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Summary: Background: Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs and symptoms of moderate‐to‐severe atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of baricitinib with background topical corticosteroids (TCS) in patients with moderate‐to‐severe AD and inadequate response, intolerance or contraindication to ciclosporin A (CA). Methods: In this double‐blind, randomized, placebo‐controlled, phase III study, patients were randomized 1: 1: 2: 1 to placebo (N = 93), baricitinib 1 mg (N = 93), 2 mg (N = 185) or 4 mg (N = 92) with background TCS. The primary endpoint was the proportion of patients receiving baricitinib 4 mg or 2 mg (+ TCS) vs. placebo + TCS who achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index (EASI 75) at week 16. Results: Baricitinib 4 mg + TCS was superior to placebo + TCS for EASI 75 (4 mg: 32%, placebo: 17%, P = 0·031) at week 16 and for improvements in itch, skin pain and number of night‐time awakenings owing to itch. Improvements were maintained through 52 weeks of treatment. Treatment‐emergent adverse events (TEAEs) were more common with baricitinib than placebo (+ TCS); most were mild or moderate. The most frequent TEAEs with baricitinib 4 mg + TCS were nasopharyngitis, herpes simplex, influenza and headache. No deaths or deep vein thromboses were reported. Conclusions: Baricitinib 4 mg + TCS improved the signs and symptoms of moderate‐to‐severe AD through 52 weeks of treatment in patients with inadequate response, intolerance or contraindication to CA. The safety profile was consistent with previous studies of baricitinib in moderate‐to‐severe AD. What is already known about this topic?Ciclosporin A is indicated for the treatment of atopic dermatitis that is refractory to topical therapies. However, its use is limited by safety concerns and it may not provide adequate response for some patients.Baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor, has been shown to improve the signs and symptoms of moderate‐to‐severe atopic dermatitis as a monotherapy or in combination with topical corticosteroids. What does this study add?Baricitinib combined with background low‐ or moderate‐potency topical corticosteroids provided improvements in the signs and symptoms of moderate‐to‐severe atopic dermatitis through 1 year of treatment in patients with a contraindication, intolerance or failure to respond to ciclosporin A.The most common treatment‐emergent adverse events with baricitinib 4 mg were nasopharyngitis, herpes simplex, influenza and headache.The safety profile was consistent with previous studies in patients with moderate‐to‐severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Introduction Lebrikizumab (LEB) is a monoclonal antibody (Ab) that has shown efficacy and safety in patients with moderate-tosevere atopic dermatitis (AD) in Phase 2/3 trials. LEB targets IL-13 and inhibits signaling of the IL-4Ra/IL-13Ra1 complex. The potential immunomodulator effect of LEB necessitates investigating its impact on immune responses. Objectives: To report the seroresponses to the Tdap (Diphtheria/Tetanus Toxoids/Pertussis) and MCV (Meningococcal (Groups A, C, Y, and W-135)) vaccines in LEB-treated and placebo (PBO)-treated adult patients (aged 18-15 years) with moderate-to-severe AD; and to compare the efficacy of LEB vs PBO in the treatment of AD. Methods: ADopt-VA was a US Phase 3, 16-week (W) randomized, double-blind, placebo-controlled study to assess LEB impact on vaccine immune responses in adult patients with moderate-to-severe AD. The primary endpoint was the immune response to 2 vaccines, the Tdap and MCV. LEB was given as a 500 mg loading dose at baseline and W2, followed by 250 mg LEB Q2W. At W12, both vaccines (Tdap and MCV) were administered to all patients, LEB group N=107, Placebo (PBO) group N=81. Immune responses were determined by Ab level differences between W12 and W16. Secondary efficacy endpoints at W16 were Investigator Global Assessment (IGA) and Eczema Area and Severity Index (EASI 75) scores. Results: For Tdap, 73.6% of LEB patients had a positive Ab response vs 73.4% for PBO, 90% CI, 0.3 (-10.2, 11.2). For MCV, LEB patients had an 86.9% positive Ab response vs 75.0% for PBO, 90% CI, 12.2 (2.5, 22.0). IGA (0,1) was achieved by 40.6% of LEB patients vs 18.9% receiving PBO (p=<0.001); EASI 75 was achieved by 58.0% and 32.7% (p<0.001), respectively. The safety profile was consistent with previous LEB trials. Conclusions: These data show that LEB does not negatively impact immune responses for Tdap or MCV vaccines in adults with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Lebrikizumab (LEB) is a monoclonal antibody that binds with high affinity to interleukin (IL)-13, thereby blocking the downstream effects of IL-13 with high potency. To report integrated safety information in adult and adolescent patients with moderate-to-severe atopic dermatitis treated