Interleukin‐13 inhibition and cancer risk: reply to Tang and Chen

We read with great interest the article by Tang and Chen, addressing the potential cancer risk associated with interleukin-13 (IL-13) inhibitors. 1 The IL-13-specific monoclonal antibodies tralokinumab and lebrikizumab, as well as the dual IL-4/IL-13 inhibitor dupilumab, are approved for the treatment of atopic dermatitis (AD). 2 Both clinical trials and an increasing number of real-world studies have demonstrated favorable efficacy and safety profiles for these agents. 3,4Moreover, a growing body of literature is focusing on their use in special populations and patients with comorbidities, including those with a history of malignancy. 5IL-13 inhibitors act by selectively targeting the Th2 immune response, which is primarily involved in allergic and anti-parasitic immunity, without significantly affecting the Th1 and cell-mediated pathways that are crucial for anti-tumor immune surveillance.Due to this mechanism of action, as well as their expanding role in clinical practice, current guidelines and expert consensus statements support the use of IL-13 inhibitors in patients with AD and a personal history of cancer or concurrent neoplastic disease, particularly when compared to conventional immunosuppressants (e.g., cyclosporine) or Janus kinase (JAK) inhibitors. [3][4]4][5] Despite their relatively recent approval, safety concerns have emerged.A study by Lavin et al., utilizing data from the FDA Adverse Event Reporting System (FAERS), identified dupilumab as having both the highest absolute number and the highest reporting odds ratio of cutaneous T-cell lymphoma (CTCL) reports among all biologics analyzed, including TNF- inhibitors, IL-12/23 inhibitors, This finding suggests a modest but statistically significant increased risk of CTCL in patients treated with dupilumab.Furthermore, FAERS data also include cases of CTCL associated with tralokinumab and lebrikizumab.Several hypotheses have