Type 2 chronic inflammatory diseases: targets, therapies and unmet needs.
Journal
Nature reviews. Drug discovery
ISSN: 1474-1784
Titre abrégé: Nat Rev Drug Discov
Pays: England
ID NLM: 101124171
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
accepted:
16
06
2023
medline:
4
9
2023
pubmed:
2
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
Over the past two decades, significant progress in understanding of the pathogenesis of type 2 chronic inflammatory diseases has enabled the identification of compounds for more than 20 novel targets, which are approved or at various stages of development, finally facilitating a more targeted approach for the treatment of these disorders. Most of these newly identified pathogenic drivers of type 2 inflammation and their corresponding treatments are related to mast cells, eosinophils, T cells, B cells, epithelial cells and sensory nerves. Epithelial barrier defects and dysbiotic microbiomes represent exciting future drug targets for chronic type 2 inflammatory conditions. Here, we review common targets, current treatments and emerging therapies for the treatment of five major type 2 chronic inflammatory diseases - atopic dermatitis, chronic prurigo, chronic urticaria, asthma and chronic rhinosinusitis with nasal polyps - with a high need for targeted therapies. Unmet needs and future directions in the field are discussed.
Identifiants
pubmed: 37528191
doi: 10.1038/s41573-023-00750-1
pii: 10.1038/s41573-023-00750-1
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
743-767Informations de copyright
© 2023. Springer Nature Limited.
Références
Chensue, S. W. et al. Role of monocyte chemoattractant protein-1 (MCP-1) in T
pubmed: 8906839
Akdis, C. A. et al. Type 2 immunity in the skin and lungs. Allergy 75, 1582–1605 (2020).
pubmed: 32319104
Akdis, C. A. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat. Rev. Immunol. 21, 739–751 (2021). This comprehensive review discusses how the immune responses to dysbiotic microbiota that cross the damaged epithelial barrier may be involved in the development of type 2 diseases and other conditions.
pubmed: 33846604
Zuberbier, T. et al. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria. Allergy 77, 734–766 (2022).
pubmed: 34536239
Global Initiative for Asthma. 2022 GINA report, global strategy for asthma management and prevention (2022 Update). Global Initiative for Asthma https://ginasthma.org/gina-reports (2022).
GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396, 1204–1222 (2020).
Kolkhir, P. et al. Urticaria. Nat. Rev. Dis. Prim. 8, 61 (2022). This Primer presents an overview of the epidemiology, pathogenesis, diagnosis and treatment of urticaria including the recent development of targeted treatments.
pubmed: 36109590
Zuberbier, T., Lötvall, J., Simoens, S., Subramanian, S. V. & Church, M. K. Economic burden of inadequate management of allergic diseases in the European Union: a GA
pubmed: 24965386
Bantz, S. K., Zhu, Z. & Zheng, T. The atopic march: progression from atopic dermatitis to allergic rhinitis and asthma. J. Clin. Cell. Immunol. 5, 202 (2014).
pubmed: 25419479
pmcid: 4240310
Gough, H. et al. Allergic multimorbidity of asthma, rhinitis and eczema over 20 years in the German birth cohort MAS. Pediatr. Allergy Immunol. 26, 431 (2015).
pubmed: 26011739
pmcid: 4744942
Maurer, M. et al. The burden of chronic spontaneous urticaria is substantial: real-world evidence from ASSURE-CSU. Allergy 72, 2005–2016 (2017).
pubmed: 28543019
Ariëns, L. F. M. et al. Economic burden of adult patients with moderate to severe atopic dermatitis indicated for systemic treatment. Acta Derm. Venereol. 99, 762–768 (2019).
pubmed: 31073619
Weidinger, S., Beck, L. A., Bieber, T., Kabashima, K. & Irvine, A. D. Atopic dermatitis. Nat. Rev. Dis. Prim. 4, 1 (2018).
pubmed: 29930242
Bieber, T. Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat. Rev. Drug Discov. 21, 21–40 (2022). This Review focuses on novel targeted treatments and strategies in development in AD.
pubmed: 34417579
Agache, I. et al. EAACI Biologicals Guidelines — dupilumab for children and adults with moderate-to-severe atopic dermatitis. Allergy 76, 988–1009 (2021).
pubmed: 33538044
Ständer, S. et al. IFSI-guideline on chronic prurigo including prurigo nodularis. Itch 5, e42 (2020).
