Dupilumab associated with significantly lower malignancy risks in atopic dermatitis
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Key takeaways:
- Researchers compared dupilumab use with other and with no systemic therapy.
- Dupilumab inhibits IL-4 and IL-13, which have been linked to internal tumorigenesis.
Patients who used dupilumab for atopic dermatitis had significantly lower risks for internal malignancies than patients using other therapies, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
Findings were based on data from the TriNetX U.S. Collaborative Network, Nicholas Gulati, MD, PhD, assistant professor, Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, and colleagues wrote.
“There is a growing body of literature suggesting that Th2 cytokines IL-4 and IL-13 are pro-tumorigenic, but most of this work has been done in mice,” Gulati told Healio. “Given that dupilumab inhibits both of these cytokines, we were inspired to see if this medication is cancer-protective in patients.”
Patients had three or more diagnoses of AD between Sept. 21, 2003, and Sept. 21, 2023. The researchers classified patients based on their use of dupilumab (Dupixent; Regeneron, Sanofi) and systemic therapies such as azathioprine, cyclosporine, methotrexate, mycophenolate mofetil and phototherapy.
First, the researchers compared 1,857 patients with severe AD who used dupilumab without any other systemic therapy (average age at dupilumab prescription, 28.54 years; 51.59% female; 49.81% white) with 1,857 patients with mild AD who used non-systemic therapy (average age at third AD diagnosis, 29.72 years; 54.01% female; 50.73% white).
The dupilumab group had significantly lower risks for squamous cell carcinoma and basal cell carcinoma (RR = 0.35; 95% CI, 0.18-0.68) and internal malignancy (RR = 0.47; 95% CI, 0.28-0.78). There were no significant differences between the groups in risks for hematologic malignancy.
Next, the researchers compared 1,378 patients with severe AD who used dupilumab without any other systemic therapy (average age at dupilumab prescription, 32.01 years; 55.44% female; 51.09% white) with 1,378 patients with severe AD who used systemic therapies but not dupilumab (average age at first prescription for systemic therapy, 31.12 years; 53.63% female; 51.67% white).
The dupilumab group had significantly lower risks for internal malignancy (RR = 0.45; 95% CI, 0.27-0.74) and for hematologic malignancy (RR = 0.37; 95% CI, 0.18-0.76). The researchers noted a trend for decreased risks for squamous cell carcinoma and basal cell carcinoma in the dupilumab group as well (RR = 0.52; 95% CI, 0.26-1.05).
Based on these findings, the researchers concluded that the extended inhibition of Th2 cells that comes with dupilumab treatment for AD does not promote the development of malignancies in the short term.
“It is rare to demonstrate that a medication commonly used in clinical practice can have cancer-protective effects,” Gulati said. “These findings will provide great reassurance to patients and physicians alike as they consider dupilumab.”
Gulati also said that he and his colleagues hope these findings increase awareness of dupilumab’s strong safety profile, particularly pertaining to cancer development.
“Doctors can use these results to reassure patients, especially those who have risk factors for cancer such as family history,” he said.
The researchers also suggested that additional research should assess the development of malignancies in the long term and study how the inhibition of Th2 cells protects patients against tumor development.
“We are interested to see if these findings can be extended to patients receiving dupilumab for indications besides atopic dermatitis,” Gulati said, adding that he and his colleagues as well as other teams also are investigating dupilumab’s safety and anti-tumor efficacy in patients with active cancer.
“In particular, we are examining how dupilumab can synergize with immune checkpoint inhibitors, an increasingly popular method of oncologic therapy that relies on the patient's own immune system to treat cancer,” Gulati said.
For more information:
Nicholas Gulati, MD, PhD, can be reached at nicholas.gulati@mssm.edu.
Perspective
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When it comes to safety, more news is good news, especially for a commonly used treatment for a common disease. In this retrospective analysis of a large U.S. database, internal, hematologic and basal cell carcinoma/squamous cell carcinoma malignancy rates were not increased in patients with atopic dermatitis receiving treatment with dupilumab. In fact, in some cases, the relative risk for malignancy appeared reduced.
While there are several caveats to these findings (among others, the retrospective study design, low number of tracked outcomes, limited granularity in malignancy classification and short duration of follow-up) that should make one interpret these findings with caution and not tout dupilumab as an anti-cancer therapy, these data should be reassuring to health care providers and assist in patient counseling.
Future studies would benefit from long-term, prospective evaluation, especially in populations at risk, to truly understand how dupilumab affects malignancy risk.
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