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Background: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis.Methods: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060.Findings: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported.Interpretation: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis.Funding: Pfizer. [ABSTRACT FROM AUTHOR]

Limited treatment options are available for adolescents with moderate-to-severe atopic dermatitis (AD). Tralokinumab is a high-affinity, fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of inflammation in AD. In the phase III ECZTRA 6 trial (NCT03526861), tralokinumab 150 or 300 mg monotherapy every 2 weeks (Q2W) was effective and well tolerated in paediatric patients aged 12–17 years, and tralokinumab 300 mg was recently approved in Europe for the treatment of adolescents with moderate-to-severe AD. To report the efficacy and safety of tralokinumab 300 mg in adolescents with AD over the entire 52-week ECZTRA 6 study period. Patients were randomized to tralokinumab 300 mg Q2W (n=97) or placebo (n=94) for 16 weeks. At week 16, patients were initiated on tralokinumab and achieved the primary endpoints (Investigator’s Global Assessment [IGA] 0/1 and/or Eczema Area and Severity Index [EASI]-75), without the use of rescue treatment (topical/systemic AD therapy), were re-randomized to tralokinumab 300 mg Q2W/Q4W monotherapy for 36 additional weeks. During this blinded maintenance period, patients exhibiting a pre-defined relapse relative to their week 16 response were transferred to the open-label arm and treatment with tralokinumab 300 mg Q2W plus optional topical calcineurin inhibitors (TCIs) or topical corticosteroids (TCSs). Patients not achieving the primary endpoints were transferred to the open-label arm at week 16. A pre-specified treatment policy approach for the analyses was adopted using observed data, regardless of rescue medication and treatment discontinuation, to better reflect real-world treatment scenarios. Missing data were imputed using multiple imputations. Treatment differences for the binary endpoints were analysed using the Cochran-Mantel-Haenszel method stratified by region, and baseline IGA. Continuous endpoints were analysed using analysis of covariance accounting for the treatment, region, baseline IGA and baseline outcome value. Post-hoc analyses were conducted by pooling week 16–52 data for all patients initially randomized to tralokinumab 300 mg Q2W, irrespective of the response achieved at week 16, the dosing regimen received beyond week 16, or whether discontinuing treatment before week 16. At week 16, greater proportions of tralokinumab-treated patients (300 mg Q2W vs. placebo) achieved EASI-75 (38.4% vs. 23.5%; difference 15.4% [standard error, SE 6.53%]; P=0.0186) and EASI-90 (23.9% vs. 10.4%, difference 13.6% [SE 5.55%]; P=0.0142). Pooling all patients initially randomized to tralokinumab 300 mg Q2W and subsequently continuing on Q2W/Q4W monotherapy or Q2W plus optional TCI/TCS, response rates increased to 68.8% (EASI-75) and 42.8% (EASI-90) at week 52. Similarly, mean [SE] EASI and SCORing AD (SCORAD) improved with tralokinumab vs. placebo (EASI: 59.62% [4.36%] vs. 37.90% [5.16%]; P=0.0006 and SCORAD: 43.72% [3.13%] vs. 24.91% [3.31%]; P<0.0001) at week 16, with further improvement to 77.95% [2.96%] and 60.77% [2.81%] at week 52, respectively. Cumulative proportions of patients using concomitant TCI/TCS as rescue therapy during the first 16 weeks were lower with tralokinumab (29.9%) vs. placebo (54.3%). Over 52 weeks, the cumulative proportion of tralokinumab-treated patients using TCI/TCS increased to 47.4%, as TCI/TCS was permitted as optional concomitant medication in the open-label arm. Through week 16, proportions of patients with ≥1 adverse event (AE) were (tralokinumab 300 mg vs. placebo) 64.9 vs. 61.7%; ≥1 serious AE, 1.0 vs. 5.3%; AEs leading to discontinuation, 0% vs. 0%. The number of patients with conjunctivitis (incl. bacterial and allergic) was low (3.1% vs. 2.1%). The safety profile of tralokinumab 300 mg through week 52 was consistent with that at week 16. At week 16, tralokinumab 300 mg improved the extent and severity of AD compared with a placebo in adolescent patients with moderate-to-severe AD. Response rates progressively improved with continued tralokinumab plus optional TCS/TCI. Tralokinumab was well tolerated with a reassuring long-term safety profile over 52 weeks. [ABSTRACT FROM AUTHOR]