The Use of Morphology‐Directed Targeted Immunosuppression With Dupilumab in Cutaneous Immunotherapy Related Adverse Events

As the indications for cancer immunotherapy expand to include a broader patient base and less aggressive cancers, it is critical to conduct high‐quality studies that explore alternatives to glucocorticoids for managing immune‐related adverse events (irAEs). Among the various irAEs, cutaneous immune‐related adverse events (cirAEs) are most prevalent, affecting over 50% of patients undergoing immunotherapy.

The management of cirAEs typically involves the use of topical glucocorticoids for mild cases, while systemic glucocorticoids are reserved for moderate to severe cases [1]. However, systemic glucocorticoids—especially at doses exceeding 10 mg of prednisone equivalents daily—present both theoretical and practical disadvantages. They can broadly inhibit the effects of immunotherapy and have been associated with increased risks of cancer progression and all‐cause mortality related to high corticosteroid use [2].

While corticosteroids may effectively address various disease patterns, it is essential to differentiate between cirAE manifestations. Recognizing the distinct patterns linked to phenotype‐specific cytokines can offer long‐term corticosteroid‐sparing opportunities, thereby preserving patient quality of life and enabling the continuation of life‐saving immunotherapy. Dupilumab, an inhibitor of interleukin (IL)‐4 and IL‐13 receptors, warrants further investigation due to its potential to inhibit the Th2 pathway, which is upregulated in morphologies like eczema, lichen planus, pruritus without rash, and bullous pemphigoid [3].

In this issue, Koumprentziotis et al. perform a systematic review to characterize the use of dupilumab in managing cirAEs [4]. Through comprehensive search strategies, they identified 25 articles encompassing 136 patients. Among these, dupilumab demonstrated remarkable efficacy, showing clinical improvement in 91.8% of patients with eczema, 93% with bullous pemphigoid, 95.5% with morbilliform eruptions, and 100% with lichenoid dermatitis.

In addition to its impressive efficacy, the safety profile of dupilumab in this patient population mirrors that observed in the general dermatologic population receiving the drug. Within the systematic review, there was one case of new psoriasiform dermatitis, one case of an injection site reaction, and three cases of conjunctivitis. Although long‐term data on cancer outcomes for patients requiring dupilumab remain limited, existing safety data from the broader population are reassuring. A five‐year retrospective study involving 9707 patients with atopic dermatitis, of whom 1627 received dupilumab, found no increased risk of new primary cancers or cancer recurrence among those treated with dupilumab [5].

We commend Koumprentziotis et al. for enhancing the existing knowledge on morphology‐directed targeted immunosuppression. However, we believe that dermatologists are already aware of the safety and efficacy of dupilumab across these irAE morphologies. It is crucial for oncologists to recognize this data, for professional societies and oncology guideline committees to advocate for earlier use of dupilumab, and for insurers and third‐party payers to support access to this essential medication.

Conflicts of Interest

Dr. Brittany Dulmage has received research funding from the Dermatology Foundation and clinical trials for Onquality. Dr. Benjamin H. Kaffenberger has received research funding from Biogen, Merck, BMS, Onquality, InflaRx, The National Psoriasis Foundation, and Dermatology Foundation, and consulting fees from Biogen, Elsevier, Eli Lilly, Novartis, Novocure, and ADC therapeutics, and serves on the NCCN panel for immunotherapy toxicities.

Linked Articles

This article is linked to https://doi.org/10.1111/ijd.17850.

Data Availability Statement

The authors have nothing to report.