Atopic dermatitis

The Lancet, Journal Year: 2020, Volume and Issue: 396(10247), P. 345 - 360

Published: July 30, 2020

Language: Английский

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Atopic dermatitis: an expanding therapeutic pipeline for a complex disease

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 21(1), P. 21 - 40

Published: Aug. 20, 2021

Language: Английский

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Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial

The Lancet, Journal Year: 2020, Volume and Issue: 396(10246), P. 255 - 266

Published: July 1, 2020

Language: Английский

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ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2020, Volume and Issue: 34(12), P. 2717 - 2744

Published: Nov. 17, 2020

Abstract Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis made using evaluated clinical criteria. Disease activity and burden are best measured with composite score, assessing both objective subjective symptoms, such as SCORing Dermatitis (SCORAD). AD management must take into account pathogenic variabilities, the patient’s age also target flare prevention. Basic therapy includes hydrating barrier‐stabilizing topical treatment universally applied, well avoiding specific unspecific provocation factors. Visible lesions treated anti‐inflammatory agents corticosteroids calcineurin inhibitors (tacrolimus pimecrolimus), which preferred in sensitive locations. Topical tacrolimus some mid‐potency proven for proactive therapy, defined long‐term intermittent of frequently relapsing areas. Systemic or immunosuppressive rapidly changing field requiring monitoring. Oral have largely unfavourable benefit–risk ratio. IL‐4R‐blocker dupilumab safe, effective licensed, but expensive, option potential ocular side‐effects. Other biologicals targeting key pathways atopic immune response, different Janus kinase inhibitors, among emerging options. Dysbalanced microbial colonization infection may induce disease exacerbation can justify additional antimicrobial treatment. antihistamines (H1R‐blockers) only limited effects on AD‐related itch eczema lesions. Adjuvant UV irradiation, preferably narrowband UVB UVA1. Coal tar be useful hand foot eczema. Dietary recommendations should patient‐specific, elimination diets advised case food allergy. Allergen‐specific immunotherapy to aeroallergens selected cases. Psychosomatic counselling recommended address stress‐induced exacerbations. Efficacy‐proven 'Eczema school' educational programmes therapeutic patient education children adults.

Language: Английский

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Mechanisms of Dupilumab

Clinical & Experimental Allergy, Journal Year: 2019, Volume and Issue: 50(1), P. 5 - 14

Published: Sept. 10, 2019

The Th2 cytokines interleukin 4 (IL-4) and IL-13 the heterodimeric IL-4 receptor (IL-4R) complexes that they interact with play a key role in pathogenesis of allergic disorders. Dupilumab is humanized IgG4 monoclonal antibody targets alpha chain (IL-4Rα), common to both IL-4R complexes: type 1 (IL-4Rα/γc; specific) 2 (IL-4Rα/IL-13Rα1; specific). In this review, we detail current state knowledge different signalling pathways coupled examine possible mechanisms action survey its clinical efficacy development widening spectrum applications relevant emphasis on precision medicine approaches blockade involved diseases.

Language: Английский

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Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 384(12), P. 1101 - 1112

Published: March 24, 2021

The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block receptors are limited.In a phase 3, double-blind trial, we randomly assigned patients dermatitis was unresponsive to topical agents or warranted systemic therapy (in 2:2:2:1 ratio) receive 200 mg 100 abrocitinib orally once daily, 300 dupilumab subcutaneously every other week (after loading dose 600 mg), placebo; all received therapy. primary end points were an Investigator's Global Assessment (IGA) response (defined score 0 [clear] [almost clear] on IGA [scores range 4], improvement ≥2 baseline) Eczema Area Severity Index-75 (EASI-75) ≥75% baseline in EASI 72]) at 12. key secondary itch ≥4 Peak Pruritus Numerical Rating Scale 10]) 2 EASI-75 responses 16.A total 838 underwent randomization; 226 200-mg group, 238 100-mg 243 131 placebo group. An 12 observed 48.4% 36.6% 36.5% 14.0% group (P<0.001 both doses vs. placebo); 70.3%, 58.7%, 58.1%, 27.1%, respectively placebo). dose, but not superior respect 2. Neither differed significantly most end-point comparisons 16. Nausea occurred 11.1% 4.2% those acne 6.6% 2.9%, respectively.In this either daily resulted greater reductions signs symptoms moderate-to-severe than weeks (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).

