Photo Credit: Md Babul Hosen
The following is a summary of “Integrative epidemiology and immuno-transcriptomics uncover a risk and potential mechanism for cutaneous lymphoma unmasking or progression with dupilumab therapy,” published in the November 2024 issue of Allergy and Immunology by Cabrera-Perez et al.
Dupilumab has been reported to be associated with the onset and progression of cutaneous T-cell lymphoma (CTCL).
Researchers conducted a retrospective study to analyze safety signals associated with dupilumab, focusing on CTCL, and to evaluate potential underlying mechanisms.
They analyzed the FDA pharmacovigilance database, FAERS, to evaluate dupilumab’s link to CTCL, comparing it with positive controls (conjunctivitis, eosinophilia, and arthralgia) and exposure controls (other medications, including JAK-inhibitors and tralokinumab) to reduce bias. They also used RNA sequencing datasets to explore potential mechanisms.
The results showed that between January 2019 and Q2 2023, FAERS reported 181,575 unique dupilumab-related adverse events (AEs), with 606 related to neoplasms. Dupilumab had a 30.0 times higher proportional reporting ratio (PRR) (95% CI: 25.0 – 35.9) for CTCL compared to other medications, with the highest risk in males aged 45-65. The PRRs for conjunctivitis, eosinophilia, and arthralgia were 35.6 (34.4 – 36.8), 2.15 (2.00 – 2.31), and 2.14 (2.07 – 2.18), respectively. The AE score identified conjunctivitis (AEscore 8.3) and CTCL (AEscore Single-cell transcriptomic studies showed similar changes in both conditions, with keratinocytes exhibiting the most significant divergence in IL4R and IL13RA1 expression, which was also noted in bulk RNA data.
The study concluded that dupilumab may unmask or progress CTCL through IL13 receptor blockade, like its effect in atopic dermatitis. However, further evaluation is needed due to the limitations of the FAERS database and the non-experimental design.
Source: jacionline.org/article/S0091-6749(24)01172-2/fulltext
