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Dupilumab-Associated Adverse Events During Treatment of Allergic Diseases

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Abstract

Among the new biological therapies for atopic diseases, dupilumab is a fully human monoclonal antibody directed against IL-4Rα, the common chain of interleukin-4 and interleukin-13 receptors. Dupilumab showed clinical improvements in patients with atopic dermatitis, asthma, and chronic rhinosinusitis and is currently under development for other indications. While dupilumab is considered to be well tolerated, a number of recent publications have reported various adverse events. This review aims to summarize the current knowledge about these adverse events, which may help clinicians to improve the follow-up of patients on dupilumab. Injection-site reactions are the most common reported adverse event. However, dupilumab has also been shown to cause ophthalmic complications (e.g., dry eyes, conjunctivitis, blepharitis, keratitis, and ocular pruritus), head and neck dermatitis, onset of psoriatic lesions, progression of cutaneous T-cell lymphoma exacerbation, alopecia areata, hypereosinophilia, and arthritis. Most are managed during dupilumab treatment continuation, but some (e.g., severe conjunctivitis) may result in a discontinuation of treatment. Their molecular origin is unclear and requires further investigations. Among other hypothesis, it has been suggested that T helper (Th)2-mediated pathway inhibition may worsen Th1/Th17-dependent immune responses. An ophthalmological examination for the presence of potential predictive indicators of ophthalmic adverse events is recommended before initiation of dupilumab therapy.

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Abbreviations

AA:

Alopecia areata

AD:

Atopic dermatitis

CRSwNP:

Chronic rhinosinusitis with nasal polyps

CTCL:

Cutaneous T cell lymphoma

Ig:

Immunoglobulin

IL:

Interleukin

IFN:

Interferon

Th:

T helper

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Acknowledgements

We thank the French Society for Allergology, the French Society for Dermatology and the Atopic Eczema Research Group (GREAT) of the French Society for Dermatology for their support.

Funding

Société Française de Dermatologie et de Pathologie Sexuellement Transmissible. Société Française d'Allergologie.

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Authors and Affiliations

  1. Infinity, Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), Toulouse University, CNRS, Paul Sabatier Toulouse III University, Inserm, Toulouse, France

    Anna Kychygina, Myriam Cassagne, Marie Tauber, Stéphane Galiacy, Carle Paul, Pierre Fournié & Michel Simon

  2. Department of Ophthalmology, Toulouse Hospital, Toulouse, France

    Myriam Cassagne, Stéphane Galiacy & Pierre Fournié

  3. Department of Dermatology, CHU and Toulouse III University, Toulouse, France

    Marie Tauber & Carle Paul

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  1. Anna Kychygina
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Correspondence to Michel Simon.

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AK, MC, PF, SG, and MS declare no conflicts of interest. MT is an investigator for AbbVie, Boehringer Engelheim, Eli Lilly, Galderma, LEO Pharma, Pierre Fabre, and Sanofi–Regeneron and a consultant or member of the advisory board for Sanofi–Regeneron. CP is an investigator or consultant for AbbVie, Astellas, Eli Lilly, LEO Pharma, Pierre Fabre, and Regeneron and Sanofi.

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Kychygina, A., Cassagne, M., Tauber, M. et al. Dupilumab-Associated Adverse Events During Treatment of Allergic Diseases. Clinic Rev Allerg Immunol 62, 519–533 (2022). https://doi.org/10.1007/s12016-022-08934-0

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