Language: Английский

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Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis

JAMA Dermatology, Journal Year: 2020, Volume and Issue: 156(8), P. 863 - 863

Published: June 3, 2020

Abrocitinib, an oral, once-daily Janus kinase 1 selective inhibitor, was effective and well tolerated in a phase 3 monotherapy trial of patients with moderate-to-severe atopic dermatitis (AD).To investigate the efficacy safety abrocitinib adolescents adults AD identically designed trial.This 3, double-blinded, placebo-controlled, parallel-group randomized clinical included 12 years or older diagnosis for at least year inadequate response to topical medications given 4 weeks within 6 months. Patients were enrolled from 115 centers Australia, Bulgaria, Canada, China, Czechia, Germany, Hungary, Japan, South Korea, Latvia, Poland, United Kingdom, States June 29, 2018, August 13, 2019. Data analyzed September 13 October 25, 2019.Patients randomly assigned (2:2:1) receive oral 200- 100-mg doses placebo weeks.The coprimary end points proportion achieving Investigator Global Assessment (IGA) (ie, clear [0] almost [1], improvement ≥2 grades) 75% Eczema Area Severity Index score (EASI-75) week 12. Key secondary Peak Pruritus Numerical Rating Scale (PP-NRS) ≥4 points) Other 90% EASI (EASI-90). Safety assessed via adverse events laboratory monitoring.A total 391 (229 male [58.6%]; mean [SD] age, 35.1 [15.1] years) analysis; these, 155 received abrocitinib, 200 mg/d; 158, 100 78, placebo. Among available data 12, greater proportions groups vs group achieved IGA (59 [38.1%] 44 [28.4%] 7 77 [9.1%]; P < .001) EASI-75 (94 154 [61.0%] 69 [44.5%] 8 [10.4%]; .001), estimated PP-NRS (55.3% [95% CI, 47.2%-63.5%] 45.2% 37.1%-53.3%] 11.5% 4.1%-19.0%]; and/or EASI-90 (58 [37.7%] 37 [23.9%] [3.9%]) responses. Adverse reported 102 (65.8%) 200-mg group, 99 (62.7%) 42 (53.8%) group; serious 2 (1.3%) 5 (3.2%) group. Decreases platelet count (2 [1.3%]) values indicating thrombocytopenia (5 [3.2%]) group.Monotherapy AD.ClinicalTrials.gov Identifier: NCT03575871.

Language: Английский

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Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: A randomized, double-blinded, placebo-controlled phase 3 trial

Journal of the American Academy of Dermatology, Journal Year: 2020, Volume and Issue: 83(5), P. 1282 - 1293

Published: June 20, 2020

Children with severe atopic dermatitis (AD) have limited treatment options.We report the efficacy and safety of dupilumab + topical corticosteroids (TCS) in children aged 6-11 years AD inadequately controlled therapies.In this double-blind, 16-week, phase 3 trial (NCT03345914), 367 patients were randomized 1:1:1 to 300 mg every 4 weeks (300 q4w), a weight-based regimen 2 (100 q2w, baseline weight <30 kg; 200 ≥30 kg), or placebo; concomitant medium-potency TCS.Both q4w q2w TCS regimens resulted clinically meaningful statistically significant improvement signs, symptoms, quality life (QOL) versus placebo all prespecified endpoints. For q4w, placebo, 32.8%, 29.5%, 11.4% patients, respectively, achieved Investigator's Global Assessment scores 0 1; 69.7%, 67.2%, 26.8% ≥75% Eczema Area Severity Index scores; 50.8%, 58.3%, 12.3% ≥4-point reduction worst itch score. Response therapy was weight-dependent: optimal doses for kg kg. Conjunctivitis injection-site reactions more common than TCS.Short-term 16-week period; only.Dupilumab is efficacious well tolerated AD, significantly improving QOL.

Language: Английский

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Interleukin‐13: Targeting an underestimated cytokine in atopic dermatitis

Allergy, Journal Year: 2019, Volume and Issue: 75(1), P. 54 - 62

Published: June 23, 2019

Abstract Atopic dermatitis (AD) is a common inflammatory skin condition that has traditionally been considered paradigmatic type 2 immunity (T2)‐driven disease. Interleukin (IL)‐4 and IL‐13 are both pivotal cytokines involved in the generation of allergic diseases. Currently, besides dupilumab, which blocks binding to their receptors, number new pharmacologic entities have designed target T2 and/or receptors receptor‐associated signal transduction machinery such as Janus kinases. Recently, suggested be key cytokine driving inflammation periphery, while IL‐4 may merely central effect. There increasing evidence this concept holds true for reaction underlying AD, where overexpressed locally significant impact on biology, including recruitment cells, alteration microbiome, decrease epidermal barrier function. This review provides an update role AD discusses different strategies aimed at interfering with its biologic activity well potential precision medicine approach management AD.

Language: Английский

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European guideline (EuroGuiDerm) on atopic eczema: part I – systemic therapy

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2022, Volume and Issue: 36(9), P. 1409 - 1431

Published: Aug. 18, 2022

Abstract The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline Consensus Statement Development Manual. Four consensus conferences were held between December 2020 July 2021. Twenty‐nine experts (including clinicians patient representatives) from 12 European countries participated. This first part of includes general information its scope purpose, health questions covered, target users a methods section. It also provides guidance which patients should be treated systemic therapies, as well recommendations detailed each drug. treatment options discussed comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab tralokinumab) janus kinase inhibitors (abrocitinib, baricitinib upadacitinib). Part two will address avoidance provocation factors, dietary interventions, immunotherapy, complementary medicine, educational occupational psychodermatological aspects, perspective considerations for paediatric, adolescent, pregnant breastfeeding patients.

Language: Английский

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