Labib, A., Ju, T., Vander Does, A. & Yosipovitch, G. Immunotargets and therapy for prurigo nodularis. Immunotargets Ther. 11, 11–21 (2022).
pubmed: 35502157
pmcid: 9056055
Elmariah, S. et al. Practical approaches for diagnosis and management of prurigo nodularis: United States expert panel consensus. J. Am. Acad. Dermatol. 84, 747–760 (2021).
pubmed: 32682025
Agache, I. et al. EAACI Biologicals Guidelines — recommendations for severe asthma. Allergy 76, 14–44 (2021).
pubmed: 32484954
Annunziato, F., Romagnani, C. & Romagnani, S. The 3 major types of innate and adaptive cell-mediated effector immunity. J. Allergy Clin. Immunol. 135, 626–635 (2015).
pubmed: 25528359
Busse, W. W. et al. Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation. Eur. Respir. J. 58, 2003393 (2021).
pubmed: 33542055
pmcid: 8339540
Agache, I. et al. Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: a systematic review for the EAACI guidelines. Allergy 76, 2337–2353 (2021).
pubmed: 33683704
Bachert, C., Maurer, M., Palomares, O. & Busse, W. W. What is the contribution of IgE to nasal polyposis? J. Allergy Clin. Immunol. 147, 1997–2008 (2021).
pubmed: 33757720
Stevens, W. W. et al. Associations between inflammatory endotypes and clinical presentations in chronic rhinosinusitis. J. Allergy Clin. Immunol. Pract. 7, 2812–2820.e3 (2019).
pubmed: 31128376
pmcid: 6842686
Sanchez-Collado, I. et al. Prevalence of chronic rhinosinusitis with nasal polyps in catalonia (Spain): a retrospective, large-scale population-based study. Rhinology 60, 384–396 (2022).
pubmed: 36150155
Tomassen, P. et al. Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers. J. Allergy Clin. Immunol. 137, 1449–14564 (2016).
pubmed: 26949058
Orlandi, R. R. et al. International consensus statement on allergy and rhinology: rhinosinusitis 2021. Int. Forum Allergy Rhinol. 11, 213–739 (2021).
pubmed: 33236525
Wollenberg, A. et al. European guideline (EuroGuiDerm) on atopic eczema — part II: non-systemic treatments and treatment recommendations for special AE patient populations. J. Eur. Acad. Dermatol. Venereol. 36, 1904–1926 (2022).
pubmed: 36056736
Wollenberg, A. et al. European guideline (EuroGuiDerm) on atopic eczema: part I — systemic therapy. J. Eur. Acad. Dermatol. Venereol. 36, 1409–1431 (2022).
pubmed: 35980214
Gandhi, N. A. et al. Targeting key proximal drivers of type 2 inflammation in disease. Nat. Rev. Drug Discov. 15, 35–50 (2016). This publication reviews key proximal drivers of type 2 inflammation and treatments that target them focusing mostly on asthma, AD and CRSwNP.
pubmed: 26471366
Galli, S. J. & Tsai, M. IgE and mast cells in allergic disease. Nat. Med. 18, 693 (2012).
pubmed: 22561833
pmcid: 3597223
Giménez-Arnau, A. M. et al. The pathogenesis of chronic spontaneous urticaria: the role of infiltrating cells. J. Allergy Clin. Immunol. Pract. 9, 2195–2208 (2021).
pubmed: 33823316
Roan, F., Obata-Ninomiya, K. & Ziegler, S. F. Epithelial cell-derived cytokines: more than just signaling the alarm. J. Clin. Invest. 129, 1441–1451 (2019).
pubmed: 30932910
pmcid: 6436879
Akdis, M. et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: receptors, functions, and roles in diseases. J. Allergy Clin. Immunol. 138, 984–1010 (2016). This paper extensively discusses developments on interleukins, TNF, TGFβ and interferons including cellular sources, targets, receptors, signalling pathways and roles in immune regulation in patients with inflammatory diseases.
pubmed: 27577879
Gauvreau, G. M., Sehmi, R., Ambrose, C. S. & Griffiths, J. M. Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert. Opin. Ther. Targets 24, 777–792 (2020).
pubmed: 32567399
Sozener, Z. C. et al. Epithelial barrier hypothesis: effect of the external exposome on the microbiome and epithelial barriers in allergic disease. Allergy 77, 1418–1449 (2022).
Palomares, O., Akdis, M., Martin-Fontecha, M. & Akdis, C. A. Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells. Immunol. Rev. 278, 219–236 (2017).
pubmed: 28658547
Reginald, K. et al. Immunoglobulin E antibody reactivity to bacterial antigens in atopic dermatitis patients. Clin. Exp. Allergy 41, 357–369 (2011).
pubmed: 21155910
Zhong, W. et al. Aberrant expression of histamine-independent pruritogenic mediators in keratinocytes may be involved in the pathogenesis of prurigo nodularis. Acta Derm. Venereol. 99, 579–586 (2019).
pubmed: 30809683
Soumelis, V. et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 3, 673–680 (2002).
pubmed: 12055625
Kay, A. B., Clark, P., Maurer, M. & Ying, S. Elevations in T-helper-2-initiating cytokines (interleukin-33, interleukin-25 and thymic stromal lymphopoietin) in lesional skin from chronic spontaneous (‘idiopathic’) urticaria. Br. J. Dermatol. 172, 1294–1302 (2015).
pubmed: 25523947
Sugita, K. et al. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients. J. Allergy Clin. Immunol. 141, 300–310.e11 (2018).
