Dupilumab for Eczema Linked to Risk Increase for Cutaneous T-Cell Lymphoma

Credit: Pexels

The treatment of atopic dermatitis with dupilumab is associated with a relative risk increase of developing cutaneous t-cell lymphoma, according to new findings, and such risk is highest within the initial year of treatment and among adults.¹

These data resulted from a new analysis conducted to explore the risk of developing this condition following treatment with dupilumab for eczema, also known as atopic dermatitis.

This new study was led by Jenna Mandel, an MD candidate at the Thomas Jefferson University’s department of dermatology and cutaneous biology in Philadelphia. Mandel et al. highlighted prior research on cutaneous t-cell lymphoma following dupilumab therapy, adding that a wide array of literature has described the connection between TNF-alpha inhibitors and the development of this condition.²

“However, despite these concerning findings, population-level analyses evaluating the risk of (cutaneous t-cell lymphoma) following dupilumab use for (eczema) are lacking,” Mandel and colleagues wrote. “In this study, we utilized a large population database to identify and examine all cases of cutaneous T-cell lymphoma…following dupilumab use in (eczema) patients within the United States.”¹

Background and Design

The research team conducted their study with a retrospective cohort design, looking at data drawn from a deidentified global health record database known as TriNetX. The database is made up of over 107 million patients from 62 healthcare organizations within the US collaborative network.

To guide the study design, a thorough review of all documented cases of cutaneous T-cell lymphoma (CTCL) following the use of dupilumab was conducted. The study compared those with diagnoses of atopic dermatitis who had been given dupilumab to individuals who had not been treated with this medication.

There were 1,092,798 subjects who the investigators identified that had been diagnosed with eczema and were not treated with dupilumab or other selected biologics. A total of 19,612 were found to have been diagnosed with eczema and treated with the drug but had not been given any other selected biologic therapies.

The research team matched the participants using 1:1 propensity score matching. They considered elements such as race, age at the time of eczema diagnosis, and biological sex, leading to their formulation of 2 sets of 19,612 subjects each.

The risk of developing cutaneous t-cell lymphoma was evaluated by assessing outcomes related to Sézary syndrome, Mycosis Fungoides, and unspecified cutaneous t-cell lymphoma from the beginning of treatment to the study’s end. The team carried out a subgroup analysis to categorize individuals into 3 age groups based on national rates of cutaneous t-cell lymphoma incidence: ≤40, 40–60, and ≥60 years.

The team also carried out another subgroup analysis, during which they stratified those included in the dupilumab cohort based upon their treatment’s duration.

Findings

The investigators noted that their study’s participants had an average age of 32.3 years, adding that about 52% of these individuals had been female and that no major differences were identified between the 2 cohorts they compared.

Those treated with dupilumab were shown to have a significantly higher relative risk cutaneous T-cell lymphoma development versus individuals who had never been treated with dupilumab (RR = 4.59, 95% confidence interval 2.459–8.567, P < .0001).

Additionally, the team reported that 54.5% of those with cutaneous t-cell lymphoma who had been given dupilumab were reported to be over 60 years of age. Despite this, 100% of those in the untreated cohort who had cutaneous t-cell lymphoma were individuals over 60.

The majority of subjects with cutaneous t-cell lymphoma following dupilumab administration (62%) had been diagnosed within the initial year of the drug’s use. The research team also pointed out their study’s limitations.

“Instances where the recorded number of patients with a specific condition is 10 or fewer, TriNetX reports the incidence as 10, regardless of the actual incidence,” they noted. “Relative risks are calculated in TriNetX with the assumption that the value reported as ≤10 is 10, regardless of the true number. Our analysis using TriNetX was limited due to its retrospective nature.”

References

1. ^{Mandel, Jenna, Mehta, Jaanvi, Hafer, Ramsay, Ayub, Mahaa, Nusrat, Faria, Yang, Henry, Porcu, Pierluigi, Nikbakht, Neda, Increased Risk of Cutaneous T-Cell Lymphoma Development after Dupilumab Use for Atopic Dermatitis, Dermatologic Therapy, 2024, 9924306, 8 pages, 2024. https://doi.org/10.1155/2024/9924306.}
2. ^{Martinez-Escala ME, Posligua AL, Guitart J, et al. Progression of undiagnosed cutaneous lymphoma after anti-tumor necrosis factor-alpha therapy. Journal of the American Academy of Dermatology. (2018) 78, no. 6, 1068–1076, https://doi.org/10.1016/j.jaad.2017.12.068, 2-s2.0-85044536956.}