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, of up to 52 weeks’ duration, showed tralokinumab was efficacious and well tolerated. Objectives: 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 II and III placebo-controlled clinical trials of tralokinumab in moderate-to-severe AD (NCT02347176, NCT03562377, NCT03131648, NCT03160885, NCT03363854). Results: In total, 2285 patients were randomized in the initial treatment periods up to 16 weeks (1605 tralokinumab, 680 placebo). The frequencies of any adverse event (AE) were 65·7% for tralokinumab and 67·2% for placebo. The respective rates were 640 and 678 events per 100 patient-years of exposure (ep100PYE); rate ratio 1·0, 95% confidence interval (CI) 0·9–1·1. Serious AEs occurred in 2·1% of patients with tralokinumab and 2·8% with placebo (7·4 and 11·9 ep100PYE; rate ratio 0·7, 95% CI 0·4–1·2). The most common AEs occurring at a 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 a 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 or 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 patients with moderate-to-severe AD. The safety profile during prolonged tralokinumab treatment was consistent with that during the initial treatment period; the frequency of events did not increase over time. What is already known about this topic? Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key cytokine driving skin inflammation and epidermal barrier dysfunction in atopic dermatitis (AD). In clinical trials in moderate-to-severe AD, tralokinumab provided significant and early improvements in the extent and severity of AD and was well tolerated, with an overall safety profile comparable with placebo over 52 weeks. What does this study add? We report the frequency and rate of adverse events (AEs) from pooled observations of over 2000 patients from five phase II and phase III placebo-controlled clinical trials of tralokinumab in moderate-to-severe AD. During initial treatment up to 16 weeks, the frequencies of any AE and of serious AEs were similar for tralokinumab and placebo. AE rates did not increase with continued treatment up to 52 weeks. Common AEs occurring more frequently with tralokinumab vs. placebo were viral and upper respiratory tract infection, conjunctivitis and injection-site reaction. Some events occurred at a lower frequency and rate with tralokinumab vs. placebo, such as skin infections requiring systemic treatment, eczema herpeticum and opportunistic and serious infections. No clinically meaningful changes in mean laboratory measures were observed.
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