Safety of Tralokinumab in Adult Patients With Moderate-to-Severe Atopic Dermatitis: Pooled Analysis of Five Randomized, Double-blind, Placebo-controlled Phase 2 and Phase 3 Trials


Eric L. Simpson, Department of Dermatology, Oregon Health & Science University, Portland, OR, USA.
Joseph F. Merola, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Jonathan I. Silverberg, Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
Kristian Reich, Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Richard B. Warren, Dermatology Centre, Salford Royal NHS Foundation Trust, and NIHR Biomedical Research Centre, The University of Manchester, Manchester, UK.
Delphine Staumont-Sallé, Dermatology Service, Lille University Hospital, Inserm U1286 INFINITE (Institute for Translational Research in Inflammation), Lille University, Lille, France.
Giampiero Girolomoni, Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy.
Kim Papp, Probity Medical Research and K Papp Clinical Research, Waterloo, ON, Canada.
Marjolein de Bruin-Weller, National Expertise Center for Atopic Dermatitis, Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, the Netherlands.
Jacob P. Thyssen, Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Rebecca Zachariae, LEO Pharma A/S, Ballerup, Denmark.
Christiana K. Olsen, LEO Pharma A/S, Ballerup, Denmark.
Andreas Wollenberg, Klinikum der Universität München, Klinik und Poliklinik für Dermatologie und Allergologie, Munich, Germany.

Document Type

Journal Article

Publication Date



The British journal of dermatology




BACKGROUND: Tralokinumab is a fully human monoclonal antibody that neutralizes the activity of interleukin-13, a key pathogenic driver of atopic dermatitis (AD). Clinical trials including adults with moderate-to-severe AD, up to 52 weeks' duration, showed tralokinumab was efficacious and well tolerated. OBJECTIVE: To characterize the safety profile of tralokinumab for the treatment of moderate-to-severe AD. METHODS: Safety and laboratory measures were assessed in pooled analyses of Phase 2 and 3 placebo-controlled clinical trials of tralokinumab in moderate-to-severe AD. RESULTS: 2285 patients were randomized in the initial treatment periods up to 16 weeks (1605 tralokinumab; 680 placebo). Frequency of any adverse event (AE) was 65.7% and 67.2% with tralokinumab and placebo, respectively (rate of 639.5 and 678.3 events per 100 patient-years of exposure [ep100PYE]; rate ratio [RR] 1.0; 95% confidence interval [CI], 0.9-1.1). Serious AEs occurred in 2.1% and 2.8% with tralokinumab and placebo (7.4 and 11.9 ep100PYE; RR 0.7; 95% CI, 0.4-1.2). Most common AEs occurring at higher frequency and rate with tralokinumab vs placebo were viral upper respiratory tract infection (15.7% vs 12.2%; 65.1 vs 53.5 ep100PYE), upper respiratory tract infection (5.6% vs 4.8%; 20.8 vs 18.5 ep100PYE), conjunctivitis (5.4% vs 1.9%; 21.0 vs 6.9 ep100PYE), and injection site reaction (3.5% vs 0.3%; 22.9 vs 4.0 ep100PYE). Some events in safety areas of interest occurred at lower frequency and rate with tralokinumab vs placebo: skin infections requiring systemic treatment (2.6% vs 5.5%; 9.7 vs 22.8 ep100PYE); eczema herpeticum (0.3% vs 1.5%; 1.2 vs 5.2 ep100PYE); opportunistic infections (3.4% vs 4.9%; 13.0 vs 21.3 ep100PYE); and serious infections (0.4% vs 1.1%; 1.3 vs 3.7 ep100PYE). AEs did not increase with continued maintenance and open-label treatment, including rates of common/serious AEs and AEs leading to study drug discontinuation. No clinically meaningful changes in mean laboratory measures were observed with treatment up to 1 year. CONCLUSIONS: Across the AD population pool from five clinical trials, tralokinumab was well tolerated, with consistent safety findings during treatment of moderate-to-severe AD patients. The safety profile during prolonged tralokinumab treatment was consistent with the initial treatment period; frequency of events did not increase over time.