Dupilumab use in atopic dermatitis patients not associated with cancer development

This study, "No association between dupilumab use and short-term cancer development in atopic dermatitis patients," elaborated the findings on atopic dermatitis, dupilumab treatment and malignancy.

Food and Drug Administration (FDA) approved Dupilumab for managing moderate to severe atopic dermatitis (AD). The mechanism of action is related to the inhibition of IL-4 and IL-13 cytokines which are primarily involved in pathways of allergic inflammation.

IgE is prominent in allergic inflammation. Dupilumab reduces TH2-axis activation and decreases IgE levels; due to this property and mechanism of action, it is used in managing AD, asthma, chronic rhinosinusitis, eosinophilic esophagitis, and food allergies.

Though dupilumab use is widespread, there needs to be more data on its use and cancer development. The literature review based on data from the case series and other findings has shown conflicting results regarding malignancy risk with dupilumab.

Considering this background, researchers of the present study investigated the association between Dupilumab and cancer. They used data from AD-treated patients at a single tertiary academic. This record has patients with AD with a cancer ICD code which was thoroughly reviewed.

Records with fewer than three dupilumab medication orders were manually reviewed to confirm initiation and adequate exposure and were classified as drug use for at least two months. Any malignancies diagnosed after these two months of dupilumab therapy were then considered to have occurred in an exposed person.

The researchers calculated cancer incidence rates (IRs) per 1000 person-years of unexposed time versus exposed time (starting from the date of first dupilumab use). Patients were considered to have a history of immunosuppression if they were exposed to at least 1 of the following systemic medications for at least 2 months: cyclosporine, methotrexate, tacrolimus, mycophenolate, azathioprine, upadacitinib, tofacitinib, ruxolitinib, abrocitinib, or baricitinib.

The study results could be summarised as follows:

• There were 9707 AD patients, 6086 females and 3621 males, with a mean age of 40 years.
• Three thousand two hundred sixty dupilumab-exposed and 45,143 unexposed person-years were analyzed.
• Seven hundred twenty-one primary malignancies were reported, with 42 in the exposed and 679 in the unexposed group having IR, 12.88 and 15.04, respectively, with adjusted HR of 1.010.
• Twenty-six keratinocyte cancers (squamous and basal cell carcinomas) in dupilumab-exposed patients versus 451 in unexposed patients with IR, 7.98 and 9.99, respectively and aHR of 0.994 were reported in the study.
• Before initiating the study, 40 recurrent cancers were observed in patients with a history of malignancy (3 in the exposed and 37 in the unexposed setting with IR 0.92 and 0.82, respectively and adjusted HR of 0.828
• There were 218 patient years of exposure to immunosuppressants in the dupilumab-exposed group and 1393 in the unexposed group.

Concluding further, they wrote, "Based on the findings of our study, we report no association between dupilumab and the development of primary or recurrent malignancy.

Our study's results align with the current International Eczema Council recommendation, according to which dupilumab be used as first-line therapy for patients with a history of malignancy.

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.

Further reading:

Owji S, Ungar B, Dubin DP, Poplausky D, Young JN, Ghalili S, Han J, Srinivasan D, Packer S, Pavel AB, Correa da Rosa J, Guttman-Yassky E, Gulati N. No association between dupilumab use and short-term cancer development in atopic dermatitis patients. J Allergy Clin Immunol Pract. 2022 Dec 26:S2213-2198(22)01331-9. doi: 10.1016/j.jaip.2022.12.018.