Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial

Guttman‐Yassky, Emma; Brunner, Patrick M.; Neumann, Avidan U.; Khattri, Saakshi; Pavel, Ana B.; Malik, Kunal; Singer, Giselle; Baum, Danielle; Gilleaudeau, Patricia; Sullivan‐Whalen, Mary; Rose, Sharon; On, Shelbi Jim; Li, Xuan; Fuentes‐Duculan, Judilyn; Estrada, Yeriel; Garcet, Sandra; Traidl‐Hoffmann, Claudia; Krueger, James G.; Lebwohl, Mark

doi:10.1016/j.jaad.2018.01.016

Cited by 282 publications

(210 citation statements)

References 30 publications

Supporting

Mentioning

201

Contrasting

Unclassified

Order By: Relevance

“…Our results suggested that FAM13A is a positive regulator of IL-22 production by memory CD4 + T cells and thus females with higher expression of FAM13A are likely to have more pronounced IL-22 responses in vivo . IL-22 acts on epithelial cells to promote the release of anti-microbial peptides and chemokines as well as wound healing and regenerative gene programs, and thus plays an important role in barrier immunity as well as in promoting excessive inflammatory responses in skin diseases, where IL-22 blocking therapies have shown success (Guttman-Yassky et al, 2018). Recent studies have found that serum and sputum IL22 levels were elevated in patients with COPD (Zhang et al, 2013), implying IL-22 may also have a pathogenic role in COPD.…”

Section: Resultsmentioning

confidence: 99%

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

Schmiedel

Singh

Madrigal

et al. 2018

Cell

712

699

View full text Add to dashboard Cite

SUMMARY While many genetic variants have been associated with risk for human diseases, how these variants affect gene expression in various cell types remains largely unknown. To address this gap, the DICE (Database of Immune Cell Expression, Expression quantitative trait loci (eQTLs) and Epigenomics) project was established. Considering all human immune cell types and conditions studied, we identified cis-eQTLs for a total of 12,254 unique genes, which represent 61% of all protein-coding genes expressed in these cell types. Strikingly, a large fraction (41%) of these genes showed a strong cis-association with genotype only in a single cell type. We also found that biological sex is associated with major differences in immune cell gene expression in a highly cell-specific manner. These datasets will help reveal the effects of disease risk-associated genetic polymorphisms on specific immune cell types, providing mechanistic insights into how they might influence pathogenesis (http://dice-database.org).

show abstract

Section: Resultsmentioning

confidence: 99%

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

Schmiedel

Singh

Madrigal

et al. 2018

Cell

712

699

View full text Add to dashboard Cite

show abstract

“…Recent published phase 2 studies have demonstrated that the monoclonal antibodies that block IL-13 (lebrikizumab and tralokinumab) are effective in patients with moderate to severe AD [150, 151]. By applying fezakinumab, an anti-IL-22 antibody, a significant decline in disease severity scores (SCORAD, affected body surface area, and investigator global assessment), could be achieved and a pathogenic role for IL-22 in AD could be demonstrated [152]. Notably, therapy with ustekinumab that inhibits the common p40 subunit of IL-12/IL-23 and thus the production of IL-17, IL-21, and IL-22, was not effective in patients with moderate to very severe AD [153, 154].…”

Section: Therapeutic Management Of Admentioning

confidence: 99%

Atopic Dermatitis: Collegium Internationale Allergologicum (CIA) Update 2019

Simon

Wollenberg

Renz

et al. 2019

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Atopic dermatitis (AD) is a chronic inflammatory skin disease presenting with recurrent eczematous lesions and intense pruritus. It is common and affects both children and adults, often beginning in infancy. Due to the unpredictable disease course, its visible skin lesions, itching and scratching followed by sleeplessness, other associated atopic diseases, and behavioral and psychiatric disorders, AD is an immense burden for patients and caregivers. AD is determined by a genetic predisposition characterized by an impaired skin barrier and a T-helper-2-predominant inflammation. Restoration of the skin barrier is the main approach for treating and preventing AD. In order to cope with acute flares, usually topical corticosteroids (TCS) are applied, while topical calcineurin inhibitors (TCI) are used mainly for maintenance therapy. There is a small group of patients who are refractory to TCS and TCI and require systemic immunosuppressive drugs such as ciclosporin. Novel, targeted therapies are under clinical investigation, among which an anti-IL-4/IL-13 receptor antibody has recently been approved in several countries. As we learn to understand the pathomechanisms of AD, the characteristics of the different patient subgroups, and the effectiveness of various targeted therapies, a personalized treatment ensuring the best efficacy and safety and, probably, a disease-modifying effect will result.

show abstract

“…Fezakinumab, an IL-22 monoclonal antibody, showed efficacy only for severe AD (SCORAD ≥50) in a phase 2 clinical trial. 113 Another report suggested that fezakinumab may be more effected for patients with high baseline IL-22 expression. 114 Interestingly, selective targeting of some propruritogenic factors such as TSLP has shown mixed results in clinical testing.…”

Section: Biologic Agentsmentioning

confidence: 99%

Immune mediators and therapies for pruritus in atopic dermatitis and psoriasis

Zhou

et al. 2019

J Cutaneous Imm & Allergy

View full text Add to dashboard Cite

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractAtopic dermatitis (AD) and psoriasis (Pso) are two common inflammatory skin diseases which are symptomatically characterized by pruritus to variable degrees.Whereas AD is nearly always associated with pruritus, only 50%-70% of patients with Pso suffer from itching. Within the last decade, the development of biologic agents targeting specific cytokines or cytokine receptors has led to tremendous progress in suppressing inflammation (and thus improving quality of life) in these two diseases.While suppressing inflammation would generally reduce pruritus in these inflammatory diseases, pruritus is still recalcitrant for treatment in some patients due to relative lack of therapeutics that specifically inhibit pruritus signaling. There is abundant evidence that certain cytokines and neuropeptides-ion channels signaling mediate pruritus that is independent of inflammation in AD and psoriasis. Of note, Janus kinase (JAK) and nerve growth factor (NGF)-tropomyosin receptor kinase A (TrkA)transient receptor potential vanilloid 1 (TRPV1) signaling partially regulates pruritus in AD and psoriasis. JAK kinases inhibitors decrease the extent of itch in patients with AD and psoriasis. In clinical trials, topical inhibitors of TrkA and TRPV1 have been reported to reduce pruritus in patients with Pso and AD, respectively. In this article, we review recent literature knowledge regarding the mechanisms underlying pruritus in AD and Pso, providing hypotheses for why pruritus may be more common in AD than in Pso. In light of the different mechanisms underlying these two diseases, the current and developing therapeutics, either in human clinical trials or animal studies, for targeting pruritus are also discussed. K E Y W O R D SIL-31, neuropeptide, PAR2, SP, thymic stromal lymphopoietin, TRPA1, TRPV1

show abstract

Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial

Abstract: Fezakinumab was well-tolerated, with sustained clinical improvements after last drug dosing.

Cited by 282 publications

References 30 publications

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

Impact of Genetic Polymorphisms on Human Immune Cell Gene Expression

Atopic Dermatitis: Collegium Internationale Allergologicum (CIA) Update 2019

Immune mediators and therapies for pruritus in atopic dermatitis and psoriasis

Contact Info

Product

Resources

About