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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Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis

Journal of Allergy and Clinical Immunology, Journal Year: 2018, Volume and Issue: 143(1), P. 155 - 172

Published: Sept. 5, 2018

Dupilumab is an IL-4 receptor α mAb inhibiting signaling of and IL-13, key drivers type 2-driven inflammation, as demonstrated by its efficacy in patients with atopic/allergic diseases.This placebo-controlled, double-blind trial (NCT01979016) evaluated the efficacy, safety, effects dupilumab on molecular/cellular lesional nonlesional skin phenotypes systemic 2 biomarkers moderate-to-severe atopic dermatitis (AD).Skin biopsy specimens blood were from 54 randomized 1:1 to weekly subcutaneous doses 200 mg or placebo for 16 weeks.Dupilumab (vs placebo) significantly improved clinical signs symptoms AD, was well tolerated, progressively shifted transcriptome toward a phenotype (weeks 4-16). Mean improvements meta-analysis-derived AD (genes differentially expressed between skin) 68.8% 110.8% -10.5% 55.0% 4 16, respectively; P < .001). reduced expression genes involved inflammation (IL13, IL31, CCL17, CCL18, CCL26), epidermal hyperplasia (keratin [K16] MKi67), T cells, dendritic cells (ICOS, CD11c, CTLA4), TH17/TH22 activity (IL17A, IL-22, S100As) concurrently increased differentiation, barrier, lipid metabolism (filaggrin [FLG], loricrin [LOR], claudins, ELOVL3). thickness versus (week 4, = .001; week .0002). Improvements histologic measures correlated modulation gene expression. also suppressed serum biomarkers, including periostin, total allergen-specific IgEs.Dupilumab-mediated inhibition IL-4/IL-13 through blockade disease activity, cellular/molecular cutaneous markers reversed AD-associated abnormalities.

Language: Английский

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Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis

JAMA Dermatology, Journal Year: 2019, Volume and Issue: 156(1), P. 44 - 44

Published: Nov. 6, 2019

Adolescents with atopic dermatitis (AD) have high disease burden negatively affecting quality of life, limited treatment options. The efficacy and safety dupilumab, a monoclonal antibody, approved for in adolescent patients inadequately controlled AD, remain unknown this patient population.

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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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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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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Conjunctivitis in dupilumab clinical trials

British Journal of Dermatology, Journal Year: 2019, Volume and Issue: 181(3), P. 459 - 473

Published: March 9, 2019

Dupilumab blocks the shared receptor component for interleukin (IL)‐4 and IL‐13. It is approved in U.S.A. patients aged ≥ 12 years with moderate‐to‐severe atopic dermatitis (AD) uncontrolled by topical prescription medicines or who cannot use medicines, Japan whose AD existing therapies, Europe are candidates systemic therapy maintenance treatment of asthma their current medicines. trials have reported increased incidence conjunctivitis dupilumab vs. placebo. To characterize further occurrence risk factors clinical trials. We evaluated randomized placebo‐controlled (n = 2629), 2876), chronic rhinosinusitis nasal polyps (CRSwNP) 60) eosinophilic oesophagitis (EoE) 47). In most trials, dupilumab‐treated had higher than placebo controls. Higher baseline severity previous history were associated incidence. Conjunctivitis was mostly mild to moderate. Most cases recovered resolved during period; two permanently discontinued due keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, antihistamines mast cell stabilizers. diagnosed investigators. CRSwNP lower both trials; did not increase compared EoE trial, no conjunctivitis. more frequent other type 2 diseases, overall very low, similar AD, prior The aetiology require study. What's already known about this topic? Ocular disorders, including allergic conjunctivitis, common (AD). those receiving moderate recovering study treatment; discontinuation rare. low asthma, oesophagitis. What does add? This analysis confirms extends results individual Baseline disease‐related factors, severity, certain biomarkers (thymus activation‐regulated chemokine, IgE, eosinophils), Patients responded well reduced Further needed elucidate AD.

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 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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Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study

Journal of the American Academy of Dermatology, Journal Year: 2019, Volume and Issue: 82(2), P. 377 - 388

Published: July 30, 2019

Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD).To assess the safety and efficacy dupilumab in patients with AD.This ongoing, multicenter, open-label extension study (NCT01949311) evaluated adults who had previously participated phase 1 through 3 clinical trials AD. This analysis examined given 300 mg weekly up 76 weeks at data cutoff (April 2016). Safety was primary outcome; also evaluated.Of 1491 enrolled (1042.9 patient-years), 92.9% were receiving cutoff. The profile consistent reported (420.4 adverse events/100 patient-years 8.5 serious no new signals; common events included nasopharyngitis, conjunctivitis, injection-site reactions. Sustained improvement seen all outcomes, including measures skin inflammation, pruritus, quality life.Lack control arm, limited number or longer (median follow-up, 24 weeks), not approved dose regimen every 2 weeks.The from this supports role as continuous

Language: Английский

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