pubmed: 28392332
Kast, J. I. et al. Respiratory syncytial virus infection influences tight junction integrity. Clin. Exp. Immunol. 190, 351–359 (2017).
pubmed: 28856667
pmcid: 5680068
Tan, H. T. et al. Tight junction, mucin, and inflammasome-related molecules are differentially expressed in eosinophilic, mixed, and neutrophilic experimental asthma in mice. Allergy 74, 294–307 (2019).
pubmed: 30267575
Wang, M. et al. Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells. J. Allergy Clin. Immunol. 143, 1892–1903 (2019).
pubmed: 30500342
Palomares, O. et al. dIvergEnt: how IgE axis contributes to the continuum of allergic asthma and anti-IgE therapies. Int. J. Mol. Sci. 18, 1328 (2017).
pubmed: 28635659
pmcid: 5486149
Toki, S. et al. TSLP and IL-33 reciprocally promote each other’s lung protein expression and ILC2 receptor expression to enhance innate type-2 airway inflammation. Allergy 75, 1606–1617 (2020).
pubmed: 31975538
An, G. et al. Combined blockade of IL-25, IL-33 and TSLP mediates amplified inhibition of airway inflammation and remodelling in a murine model of asthma. Respirology 25, 603–612 (2020).
pubmed: 31610614
Li, Y. et al. Elevated expression of IL-33 and TSLP in the airways of human asthmatics in vivo: a potential biomarker of severe refractory disease. J. Immunol. 200, 2253–2262 (2018).
pubmed: 29453280
Soyka, M. B. et al. Defective epithelial barrier in chronic rhinosinusitis: the regulation of tight junctions by IFN-γ and IL-4. J. Allergy Clin. Immunol. 130, 1087–1096.e10 (2012).
pubmed: 22840853
Jiao, J. et al. Transforming growth factor-β1 decreases epithelial tight junction integrity in chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol. 141, 1160–1163.e9 (2018).
pubmed: 29132958
Altunbulakli, C. et al. Staphylococcus aureus enhances the tight junction barrier integrity in healthy nasal tissue, but not in nasal polyps. J. Allergy Clin. Immunol. 142, 665–668.e8 (2018).
pubmed: 29518417
Liao, B. et al. Interaction of thymic stromal lymphopoietin, IL-33, and their receptors in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps. Allergy 70, 1169–1180 (2015).
pubmed: 26095319
Nagarkar, D. R. et al. Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis. J. Allergy Clin. Immunol. 132, 593–600.e12 (2013).
pubmed: 23688414
pmcid: 3759596
Zielińska-Bliźniewska, H. et al. Serum IL-5, POSTN and IL-33 levels in chronic rhinosinusitis with nasal polyposis correlate with clinical severity. BMC Immunol. 23, 33 (2022).
pubmed: 35752781
pmcid: 9233770
Pelaia, C. et al. Interleukins 4 and 13 in asthma: key pathophysiologic cytokines and druggable molecular targets. Front. Pharmacol. 13, 851940 (2022).
pubmed: 35350765
Yosipovitch, G., Rosen, J. D. & Hashimoto, T. Itch: from mechanism to (novel) therapeutic approaches. J. Allergy Clin. Immunol. 142, 1375–1390 (2018).
pubmed: 30409247
Humeau, M., Boniface, K. & Bodet, C. Cytokine-mediated crosstalk between keratinocytes and T cells in atopic dermatitis. Front. Immunol. 13, 801579 (2022).
pubmed: 35464457
pmcid: 9022745
Chiricozzi, A., Maurelli, M., Peris, K. & Girolomoni, G. Targeting IL-4 for the treatment of atopic dermatitis. Immunotargets Ther. 9, 151–156 (2020).
pubmed: 33062619
pmcid: 7532907
Honzke, S. et al. Influence of T
pubmed: 27015451
Meisser, S. S. et al. Skin barrier damage after exposure to paraphenylenediamine. J. Allergy Clin. Immunol. 145, 619–631.e2 (2020).
pubmed: 31783056
Renert-Yuval, Y. et al. Tape strips capture atopic dermatitis-related changes in nonlesional skin throughout maturation. Allergy 77, 3445–3447 (2022).
pubmed: 35775320
De Benedetto, A. et al. Tight junction defects in patients with atopic dermatitis. J. Allergy Clin. Immunol. 127, 773–786.e1–e7 (2011).
pubmed: 21163515
Sugita, K. et al. Human type 2 innate lymphoid cells disrupt skin keratinocyte tight junction barrier by IL-13. Allergy 74, 2534–2537 (2019).
pubmed: 31166013
Berdyshev, E. et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight 3, e98006 (2018).
pubmed: 29467325
pmcid: 5916244
Berdyshev, E. et al. Dupilumab significantly improves skin barrier function in patients with moderate-to-severe atopic dermatitis. Allergy 77, 3388–3397 (2022).
