% CI, .91-1.19, topical calcineurin inhibitor vs unexposed for basal cell carcinoma). There were no associations between topical calcineurin inhibitor dose, frequency, and duration of use with basal cell carcinoma, squamous cell carcinoma, or overall risk of keratinocyte carcinoma.

The team said the study was conducted to address safety concerns related to the risk of keratinocyte carcinoma after treatment with topical calcineurin inhibitors. The findings mays add reassurances regarding the safety profile to patients, clinicians, and regulators alike.

The study, “Association Between Topical Calcineurin Inhibitor Use and Keratinocyte Carcinoma Risk Among Adults With Atopic Dermatitis,” was published online in JAMA Dermatology.