No cancer risk seen with topical calcineurin inhibitors for atopic dermatitis
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LOUISVILLE, Ky. — Researchers showed with moderate certainty that topical calcineurin inhibitors did not increase cancer risk when used as a treatment for atopic dermatitis among infants, children and adults, according to study results.
“Atopic dermatitis chronically affects the physical and psychosocial functioning of patients and their caregivers, making safe and effective treatments crucial for optimal atopic dermatitis care,” Derek K. Chu, MD, PhD, FRCPC, assistant professor in the division of clinical immunology & allergy, department of medicine, McMaster University, told Healio. “The topical calcineurin inhibitors — pimecrolimus and tacrolimus — are effective treatments, but prominent labels suggest them as carcinogenic based on very low-quality and nonsystematic data, which has led to hesitancies in using these medications.”
These topical calcineurin inhibitors (TCIs) are used to manage AD, but in 2005 and 2011, the FDA released reviews associating this class of drugs with a .
This FDA evaluation was based on data from animals exposed to supratherapeutic levels of calcineurin inhibitors, data from patients using systemic calcineurin inhibitors following organ transplantation and intense systemic immunosuppression, and data collected from uncontrolled adverse event reporting databases, Chu said.
“Our results, however, examined all randomized controlled trials, comparative studies, and noncomparative studies investigating the use of topical calcineurin inhibitors in patients with atopic dermatitis, and using the structured GRADE system to evaluate the evidence, found likely no increased risk of cancer,” Chu, who is also of the department of health research methods, evidence and impact at The Research Institute of St. Joe's Hamilton, added.
To conduct their study, Chu and colleagues of an American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology Joint Task Force on Practice Parameters conducted a systematic review and Bayesian meta-analysis of 121 published studies. These studies included 52 randomized controlled trials and 69 nonrandomized studies that comprised 3.4 million patients with AD treated with TCIs for longer than 3 weeks. Mean patient follow-up was 11 months (range, 0.7-150).
Results, presented at the ACAAI Annual Scientific Meeting and published in The Lancet Child & Adolescent Health, showed an absolute cancer risk of 4.7 per 1,000 with TCI exposure compared with 4.56 per 1,000 without TCI treatment, suggesting no increase in risk based on moderate-certainty evidence (OR = 1.03; 95% credible interval, 0.94-1.11). Researchers also noted this risk did not appear different than that of the general population, at 4.6 per 1,000.
These findings persisted in analyses evaluating infants, children and adults alone, as well as in trial sequential, subgroup and sensitivity analyses.
“Our findings are consistent with previous findings that show systemic absorption of topical calcineurin inhibitors is below immunosuppressive levels and that patients with atopic dermatitis who use topical calcineurin inhibitors are not immunosuppressed or immunocompromised,” Chu said, adding that these finding support those of long-term studies showing no increased risk for cancer among patients with AD using TCIs.
“While we believe our findings provide actionable information to inform updated guidelines, product labels, and educational programs, they also provide a knowledge synthesis framework to evaluate rare harms of medications,” he added. “One such class of medications that is now gaining new attention for its potential risk for an adverse increase in death and cardiovascular events, cancer and thrombosis are JAK inhibitors.”