CANCER RISK WITH TOPICAL PIMECROLIMUS AND TACROLIMUS FOR ATOPIC DERMATITIS: SYSTEMATIC REVIEW AND BAYESIAN META-ANALYSIS

Abstract

<h3>Introduction</h3> Atopic dermatitis (AD) affects millions worldwide and is effectively managed by topical treatments, including the topical calcineurin inhibitors (TCIs), pimecrolimus and tacrolimus. In 2005 and 2011, the FDA released reviews associating TCIs with theoretical cancer risk, albeit with uncertainty. We systematically reviewed the cancer risk in patients with AD exposed to TCIs. <h3>Methods</h3> The AAAAI/ACAAI Joint Task Force on Practice Parameters systematically identified randomized controlled trials (RCT), comparative, and non-comparative non-randomized studies (NRS) from inception to June 6, 2022, from MEDLINE, EMBASE, GREAT, LILACS, ICTRP, FDA, EMA, company registers, and relevant citations. We included studies in any language addressing the risk of cancer in patients with AD exposed to TCIs for greater than 3 weeks. We excluded split-body studies. We conducted a random-effects Bayesian meta-analysis and used GRADE to rate the certainty of evidence. A multidisciplinary panel including patient partners determined thresholds for important risks. <h3>Results</h3> We analyzed 121 studies (52 RCT, 69 NRS) including 3.4 million patients followed for a mean of 11 months (range 0.7–150). The absolute risk of any cancer with TCI exposure was neither different from controls (absolute risk: 4.70 per 1000 with TCI, versus 4.56 per 1000 without; odds ratio: 1.03 [95%CrI 0.94–1.11], moderate-certainty evidence), nor the general U.S. population (4.6 per 1000). Findings were similar in infants, children, and adults, and were robust to trial sequential, subgroup, and sensitivity analyses. <h3>Conclusion</h3> Among infants, children, and adults with AD, moderate-certainty evidence shows that TCIs are not associated with increased cancer risk. These findings support the safe use of TCIs in the management of patients with AD.