Open Access

Kristian Reich, Richard G. Langley, Juan Francisco Silvestre Salvador, Delphine Staumont-Sallé, Antonio Costanzo, Andrew E. Pink, Amy S. Paller, Norito Katoh, Andreas Wollenberg, Richard B. Warren, Andrew Blauvelt, Christian Bjerregård Øland, Ann-Marie Tindberg, Le Gjerum, Eric L. Simpson

• Background: Patients with moderate-to-severe atopic dermatitis (AD) require long-term management, and understanding the long-term safety of new treatments is a top priority for patients and healthcare professionals. Objectives: To evaluate the safety of tralokinumab in adults and adolescents with moderate-to-severe AD by conducting an integrated safety analysis of 7 placebo-controlled trials and the ongoing, open-label extension study ECZTEND. Methods: An initial 16-week placebo-controlled (PBO-CTRL) safety set and an all-tralokinumab (ALL-TRALO) safety set combining the placebo-controlled trials and ECZTEND (data cut-off 30 April, 2022) were analyzed. All treatment-emergent adverse events (AEs) were recorded. AEs of special interest (AESIs) were pre-defined. Safety areas of clinical interest for advanced systemic AD treatments were captured retrospectively. Proportions of patients with events and incidence rates (IR) per 100 patient-years of exposure (PYE) were calculated. PYE wasBackground: Patients with moderate-to-severe atopic dermatitis (AD) require long-term management, and understanding the long-term safety of new treatments is a top priority for patients and healthcare professionals. Objectives: To evaluate the safety of tralokinumab in adults and adolescents with moderate-to-severe AD by conducting an integrated safety analysis of 7 placebo-controlled trials and the ongoing, open-label extension study ECZTEND. Methods: An initial 16-week placebo-controlled (PBO-CTRL) safety set and an all-tralokinumab (ALL-TRALO) safety set combining the placebo-controlled trials and ECZTEND (data cut-off 30 April, 2022) were analyzed. All treatment-emergent adverse events (AEs) were recorded. AEs of special interest (AESIs) were pre-defined. Safety areas of clinical interest for advanced systemic AD treatments were captured retrospectively. Proportions of patients with events and incidence rates (IR) per 100 patient-years of exposure (PYE) were calculated. PYE was defined as the time until the first event or exposure end, whichever came first, and incidence was defined as the first event. Results: Safety results were similar between the PBO-CTRL safety set and ALL-TRALO safety set. In the latter, 2693 patients received tralokinumab for up to 238.5 weeks (≈4.5 years, PYE=5320.2). Most AEs were nonserious, mild or moderate in severity, and occurred with similar frequencies between tralokinumab and placebo in the PBO-CTRL safety set. The most common AEs that occurred at higher rates for tralokinumab vs. placebo were nasopharyngitis (IR ratio [IRR] comparing tralokinumab vs. placebo=1.26), conjunctivitis (IRR=3.11), and injection site reaction (IRR=19.57). Dermatitis atopic and asthma occurred at lower rates with tralokinumab vs. placebo (IRR=0.51 and 0.57, respectively). AESI eye disorders occurred at higher rates with tralokinumab vs. placebo (IRR=2.43), and 98% were mild to moderate. AESIs that were less frequent with tralokinumab vs. placebo included skin infections requiring systemic treatment (IRR=0.43) and eczema herpeticum (IRR=0.32). Rates of AEs of clinical interest (related to other approved systemic AD treatments) were low and similar between treatment groups. IRs of AEs did not increase with longer exposure in the ALL-TRALO safety set. Conclusions: Long-term use of tralokinumab in adults and adolescents with moderate-to-severe AD was well-tolerated and consistent with the initial placebo-controlled treatment period, with no new safety signals identified. Clinical trial registration: ECZTRA 1 (NCT03131648), ECZTRA 2 (NCT03160885), ECZTRA 3 (NCT03363854), ECZTRA 5 (NCT03562377), ECZTRA 6 (NCT03526861), ECZTRA 7 (NCT03761537), ECZTRA 8 (NCT04587453), and ECZTEND (NCT03587805; data cut-off 30 April, 2022).…