Dupilumab not linked to short-term cancer development in patients with atopic dermatitis
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Key takeaways:
- Incidence rates for cancers included 12.88 for the exposed group and 15.04 for the unexposed group.
- Adjusting for immunosuppressant use led to similar hazard ratios without changing the results’ significance.
Patients with atopic dermatitis treated with dupilumab did not experience any significantly increased risk for a primary or recurrent malignancy, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
“A common question that comes up is whether the biologics that we routinely use in clinical practice, such as dupilumab, are safe in this population,” Nicholas Gulati, MD, PhD, assistant professor, The Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, told Healio.
The 5-year retrospective cohort study involved 9,707 patients (6,086 females; mean age, 40 ± 23 years) treated for AD at a single tertiary academic institution between March 28, 2017, and March 28, 2022.
The cohort included 1,627 patients (939 females; mean age, 43 ± 20 years) who received treatment with dupilumab (Dupixent; Sanofi Genzyme/Regeneron). The researchers defined adequate exposure to dupilumab as drug use for at least 2 months.
Also, the researchers considered exposure to at least one of 10 different immunosuppressants for at least 2 months to be a history of immunosuppression, due to the potential cancer-promotive effects of these drugs.
“We were pleased to be able to confirm the safety of dupilumab in the oncology population by showing no association between dupilumab use and cancer development in atopic dermatitis patients,” Gulati, who also is director of the oncodermatology and the early detection of skin cancer clinics at Mount Sinai, said.
“This held true both for patients with and without a history of cancer before starting dupilumab treatment,” he continued.
After analyzing 3,260 dupilumab-exposed and 45,143 unexposed person-years, the researchers found 721 primary malignancies, including 42 among the exposed patients (incident rate [IR] = 12.88; 95% CI, 6.84-22.08) and 679 in the unexposed patients (IR = 15.04; 95% CI, 8.43-24.79; adjusted HR = 1.01).
Keratinocyte cancers such as squamous cell and basal cell carcinomas included 26 in the exposed patients (IR = 7.98; 95% CI, 3.44-15.73) and 451 in the unexposed patients (IR = 9.99; 95% CI, 4.79-18.38; aHR = 0.994; 95% CI, 0.689-1.433).
Nonkeratinocyte cancers included 42 among the exposed patients (IR = 4.91; 95% CI, 1.57-11.54) and 228 (IR = 5.05; 95% CI, 1.65-11.74; aHR = 0.888; 95% CI, 0.537-1.469) among those who were not exposed.
Cancers among patients with a history of malignancy before the study included three in the exposed patients (IR = 0.92; 95% CI, 0.02-5.43) and 37 in the unexposed patients (IR =0.82; 95% CI, 0.01-5.26; aHR = 0.828; 95% CI, 0.249-2.757).
Additionally, the exposed patients had an adjusted hazard ratio of 2.856 (95% CI, 0.994-8.206) of developing cancers in the “other” category, including individual rare cancers, compared with the unexposed patients, with no individual cancer approaching any significant difference between the groups.
There also was no significant difference when all cancers together were compared between the groups, the researchers continued.
The exposure group also totaled 218 patient-years of exposure to immunosuppressants, whereas the unexposed patients totaled 1,393 patient-years. However, the significance of the results did not change after adjustments for immunosuppressant exposure, the researchers said.
Based on these findings, the researchers said they did not find any association between dupilumab treatment for AD and the development of primary or recurrent malignancy, supporting International Eczema Council recommendations for using the drug as first-line therapy for patients with a history of malignancy.
The researchers noted previous studies indicating an association between upregulation of IL-4 and IL-13 with subsequent T helper cell (Th2) polarization with carcinogenesis and modulation of tumor immunosurveillance in most organ systems, whereas dupilumab hampers these cytokines.
While the researchers recognized the theoretical risk for skin-based malignancy development that may come with curbing the Th2 inflammatory cascade with dupilumab, they said their results do not corroborate this risk since the two groups did not display any significant difference in keratinocyte cancers.
However, there was a higher incidence of cutaneous T-cell lymphoma (CTCL) among the exposed patients (IR = 0.92; 95% CI, 0.02-5.43) compared with the unexposed patients (IR = 0.2; 95% CI, 0-4.1; aHR = 3.67; 95% CI, 0.886-15.209) that approached significance, which the researchers said may be an exception that has been echoed by other recent reports.
Considering this potential link between CTCL and dupilumab, the researchers called for more studies evaluating this association, although they also said that patients diagnosed with CTCL may have been misdiagnosed with AD as well, which also has been shown in the literature.
Still, the researchers said, these results demonstrate a lack of association between dupilumab and malignancy over a 5-year period.
“These findings provide reassurance to doctors as they consider the use of dupilumab in patients with a history of or at risk for cancer,” Gulati said.
The researchers plan on continuing their work, Gulati added.
“This study only examined a 5-year period, as that is how long dupilumab had been FDA-approved for atopic dermatitis,” he said. “Confirming lack of cancer risk with long-term dupilumab treatment will require longer follow-up periods.”
For more information:
Nicholas Gulati, MD, PhD, can be reached at Nicholas.gulati@mssm.edu.
Perspective
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While these results are not surprising, it is always significant to confirm hypotheses and reinforce understanding. Dupilumab, like other targeted biologics for AD, has been very impactful not only for its efficacy in treating AD, but also for its relative safety.
Part of its safety has allowed it to be classified as not being an immunosuppressive agent. Because we understand that broad spectrum immunosuppressive agents such as cyclosporine are associated with an increased risk for cancer, to see a lack of association with skin cancer in dupilumab patients over 5 years is extremely reassuring and further cements the notion that it truly is not an immunosuppressive agent.
I am happy to say that I have a large cohort of patients on dupilumab, some for 5 years or more, and this mirrors my experience. I really have not seen an association between an increased risk for skin cancer or other cancers for those patients who are on dupilumab. Of course, my experience is far more limited than what is captured in this study, but it is always reassuring to feel that one’s experience is representative of larger trends.
Perhaps most importantly, this study can be another piece of supporting evidence of the relative safety of this medication. While certainly it is not perfect — there are several known side effects, and some of my patients have had to stop the medication due to issues — most of my patients have seen excellent improvements and have had few side effects, even over extended periods. One of the most common things I hear from patients who were reluctant to start dupilumab but have seen dramatic improvements is “Why did we wait so long to do this?!”
While not glamorous and rarely newsworthy, this type of ongoing monitoring is critical for learning about medications over longer periods of time in larger groups of people. We are still learning about medicines such as aspirin, which has been around for more than 100 years, so continued vigilance is always warranted!
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