No association between dupilumab use and short-term cancer development in atopic dermatitis patients

Owji, Shayan; Ungar, Benjamin; Dubin, Danielle P; Poplausky, Dina; Young, Jade N; Ghalili, Sabrina; Han, Joseph; Srinivasan, Dhipthika; Packer, Sarah; Pavel, Ana B.; Rosa, Joel Corrêa da; Guttman‐Yassky, Emma; Gulati, Nicholas

doi:10.1016/j.jaip.2022.12.018

Cited by 12 publications

(11 citation statements)

References 9 publications

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“…One of the more studied examples of this phenomenon is the biologic drug dupilumab, an IL-4 receptor inhibitor. Dupilumab has been approved for atopic diseases like asthma, AD, chronic rhinosinusitis, and eosinophilic esophagitis, 100 and as discussed earlier has been observed to increase immunosuppressive B cells in severe asthma. 45 While the role of IL-4 on cancer development is still actively under investigation, there is some preclinical data suggesting that IL-4 receptor blockade may lead to a loss of protection against certain malignancies.…”

Section: Connection Between Allergy Immunotherapy and Cancer Riskmentioning

confidence: 93%

“…One of the more studied examples of this phenomenon is the biologic drug dupilumab, an IL‐4 receptor inhibitor. Dupilumab has been approved for atopic diseases like asthma, AD, chronic rhinosinusitis, and eosinophilic esophagitis, 100 and as discussed earlier has been observed to increase immunosuppressive B cells in severe asthma 45 …”

Section: Developing Breg‐targeted Immunotherapiesmentioning

confidence: 95%

“…Owji et al examined patients with AD using dupilumab for at least 2 months over a period of 5 years and did not find an association with the development of primary or recurrent malignancy. 100 However, there still have been case reports of patients on dupilumab who subsequently developed cancers while on treatment. 102 Whether other risk factors or dupilumab played a larger role in these outcomes is questionable; however, at this point, it would be prudent to suggest that patients with active cancer should likely refrain from undergoing these immunomodulatory therapies.…”

Section: Connection Between Allergy Immunotherapy and Cancer Riskmentioning

confidence: 99%

“…The clinical data is similarly difficult to parse through with somewhat conflicting results. Owji et al examined patients with AD using dupilumab for at least 2 months over a period of 5 years and did not find an association with the development of primary or recurrent malignancy 100 . However, there still have been case reports of patients on dupilumab who subsequently developed cancers while on treatment 102 .…”

Section: Developing Breg‐targeted Immunotherapiesmentioning

confidence: 99%

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The dichotomy of regulatory B cells in cancer versus allergic disease

Dang,

Yu,

Galant‐Swafford

et al. 2023

Molecular Carcinogenesis

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Regulatory B cells (Bregs) are an immunosuppressive cell phenotype that affects the immune system by limiting the inflammatory cascade. Dysregulation of Bregs can interestingly play a dichotomous role in the pathophysiology of many diseases and is especially highlighted when examining cancer pathology compared to allergic disease. This study reviews the existing literature on Bregs and compares their role in allergic disease in contrast to cancer development. Upregulation of Bregs in cancer states has been associated with poor prognostic outcomes across various cancer types, and Breg proliferation was associated with chronic interferon signaling, activation of the BCR–BTK (B cell receptor‐Bruton's tyrosine kinase) pathway, and release of C–X–C motif ligand 13. In contrast, Breg dysfunction has been identified as a key mechanism in many allergic diseases, such as allergic asthma, allergic rhinitis, atopic dermatitis, and contact dermatitis. Development of Breg‐targeted immunotherapies is currently at the preclinical level, but strategies differentially focus on Breg depletion in cancer versus Breg stimulation in allergy. Our review highlights the divergent functions that Bregs play in cancer compared to allergy. We conclude that natural homeostasis hinges on a fine balance between the dichotomous role of Bregs—over or underactivation can result in a pathological state.

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Section: Connection Between Allergy Immunotherapy and Cancer Riskmentioning

confidence: 93%

Section: Developing Breg‐targeted Immunotherapiesmentioning

confidence: 95%

Section: Connection Between Allergy Immunotherapy and Cancer Riskmentioning

confidence: 99%

Section: Developing Breg‐targeted Immunotherapiesmentioning

confidence: 99%

See 2 more Smart Citations

The dichotomy of regulatory B cells in cancer versus allergic disease

Dang,

Yu,

Galant‐Swafford

et al. 2023

Molecular Carcinogenesis

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“…A few tumor events have been reported in real-world study, while a retrospective study implied that no association between dupilumab and malignancies existed during a 5-year follow-up period. 6 We believe that it is necessary to report tumor events we observed in our center as a supplement to our knowledge (Table 1).…”

Section: Adverse Events No (%) Eventsmentioning

confidence: 99%

Efficacy and safety analysis of Dupilumab for atopic dermatitis of all ages in Chinese population: Real‐world data from a single center

Yang,

Wen,

Shi

et al. 2024

Allergy

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Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review

Mansilla-Polo,

Morgado-Carrasco

2024

Dermatol Ther (Heidelb)

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Introduction Biological drugs (BD) and Janus kinase inhibitors (JAKi) have revolutionized the treatment of diverse dermatoses. However, there are concerns regarding their safety, especially the risk of cancer and opportunistic infections. Here, we discuss the risk of cancer associated with the BD and JAKi used in dermatology. Methods A narrative review was carried out. All relevant articles evaluating the risk of cancer associated with BD or JAKi and published between January 2010 and February 2024 were selected. Results Multiple large studies have evaluated the association between BD, JAKi and cancer risk. However, there is a lack of prospective, comparative studies. Overall, patients undergoing BD and JAKi present a cutaneous cancer incidence similar to that in the general population. The drugs more strongly associated with non-skin cancer risk were anti-tumor necrosis factor (anti-TNFs) agents and JAKi (especially tofacitinib and oral ruxolitinib). This risk appears to increase with age, the presence of other factors (such as chronic immunosuppression from previous drugs or other comorbidities), and specific diseases such as rheumatoid arthritis (RA) and myelodysplastic syndrome. Conversely, BD such as interleukin (IL)-17 and IL-23 inhibitors may even reduce the risk of some visceral and hematological malignancies. In patients with dermatological conditions such as psoriasis and atopic dermatitis, the risk of malignancies may be lower than in other subgroups, and probably comparable to the general population. Conclusions The incidence of cancer in patients undergoing BD or JAKi is generally low. This incidence can be higher in elderly patients with RA or myelodysplastic syndrome, and in those undergoing prolonged therapy with tofacitinib or ruxolitinib (oral), or anti-TNF agents.

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No association between dupilumab use and short-term cancer development in atopic dermatitis patients

Cited by 12 publications

References 9 publications

The dichotomy of regulatory B cells in cancer versus allergic disease

The dichotomy of regulatory B cells in cancer versus allergic disease

Efficacy and safety analysis of Dupilumab for atopic dermatitis of all ages in Chinese population: Real‐world data from a single center

Biologics Versus JAK Inhibitors. Part I: Cancer Risk. A Narrative Review

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