pubmed: 35815904
Altunbulakli, C. et al. Relations between epidermal barrier dysregulation and Staphylococcus species-dominated microbiome dysbiosis in patients with atopic dermatitis. J. Allergy Clin. Immunol. 142, 1643–1647.e12 (2018).
pubmed: 30048670
Trautmann, A. et al. T cell-mediated Fas-induced keratinocyte apoptosis plays a key pathogenetic role in eczematous dermatitis. J. Clin. Invest. 106, 25–35 (2000).
pubmed: 10880045
pmcid: 517909
Brunner, P. M. et al. Early-onset pediatric atopic dermatitis is characterized by T
pubmed: 29731129
Sanyal, R. D. et al. Atopic dermatitis in African American patients is T
pubmed: 30223113
Noda, S. et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased T
pubmed: 26428954
Zimmermann, M. et al. TWEAK and TNF-α cooperate in the induction of keratinocyte apoptosis. J. Allergy Clin. Immunol. 127, 200–207 (2011).
pubmed: 21211655
Mashiko, S. et al. Human mast cells are major IL−22 producers in patients with psoriasis and atopic dermatitis. J. Allergy Clin. Immunol. 136, 351–391 (2015).
pubmed: 25792465
Sutaria, N. et al. Cutaneous transcriptomics identifies fibroproliferative and neurovascular gene dysregulation in prurigo nodularis compared with psoriasis and atopic dermatitis. J. Invest. Dermatol. 142, 2537–2540 (2022).
pubmed: 35257721
pmcid: 9391257
Park, K., Mori, T., Nakamura, M. & Tokura, Y. Increased expression of mRNAs for IL-4, IL-17, IL-22 and IL-31 in skin lesions of subacute and chronic forms of prurigo. Eur. J. Dermatol. 21, 135–136 (2011).
pubmed: 21227892
Parthasarathy, V. et al. Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: a cluster analysis. Front. Med. 9, 1011142 (2022).
Fukushi, S., Yamasaki, K. & Aiba, S. Nuclear localization of activated STAT6 and STAT3 in epidermis of prurigo nodularis. Br. J. Dermatol. 165, 990–996 (2011).
pubmed: 21711341
Oetjen, L. K. et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell 171, 217–228.e13 (2017).
pubmed: 28890086
pmcid: 5658016
Chiricozzi, A. et al. Dupilumab improves clinical manifestations, symptoms, and quality of life in adult patients with chronic nodular prurigo. J. Am. Acad. Dermatol. 83, 39–45 (2020).
pubmed: 32229281
Campion, M. et al. Interleukin-4 and interleukin-13 evoke scratching behaviour in mice. Exp. Dermatol. 28, 1501–1504 (2019).
pubmed: 31505056
Nguyen, J. K., Austin, E., Huang, A., Mamalis, A. & Jagdeo, J. The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch. Dermatol. Res. 312, 81–92 (2020).
pubmed: 31493000
Manson, M. L. et al. IL-13 and IL-4, but not IL−5 nor IL-17A, induce hyperresponsiveness in isolated human small airways. J. Allergy Clin. Immunol. 145, 808–817.e2 (2020).
pubmed: 31805312
Yee, K. K. et al. Neuropathology of the olfactory mucosa in chronic rhinosinusitis. Am. J. Rhinol. Allergy 24, 110–120 (2010).
pubmed: 20021743
Maina, I. W., Patel, N. N. & Cohen, N. A. Understanding the role of biofilms and superantigens in chronic rhinosinusitis. Curr. Otorhinolaryngol. Rep. 6, 253–262 (2018).
pubmed: 30859016
pmcid: 6407876
Takabayashi, T. et al. Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol. 132, 584–592.e4 (2013).
pubmed: 23541322
pmcid: 3737402
Takabayashi, T. & Schleimer, R. P. Formation of nasal polyps: the roles of innate type 2 inflammation and deposition of fibrin. J. Allergy Clin. Immunol. 145, 740–750 (2020).
pubmed: 32145873
pmcid: 7263055
Pelaia, C. et al. Interleukin-5 in the pathophysiology of severe asthma. Front. Physiol. 10, 1514 (2019).
pubmed: 31920718
pmcid: 6927944
Motojima, S., Akutsu, I., Fukuda, T., Makino, S. & Takatsu, K. Clinical significance of measuring levels of sputum and serum ECP and serum IL-5 in bronchial asthma. Allergy 48, 98–106 (1993).
pubmed: 8109721
Li, W. et al. Periostin: its role in asthma and its potential as a diagnostic or therapeutic target. Respir. Res. 16, 57 (2015).
pubmed: 25981515
pmcid: 4437675
Flood-Page, P. et al. Anti-IL−5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J. Clin. Invest. 112, 1029–1036 (2003).
pubmed: 14523040
pmcid: 198522
Bachert, C., Wagenmann, M., Hauser, U. & Rudack, C. IL-5 synthesis is upregulated in human nasal polyp tissue. J. Allergy Clin. Immunol. 99, 837–842 (1997).
