Introduction (contexte de la recherche) Patients (pts) with moderate-to-severe atopic dermatitis (AD) often have an inadequate response to topical therapies. Long-term use of systemic immunosuppressants is not recommended due to safety concerns. To report the dupilumab safety profile in pts with moderate-to-severe AD from an open-label extension (OLE) study ( NCT01949311 ) to 204 weeks (wks). Adults with moderate-to-severe AD from any dupilumab parent study (phase 1–3) were enrolled into the long-term, multicenter OLE study (duration up to 5 years in certain countries). In the OLE, pts were treated with 300 mg dupilumab weekly (qw). In 2019, pts transitioned to the approved 300 mg every 2 weeks (q2w) dose. Concomitant treatments for AD were permitted. LIBERTY AD CHRONOS ( NCT02260986 ) 52-wk safety results for adults with moderate-to-severe AD receiving dupilumab 300 mg qw plus TCS were provided as a comparison. Data shown are for the overall study population ( n = 2677). In all, 2207 pts completed treatment up to Wk 52, 1,065 up to Wk 100, 557 up to Wk 148, 362 up to Wk 172 and 352 up to Wk 204. 240 pts had treatment duration > 204 wks. Most withdrawals during the OLE study period were due to dupilumab approval and commercialization in the country in which the patient had enrolled (810 [59.5%]); 114 (8.4%) patients withdrew due to adverse events (AEs) and 58 (4.3%) withdrew due to lack of efficacy. Exposure-adjusted incidence rates of treatment-emergent AEs (TEAEs) were lower in this OLE vs. the 300 mg qw + TCS arm of the 1-year CHRONOS trial (167.5 vs. 322.4 number of patients/100 patient–years). In this OLE, 9.8%, ≥ 1 severe TEAEs; 1.2%, ≥ 1 serious TEAE related to study drug; with 3.7% ≥ 1 TEAEs resulting in permanent drug discontinuation. The most common TEAEs were nasopharyngitis (28.9%) and conjunctivitis (20.0%, including conjunctivitis, conjunctivitis allergic/bacterial/viral, and atopic keratoconjunctivitis). Among pts with conjunctivitis TEAEs, 95% were mild/moderate; 87% of conjunctivitis events were recovered/resolved. The OLE long-term study data in adults with moderate-to-severe AD extends the previously reported safety profile of dupilumab to 4 years.