TOPLINE:

In a comprehensive pharmacovigilance analysis, topical calcineurin inhibitors (TCIs) were not associated with a statistically significant lymphoma safety signal in patients with atopic dermatitis when robust Bayesian methods were applied.

METHODOLOGY:

• The labeling for topical tacrolimus ointment and pimecrolimus cream carries a black box warning for lymphoma in the US, but no longer in Canada.
• To evaluate the risk for lymphoma, the researchers analyzed 56,093,627 adverse drug reactions from 17,448,160 de-duplicated cases submitted to the FDA Adverse Event Reporting System (FAERS) database between January 2014 and March 2025.
• The analysis employed both the reporting odds ratio (ROR) and the empirical Bayes geometric mean (EBGM) statistical methods to evaluate lymphoma-related safety signals across 11 medications used in the treatment of atopic dermatitis.
• Investigators conducted separate analyses for tacrolimus and pimecrolimus, examining both general usage and specific atopic dermatitis indications to determine dosage form and administration route influences on safety signals.

TAKEAWAY:

• RORs suggested elevated lymphoma signals for several drugs, including TCIs, but this method likely overestimated risk for rare events, according to the study authors.
• The EBGM analysis, which is more robust in analyzing rare events like lymphomas, revealed no significant lymphoma-safety signals for topical tacrolimus and pimecrolimus when used specifically for atopic dermatitis.
• Researchers found that EBGM values were significant for systemic medications including azathioprine, mycophenolate mofetil, methotrexate (used to treat certain lymphomas), and all formulations of tacrolimus, but not for TCIs.
• The EBGM value for all formulations of tacrolimus showed no statistical significance when specifically analyzing atopic dermatitis as an indication.

IN PRACTICE:

“While gold standard experimentation methods such as randomized controlled trials are required to confidently disbar the TCI-lymphoma association, this study may help provide reassurance to concerned clinicians in light of related mounting evidence supporting TCI safety,” the study authors wrote. Recent studies, they noted, have “also supported a lack of lymphomagenic potential associated with TCIs.”

SOURCE:

The study was led by Domenico Arcuri, MD, PharmD, McGill University and St. Mary’s Hospital, Montreal, Québec, Canada, and was published online on January 27 in JAAD International.

LIMITATIONS:

The analysis was limited by the impact of drug-drug interactions on adverse drug reaction genesis, potential duplicate reports, and reporting bias.

DISCLOSURES:

The study did not receive any funding. The authors did not declare any conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.