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

Br J Dermatol. 2022 Sep 9. doi: 10.1111/bjd.21867. Online ahead of print.


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.