with LEB, from an integrated safety analysis of eight clinical Phase 2 and 3 trials. These data include adult and adolescent patients who received at least one dose of study drug from a total of eight atopic dermatitis clinical trials: ADvocate1, ADvocate2, ADhere, ADore, ADjoin (ongoing), ARBAN, TREBLE and a Phase 2b study. Treatment duration ranged from a single dose to 100 weeks. This analysis includes all placebo-controlled Week 0- to 16-safety data in patients treated with LEB 250 mg every 2 weeks (LEBQ2W, n = 783) compared with placebo (n = 404) known as ALL PC Weeks 0–16, and all patients who received at least one dose of LEB (n = 1720) known as ALL LEB. Conjunctivitis cluster is defined by MedDRA-preferred terms of conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis and giant papillary conjunctivitis. Exposure adjusted incidence rates (IR) are provided as per 100 patient-years. In ALL PC Weeks 0–16 analysis, the frequency of treatment-emergent adverse events (TEAE) was 49.2% in LEBQ2W (n = 384) compared with 53.1% in placebo (n = 215). The majority of TEAEs reported were mild or moderate in severity with 2.3% (n = 18) reported as severe in LEBQ2W and 4.4% (n = 18) in placebo. Serious adverse events (SAEs) were reported by 1.3% (n = 10) in LEBQ2W and 1.9% (n = 8) in placebo. No deaths reported in LEBQ2W and one death in placebo. The most frequently reported TEAE in LEBQ2W was conjunctivitis and in placebo was atopic dermatitis. Conjunctivitis cluster was reported by 8.5% (n = 67) in LEBQ2W and 2.5% (n = 10) in placebo. All conjunctivitis cluster events were mild or moderate. Injection site reactions (ISRs) were reported by 2.6% (n = 20) in LEBQ2W and 1.5% (n = 6) in placebo. Adverse events leading to discontinuation were reported by 2.3% (n = 18) in LEBQ2W and 1.4% (n = 6) in placebo. In ALL LEB, the frequency of TEAEs was 64.3% (n = 1106, IR: 137.9), with the majority being mild or moderate in severity. Severe TEAEs were reported by 5.3% (n = 91). The incidence rates of TEAE did not increase with duration of treatment exposure. The SAEs were reported by 3.3% (n = 56, IR: 3.5). Three (0.2%) deaths occurred in ALL LEB. Conjunctivitis cluster was reported by 10.6% (n = 183, IR:12.2) with the majority being mild or moderate in severity and 0.3% (n = 6) being reported as severe. The ISRs were reported by 3.1% (n = 53, IR: 3.3). Adverse events leading to discontinuation were reported by 4.2% (n = 73, IR: 4.5). The overall safety profile for lebrikizumab consisted of AEs that were mostly nonserious, mild or moderate in severity, and did not lead to treatment discontinuation. Safety profile was similar in both adults and adolescents. [ABSTRACT FROM AUTHOR]

Lebrikizumab (LEB) is a novel, high-affinity monoclonal anti - body that selectively binds to interleukin (IL)-13. To evaluate the efficacy and safety of LEB monotherapy in patients with moderate-to-severe atopic dermatitis (AD) in two identical phase 3 trials ADvocate1 (ADv1) and ADvocate2 (ADv2). Patients who responded to LEB 250 mg every 2 weeks (LEB Q2W) at the end of the 16-week induction period were re-randomized in a 2 : 2 :1 ratio to receive LEB Q2W, LEB 250 mg every 4 weeks (LEB Q4W) or placebo (LEB withdrawal) for an additional 36 weeks. Response, at week 16, was defined as achieving an IGA (0, 1) with a ≥2-point improvement or EASI75 and no use of rescue medication. Efficacy outcomes reported at week 52 included IGA (0, 1), EASI 75, ≥4-point reduction in Pruritis Numeric Rating Scale (NRS), EASI 90 and DLQI ≥4-point. Safety analysis was conducted on all patients who received ≥1 dose of LEB. Patients maintained IGA (0, 1) in LEB Q2W (ADv1, 75.8%; ADv2, 64.6%), LEB Q4W (ADv1, 74.2%; ADv2, 80.6%) and LEB withdrawal (ADv1, 46.5%; ADv2, 49.8%). Maintenance of EASI75 was, in LEB Q2W (ADv1, 79.2%; ADv2, 77.4%), LEB Q4W (ADv1, 79.2%; ADv2, 84.7%) and LEB withdrawal (ADv1, 61.3%; ADv2, 72.0%). For Pruritus NRS ≥4-point improvement from baseline, patients-maintained improvement in the LEB Q2W (ADv1, 81.2%; ADv2, 90.3%), LEB Q4W (ADv1, 80.4%; ADv2, 88.1%) and LEB withdrawal (ADv1, 65.4%; ADv2, 67.6%). Maintenance of EASI90 was, in LEB Q2W (ADv1, 66.1%; ADv2, 61.5%), LEB Q4W (ADv1, 66.6%; ADv2, 67.4%) and LEB withdrawal (ADv1, 45.5%; ADv2, 36.9%). DLQI ≥4-point improvement from baseline was LEB Q2W (ADv1, 64.0%; ADv2, 59.0%), LEB Q4W (ADv1, 62.7%; ADv2, 73.0%) and LEB withdrawal (ADv1, 57.7%; ADv2, 45.5%). TEAEs were reported by 58.1% (ADv1) and 67.8% (ADv2) LEB-treated patients at week 52. Serious adverse events were reported by 3.3% of ADv1 patients and 2.7% of ADv2 patients. In ADv1 and ADv2, 2.3% and 3.9% of patients reported an adverse event leading to treatment discontinuation, respectively. Both LEB Q2W and LEB Q4W maintained improvement in all reported outcomes for the treatment of moderate-to-severe AD through 52 weeks. The safety profile was consistent with previously published data. [ABSTRACT FROM AUTHOR]