pubmed: 9215253
Gevaert, P. et al. The roles of eosinophils and interleukin-5 in the pathophysiology of chronic rhinosinusitis with nasal polyps. Int. Forum Allergy Rhinol. 12, 1413–1423 (2022).
pubmed: 35243803
pmcid: 9790271
Barretto, K. T. et al. Human airway epithelial cells express a functional IL-5 receptor. Allergy 75, 2127–2130 (2020).
pubmed: 32246831
Saitoh, T. et al. Relationship between epithelial damage or basement membrane thickness and eosinophilic infiltration in nasal polyps with chronic rhinosinusitis. Rhinology 47, 275–279 (2009).
pubmed: 19839250
Huang, I. H., Chung, W. H., Wu, P. C. & Chen, C. B. JAK–STAT signaling pathway in the pathogenesis of atopic dermatitis: an updated review. Front. Immunol. 13, 1068260 (2022).
pubmed: 36569854
pmcid: 9773077
Philips, R. L. et al. The JAK–STAT pathway at 30: much learned, much more to do. Cell 185, 3857–3876 (2022). This publication summarizes the current state of knowledge of the JAK–STAT pathway.
pubmed: 36240739
pmcid: 9815833
Mendes-Bastos, P. et al. Bruton’s tyrosine kinase inhibition — an emerging therapeutic strategy in immune-mediated dermatological conditions. Allergy 77, 2355–2366 (2022).
pubmed: 35175630
Phillips, J. E. et al. Btk inhibitor RN983 delivered by dry powder nose-only aerosol inhalation inhibits bronchoconstriction and pulmonary inflammation in the ovalbumin allergic mouse model of asthma. J. Aerosol Med. Pulm. Drug Deliv. 29, 233–241 (2016).
pubmed: 27111445
pmcid: 5248542
Leung, D. Y. Role of IgE in atopic dermatitis. Curr. Opin. Immunol. 5, 956–962 (1993).
pubmed: 8297530
Altrichter, S. et al. Serum IgE autoantibodies target keratinocytes in patients with atopic dermatitis. J. Invest. Dermatol. 128, 2232–2239 (2008).
pubmed: 18480840
Müller, S., Bieber, T. & Ständer, S. Therapeutic potential of biologics in prurigo nodularis. Expert. Opin. Biol. Ther. 22, 47–58 (2022).
pubmed: 34289753
Xiang, Y.-K. et al. Most patients with autoimmune chronic spontaneous urticaria also have autoallergic urticaria, but not vice versa. J. Allergy Clin. Immunol. Pract. S2213-2198, 00184–00188 (2023).
Schoepke, N. et al. Biomarkers and clinical characteristics of autoimmune chronic spontaneous urticaria: results of the PURIST study. Allergy 74, 2427–2436 (2019).
pubmed: 31228881
Kolkhir, P. et al. Autoimmune chronic spontaneous urticaria. J. Allergy Clin. Immunol. 149, 1819–1831 (2022).
pubmed: 35667749
Schmetzer, O. et al. IL-24 is a common and specific autoantigen of IgE in patients with chronic spontaneous urticaria. J. Allergy Clin. Immunol. 142, 876–882 (2018).
pubmed: 29208545
Shen, Y., Zhang, N., Yang, Y., Hong, S. & Bachert, C. Local immunoglobulin E in nasal polyps: role and modulation. Front. Immunol. 13, 961503 (2022).
pubmed: 36159836
pmcid: 9492990
Shamji, M. H. et al. Broad IgG repertoire in patients with chronic rhinosinusitis with nasal polyps regulates proinflammatory IgE responses. J. Allergy Clin. Immunol. 143, 2086–2094.e2 (2019).
pubmed: 30763592
Altrichter, S. et al. The role of eosinophils in chronic spontaneous urticaria. J. Allergy Clin. Immunol. 145, 1510–1516 (2020).
pubmed: 32224275
Kolkhir, P., Elieh-Ali-Komi, D., Metz, M., Siebenhaar, F. & Maurer, M. Understanding human mast cells: lesson from therapies for allergic and non-allergic diseases. Nat. Rev. Immunol. 22, 294–308 (2022). This Review discusses mast cell-targeted treatments and how these therapies can help us understand mast cell functions in disease.
pubmed: 34611316
Fujisawa, D. et al. Expression of mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria. J. Allergy Clin. Immunol. 134, 622–633.e9 (2014).
pubmed: 24954276
Yanase, Y., Takahagi, S., Ozawa, K. & Hide, M. The role of coagulation and complement factors for mast cell activation in the pathogenesis of chronic spontaneous urticaria. Cells 10, 1759 (2021).
pubmed: 34359930
pmcid: 8306267
Maric, J. et al. Cytokine-induced endogenous production of prostaglandin D
pubmed: 30578872
Xue, L. et al. Prostaglandin D
pubmed: 24388011
pmcid: 3979107
Takabayashi, T. et al. Glandular mast cells with distinct phenotype are highly elevated in chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol. 130, 410–412.e5 (2012).
pubmed: 22534535
pmcid: 3408832
Hashimoto, T. et al. Itch intensity in prurigo nodularis is closely related to dermal interleukin-31, oncostatin M, IL-31 receptor α and oncostatin M receptor β. Exp. Dermatol. 30, 804–810 (2021).
pubmed: 33428793
Wang, F., Yang, T. B. & Kim, B. S. The return of the mast cell: new roles in neuroimmune itch. Biol. J. Invest. Dermatol. 140, 945–951 (2020).
