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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., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Objectives: To describe new-onset IBD (new IBD) in patients treated with IL-17 inhibitors (IL-17i), to assess their incidence and to identify their risk factors in real life., Methods: A French national registry (MISSIL) aimed to report all cases of new IBD in patients treated with IL-17i from January 2016 to December 2019. Using the estimated number of patients treated by IL-17 in France during the study period, the annual incidence rates of new IBD was reported in IL-17i-treated patients. A case-control study was performed with two controls per new IBD case matched by gender, age and underlying inflammatory disease., Results: Thirty-one cases of new IBD under IL-17i were collected: 27 patients treated for spondyloarthritis and four patients for psoriasis. All were observed with secukinumab (SEK). The median time to onset of new IBD symptoms was 4.0 (1.5-7.5) months. SEK was discontinued in all patients. The evolution was favourable with complete resolution (17/31), improvement (7/31) or stabilization (5/31). Two patients died: one due to a massive myocardial infarction and one due to post-colectomy complications. The incidence of new IBD decreased from 0.69/100 patient-years [PY] (7/1010) in 2016 to 0.08/100 PY (6/7951) in 2019. No previous treatment with etanercept (odds ratio [OR] = 0.33, 95% CI: 0.14-0.80, P = 0.014) and low number of previous biologic therapies (OR = 0.67, 95% CI: 0.47, 0.94, P = 0.021) were significantly associated with new IBD., Conclusion: The incidence of new IBD was low and decreased from 2016 to 2019. The outcome was favourable in 24 out of 31 patients, but two patients died., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Infliximab (IFX) is effective in inducing and maintaining remission in patients with luminal and anoperineal Crohn's disease (CD). However, treatment failure within 12 months after initiating IFX is observed in a significant proportion of patients. The aim of the present study was to determine whether the body mass index (BMI) affects response to IFX during the first year of treatment in patients with CD., Methods: All patients with luminal CD who began IFX between January 2010 and May 2014 were prospectively included. BMI was calculated before IFX treatment was begun, and patients were divided into 3 groups: normal BMI (BMI < 25 kg/m), overweight patients (BMI of 25.0-30 kg/m), and obese patients (BMI > 30.0 kg/m). The primary outcome was to evaluate the rate and delay of IFX optimization during the first year of treatment among normal weight, overweight, and obese patients., Results: One hundred forty patients were included. Demographic and clinical characteristics at IFX initiation were comparable among the 3 groups. Within 12 months after the initiation of IFX, the rate of IFX optimization was significantly higher in overweight and obese patients than in the normal BMI group: 52%, 56%, and 20%, respectively (P = 0.0002). The median time until optimization of IFX was significantly shorter in overweight and obese patients than in the normal BMI group: 7, 7, and 10 months, respectively (P = 0.03). A BMI >25 kg/m was significantly associated with IFX optimization within 12 months on multivariate analysis., Conclusion: This is the first study to show that optimization of IFX is more frequent and faster in obese and overweight patients with CD and occurs within 12 months after beginning IFX, suggesting that an induction regimen with higher doses of IFX and a tight control of IFX concentrations may be needed in these patients.

Levamisole (an increasingly frequent contaminant of cocaine) can cause antineutrophil cytoplasmic antibody-associated vasculitis. Dermatologists should consider a diagnosis of cocaine/levamisole-associated cutaneous vasculopathy syndrome in cases of purpura of the ears and/or extensive retiform purpura in drug users. We report a case of particularly severe levamisole-induced necrotic purpura and immunological abnormalities in a 40-year-old woman., (© 2017 British Association of Dermatologists.)

Acute generalized exanthematous pustulosis (AGEP) is a severe adverse cutaneous reaction, which is mostly due to drugs, but which has also been described as occurring after infections. We report a case of severe AGEP with extensive blistering mimicking toxic epidermal necrolysis (TEN) in a 47-year-old woman. This was associated with a life-threatening primary mumps infection, complicated by perimyocarditis and encephalitis. The recent increase in the incidence of mumps should lead physicians to be aware of the uncommon clinical features and complications of this disease., (© 2014 British Association of Dermatologists.)