Long-Term Dupilumab Treatment Is Not Associated with an Increased Overall Risk of Infections in Adults with Moderate-to-Severe Atopic Dermatitis: Results from an Open-Label 5-Year Extension Study

Patients with atopic dermatitis (AD) are at an increased risk for infections. Here, we report a confirmatory follow-up study analyzing the incidence of infections in adults with moderate-to-severe AD treated with dupilumab for up to 5 years. Infections in adults with moderate-to-severe AD treated with dupilumab 300 mg weekly (qw) or every 2 weeks (q2w; approved regimen) were assessed for up to 5 years in the open-label extension study, LIBERTY AD OLE. Topical corticosteroids (TCS) and calcineurin inhibitors (TCI) were permitted. Exposure-adjusted incidence rates [number of patients with at least one event per 100 patient-years (nP/100 PY)] are reported. Since the OLE had no control arm, safety results from the placebo + TCS arm of the 1-year LIBERTY AD CHRONOS study are included for comparisons. Of the 2677 patients included, 2207 (82.4%) completed up to week 52, 557 (20.8%) up to week 148, and 334 (12.5%) up to week 260; 226 patients (8.4%) switched from qw to q2w during the trial due to a protocol amendment. Overall infections (70.69 nP/100 PY), serious infections (0.87 nP/100 PY), severe infections (0.92 nP/100 PY), and infections leading to treatment discontinuation (0.34 nP/100 PY) were consistent with previous 4-year open-label extension (OLE) analyses and were low compared with 1-year results from the CHRONOS placebo + TCS arm. The cumulative number of patients with treatment-emergent serious or severe infections, non-herpetic or herpetic infections, and total skin infections decreased throughout the OLE study period. Limitations of this study include the absence of a placebo arm in the OLE, decreasing sample size at later time points, inclusion of qw dosing analyses (different from approved q2w dosing), and possible confounding effects of TCS/TCI use that may impact infection rates. Long-term dupilumab treatment for up to 5 years in adults with moderate-to-severe AD is not associated with an increased overall risk of infections. Graphical abstract available for this article. ClinicalTrials.gov Identifier: NCT01949311, NCT02260986. Atopic dermatitis, also known as eczema, is a chronic disease that causes dry skin, skin inflammation, and itching, which leads to scratching and further skin damage. Patients with atopic dermatitis have an increased risk of developing infections, including skin infections due to the damaged skin surface. This study investigated the rate of infection in adults with moderate-to-severe atopic dermatitis after 5 years of dupilumab treatment, at a dose of 300 mg of dupilumab every week or every 2 weeks. Patients were allowed to use topical corticosteroids or topical calcineurin inhibitors as needed. Over the 5-year study, the cumulative rate of infections decreased and was lower than that previously reported in atopic dermatitis patients treated with placebo and topical corticosteroids for 1 year. The rate of total infections, serious and severe infections, and infections leading to treatment discontinuation were similar to that reported in a previously published 4-year evaluation of this study. Notably, the cumulative number of patients with total skin infections decreased over 5 years of dupilumab treatment. In addition, the number of patients with severe infections appearing after the start of treatment, herpes viral infections, and infections not involving herpes virus also decreased yearly. The safety data presented here show that long-term dupilumab treatment does not increase the overall risk of infections and demonstrates that, with long-term treatment with dupilumab, adults with moderate-to-severe atopic dermatitis experience less infections over time.