Kolkhir, P. et al. Mast cells, cortistatin, and its receptor, MRGPRX2, are linked to the pathogenesis of chronic prurigo. J. Allergy Clin. Immunol. 149, 1998–2009.e5 (2022).
pubmed: 35283140
Kabata, H. & Artis, D. Neuro-immune crosstalk and allergic inflammation. J. Clin. Invest. 129, 1475–1482 (2019).
pubmed: 30829650
pmcid: 6436850
Ohanyan, T. et al. Role of substance P and its receptor neurokinin 1 in chronic prurigo: a randomized, proof-of-concept, controlled trial with topical aprepitant. Acta Derm. Venereol. 98, 26–31 (2018).
pubmed: 28853492
Nakashima, C., Ishida, Y., Kitoh, A., Otsuka, A. & Kabashima, K. Interaction of peripheral nerves and mast cells, eosinophils, and basophils in the development of pruritus. Exp. Dermatol. 28, 1405–1411 (2019).
pubmed: 31365150
Konstantinou, G. N., Gerasimos, N. K., Koulias, C., Petalas, K. & Makris, M. Further understanding of neuro-immune interactions in allergy: implications in pathophysiology and role in disease progression. J. Asthma Allergy 15, 1273–1291 (2022).
pubmed: 36117919
pmcid: 9473548
Coffey, C. S., Mulligan, R. M. & Schlosser, R. J. Mucosal expression of nerve growth factor and brain-derived neurotrophic factor in chronic rhinosinusitis. Am. J. Rhinol. Allergy 23, 571–574 (2009).
pubmed: 19958603
Renert-Yuval, Y. et al. Biomarkers in atopic dermatitis — a review on behalf of the International Eczema Council. J. Allergy Clin. Immunol. 147, 1174–11901 (2021).
pubmed: 33516871
Matsuo, K. et al. CCR4 is critically involved in skin allergic inflammation of BALB/c mice. J. Invest. Dermatol. 138, 1764–1773 (2018).
pubmed: 29510192
Perros, F., Hoogsteden, H. C., Coyle, A. J., Lambrecht, B. N. & Hammad, H. Blockade of CCR4 in a humanized model of asthma reveals a critical role for DC-derived CCL17 and CCL22 in attracting T
pubmed: 19630858
Liu, Y. J. Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell-mediated allergic inflammation. J. Allergy Clin. Immunol. 120, 238–244 (2007); quiz 245–236.
pubmed: 17666213
Salek-Ardakani, S. et al. OX40 (CD134) controls memory T helper 2 cells that drive lung inflammation. J. Exp. Med. 198, 315–324 (2003).
pubmed: 12860930
pmcid: 2194076
Seshasayee, D. et al. In vivo blockade of OX40 ligand inhibits thymic stromal lymphopoietin driven atopic inflammation. J. Clin. Invest. 117, 3868–3878 (2007).
pubmed: 18060034
pmcid: 2096422
Menzies-Gow, A. et al. Tezepelumab in adults and adolescents with severe, uncontrolled asthma. N. Engl. J. Med. 384, 1800–1809 (2021).
pubmed: 33979488
Corren, J. et al. Tezepelumab in adults with uncontrolled asthma. N. Engl. J. Med. 377, 936–946 (2017). This publication reports the results of a clinical trial of tezepelumab in asthma including decreased rates of exacerbations in patients with asthma independently of type 2 markers.
pubmed: 28877011
Corren, J. et al. Effects of combination treatment with tezepelumab and allergen immunotherapy on nasal responses to allergen: a randomized controlled trial. J. Allergy Clin. Immunol. 151, 192–201 (2023).
pubmed: 36223848
Simpson, E. L. et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: a randomized phase 2a clinical trial. J. Am. Acad. Dermatol. 80, 1013–1021 (2019).
pubmed: 30550828
Wechsler, M. E. et al. Efficacy and safety of itepekimab in patients with moderate-to-severe asthma. N. Engl. J. Med. 385, 1656–1668 (2021).
pubmed: 34706171
Kelsen, S. G. et al. Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: a randomized clinical trial. J. Allergy Clin. Immunol. 148, 790–798 (2021).
pubmed: 33872652
Chen, Y. L. et al. Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis. Sci. Transl. Med. 11, eaax2945 (2019).
