Long-term Safety of Dupilumab in Adult Patients with Moderate to Severe Atopic Dermatitis

Introduction

Dupilumab is a recombinant human monoclonal antibody of the IgG4 class that inhibits the interleukin-4 and interleukin-13 signaling pathways. It is indicated for the treatment of moderate to severe AD in adults, adolescents, and children aged 6 years and older. It is also suitable for treating other type 2 inflammatory diseases, such as asthma bronchiale and chronic rhinosinusitis with nasal polyposis, when certain criteria are met.

Study Population

The safety of the therapy was evaluated in a cohort of 2677 patients with moderate to severe AD. Patients could be enrolled in the multicenter phase III OLE study if they had previously participated in clinical trials with dupilumab and had not discontinued treatment due to adverse effects (AEs).

Participants received subcutaneous dupilumab at a dose of 300 mg once weekly and later once every two weeks. Concurrent use of topical corticosteroids was reported by 53.3% of patients, 16.3% used topical calcineurin inhibitors, and a total of 13.6% used both medications. The safety profile of dupilumab was compared with data from the LIBERTY AD CHRONOS study, where patients used topical corticosteroids concurrently for 52 weeks.

At the time of analysis, a total of 1114 (41.6%) patients completed the OLE, 201 (7.5%) were still participating in the OLE, and the participation of the remaining patients had been terminated prematurely. A total of 202 (7.5%) patients participated in the OLE for at least 244 weeks (>4.5 years). Due to adverse effects, 114 (4.3%) subjects discontinued participation.

Results

A total of 14,569 AEs were reported in 2273 (84.9%) patients. The majority were mild or moderate, with severe events occurring in 9.8% of participants, and only 1.2% were directly related to dupilumab. Serious AEs were observed in 10.4% of individuals. Relatively common adverse events included nasopharyngitis (28.9%), worsening of atopic dermatitis (16.6%), upper respiratory tract infections (13.5%), herpes labialis (7.4%), conjunctivitis (10.3%), injection site reactions (5.2%), and headache (8.1%). The incidence of conjunctivitis, injection site reactions, and skin infections decreased over time. Overall results and the safety profile of dupilumab were comparable to data from the CHRONOS study.

Conclusion

The presented study supports the safety of long-term use of dupilumab in patients with moderate to severe atopic dermatitis. Adverse effects are mostly mild or moderate and do not lead to the discontinuation of treatment.

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Source: Beck L. A., Deleuran M., Bissonnette R. et al. Dupilumab provides acceptable safety and sustained efficacy for up to 4 years in an open-label study of adults with moderate-to-severe atopic dermatitis. Am J Clin Dermatol 2022; 23 (3): 393–408, doi: 10.1007/s40257-022-00685-0.