pubmed: 31645451
Maurer, M. et al. Phase 2 randomized clinical trial of astegolimab in patients with moderate to severe atopic dermatitis. J. Allergy Clin. Immunol. 150, 1517–1524 (2022).
pubmed: 36041655
Silverberg, J. I. et al. Dupilumab treatment results in early and sustained improvements in itch in adolescents and adults with moderate to severe atopic dermatitis: analysis of the randomized phase 3 studies SOLO 1 and SOLO 2, AD ADOL, and CHRONOS. J. Am. Acad. Dermatol. 82, 1328–1336 (2020).
pubmed: 32135208
Castro, M. et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N. Engl. J. Med. 378, 2486–2496 (2018).
pubmed: 29782217
Rabe, K. F. et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N. Engl. J. Med. 378, 2475–2485 (2018).
pubmed: 29782224
Bachert, C. et al. Efficacy and safety of dupilumab in patients with severe chronic rhinosinusitis with nasal polyps (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52): results from two multicentre, randomised, double-blind, placebo-controlled, parallel-group phase 3 trials. Lancet 394, 1638–1650 (2019).
pubmed: 31543428
Yosipovitch, G. et al. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nat. Med. 29, 1180–1190 (2023). This publication reports the results of the phase III trials of dupilumab in adult patients with CPG showing significant improvements in itch and skin lesions.
pubmed: 37142763
pmcid: 10202800
Lee, S. J., Kim, S. E., Shin, K. O., Park, K. & Lee, S. E. Dupilumab therapy improves stratum corneum hydration and skin dysbiosis in patients with atopic dermatitis. Allergy Asthma Immunol. Res. 13, 762–775 (2021).
pubmed: 34486260
pmcid: 8419647
Guttman-Yassky, E. et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J. Allergy Clin. Immunol. 143, 155–172 (2019).
pubmed: 30194992
Paller, A. S. et al. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 400, 908–919 (2022). This paper demonstrates dupilumab efficacy and safety in children aged <6 years with AD.
pubmed: 36116481
Hoshino, M., Akitsu, K., Kubota, K. & Ohtawa, J. Efficacy of a house dust mite sublingual immunotherapy tablet as add-on dupilumab in asthma with rhinitis. Allergol. Int. 71, 490–497 (2022).
pubmed: 35718711
Peters, A. T. et al. Indirect treatment comparison of biologics in chronic rhinosinusitis with nasal polyps. J. Allergy Clin. Immunol. Pract. 9, 2461–24715 (2021).
pubmed: 33548517
Oykhman, P. et al. Comparative efficacy and safety of monoclonal antibodies and aspirin desensitization for chronic rhinosinusitis with nasal polyposis: a systematic review and network meta-analysis. J. Allergy Clin. Immunol. 149, 1286–1295 (2022).
pubmed: 34543652
Boechat, J. L., Silva, D., Sousa-Pinto, B. & Delgado, L. Comparing biologicals for severe chronic rhinosinusitis with nasal polyps: a network meta-analysis. Allergy 77, 1299–1306 (2022).
pubmed: 34981835
Maurer, M. et al. Dupilumab significantly reduces itch and hives in patients with chronic spontaneous urticaria: results from a phase 3 trial (LIBERTY-CSU CUPID Study A). J. Allergy Clin. Immunol. 149, AB312 (2022).
Sirufo, M. M. et al. Cholinergic urticaria, an effective and safe “off label” use of dupilumab: a case report with literature review. Clin. Cosmet. Investig. Dermatol. 15, 253–260 (2022).
pubmed: 35210803
pmcid: 8863185
Goodman, B. & Jariwala, S. Dupilumab as a novel therapy to treat adrenergic urticaria. Ann. Allergy Asthma Immunol. 126, 205–206 (2021).
pubmed: 32621993
Ferrucci, S., Benzecry, V., Berti, E. & Asero, R. Rapid disappearance of both severe atopic dermatitis and cold urticaria following dupilumab treatment. Clin. Exp. Dermatol. 45, 345–346 (2020).
pubmed: 31437869
Key Med Biosciences. Primary study endpoints from phase III clinical trial of CM310 for the treatment of moderate to severe atopic dermatitis in adults. Key Med Biosciences. https://en.keymedbio.com/show-132-194-1.html (2023).
Strober, B. et al. Efficacy and safety of CBP-201 in adults with moderate-to-severe atopic dermatitis (AD): a phase 2b, randomized, double-blind, placebo-controlled trial (CBP-201-WW001). Presented at Maui Derm Conference. https://www.connectbiopharm.com/wp-content/uploads/Maui-derm-2022_CBP-201_Poster-1_FINAL_10th-January-2022.pdf (2022).
AkesoBio. IL-4Rα monoclonal antibody (AK120) initiates a global phase II clinical trial for the treatment of moderate-to-severe atopic dermatitis. AkesoBio. https://www.akesobio.com/en/media/akeso-news/210927/ (2021).
Silverberg, J. I. et al. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br. J. Dermatol. 184, 450–463 (2021).
pubmed: 33000503
pmcid: 7986183
Beck, L. A. et al. Tralokinumab treatment improves the skin microbiota by increasing the microbial diversity in adults with moderate-to-severe atopic dermatitis: analysis of microbial diversity in ECZTRA 1, a randomized controlled trial. J. Am. Acad. Dermatol. 88, 816–823 (2023).
pubmed: 36473633
Stolzl, D., Weidinger, S. & Drerup, K. A new era has begun: treatment of atopic dermatitis with biologics. Allergol. Sel. 5, 265–273 (2021).
Eli Lilly. Majority of patients treated with lebrikizumab achieved skin clearance in Lilly’s pivotal phase 3 atopic dermatitis studies. Lilly https://investor.lilly.com/news-releases/news-release-details/majority-patients-treated-lebrikizumab-achieved-skin-clearance (2022).
Eli Lilly. Lebrikizumab dosed every four weeks maintained durable skin clearance in Lilly’s phase 3 monotherapy atopic dermatitis trials. Lilly. https://investor.lilly.com/news-releases/news-release-details/lebrikizumab-dosed-every-four-weeks-maintained-durable-skin (2022).
Dellon, E. S. et al. Long-term efficacy and tolerability of RPC4046 in an open-label extension trial of patients with eosinophilic esophagitis. Clin. Gastroenterol. Hepatol. 19, 473–483.e17 (2021).
pubmed: 32205221
Lucendo, A. J. & López-Sánchez, P. Targeted therapies for eosinophilic gastrointestinal disorders. BioDrugs 34, 477–493 (2020).
pubmed: 32472465
Blauvelt, A. Eblasakimab, a human IL-13 Rα1 monoclonal antibody, in adult patients with moderate-to-severe dermatitis: a randomized double-blind, placebo-controlled proof-of-concept study. In American Academy of Dermatology Annual Meeting, Boston, MA, USA, 26 March 2022 Oral presentation at session S026 (AAD. 2022).
Hanania, N. A. et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials. Lancet Respir. Med. 4, 781–796 (2016).
pubmed: 27616196
Panettieri, J. et al. Tralokinumab for severe, uncontrolled asthma (STRATOS 1 and STRATOS 2): two randomised, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir. Med. 6, 511–525 (2018).
pubmed: 29792288
Pavord, I. D. et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet 380, 651–659 (2012).
pubmed: 22901886
Ortega, H. G. et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N. Engl. J. Med. 371, 1198–1207 (2014).
pubmed: 25199059
Bachert, C. et al. Mepolizumab improves quality of life and reduces activity impairments in patients with CRSwNP. Rhinology 60, 474–478 (2022).
pubmed: 36436220
Castro, M. et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir. Med. 3, 355–366 (2015).
pubmed: 25736990
Bachert, C. et al. Reduced need for surgery in severe nasal polyposis with mepolizumab: randomized trial. J. Allergy Clin. Immunol. 140, 1024–1031.e14 (2017).
pubmed: 28687232
Han, J. K. et al. Mepolizumab for chronic rhinosinusitis with nasal polyps (SYNAPSE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir. Med. 9, 1141–1153 (2021).
pubmed: 33872587
Magerl, M. et al. Benefit of mepolizumab treatment in a patient with chronic spontaneous urticaria. J. Dtsch. Dermatol. Ges. 16, 477–478 (2018).
pubmed: 29578281
Antonicelli, L., Tontini, C., Garritani, M. S., Piga, M. A. & Bilò, M. B. Efficacy of mepolizumab in patients with concomitant severe eosinophilic asthma and severe chronic urticaria: an example of personalized medicine? J. Investig. Allergol. Clin. Immunol. 33, 54–56 (2023).
pubmed: 34842174
Maurer, M. et al. Benefit from reslizumab treatment in a patient with chronic spontaneous urticaria and cold urticaria. J. Eur. Acad. Dermatol. Venereol. 32, 112–113 (2018).
Gevaert, P. et al. Nasal IL-5 levels determine the response to anti-IL-5 treatment in patients with nasal polyps. J. Allergy Clin. Immunol. 118, 1133–1141 (2006).
pubmed: 17088140
Oldhoff, J. M. et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy 60, 693–696 (2005).
pubmed: 15813818
Bleecker, E. R. et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet 388, 2115–2127 (2016).
pubmed: 27609408
FitzGerald, J. M. et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 388, 2128–2141 (2016).
pubmed: 27609406
Nair, P. et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N. Engl. J. Med. 376, 2448–2458 (2017).
pubmed: 28530840
Bernstein, J. A. et al. Benralizumab for chronic spontaneous urticaria. N. Engl. J. Med. 383, 1389–1391 (2020).
pubmed: 32997916
Bernstein, J. A. et al. Treatment of chronic spontaneous urticaria with benralizumab: report of primary endpoint per-protocol analysis and exploratory endpoints. Allergy 76, 1277–1280 (2021).
pubmed: 33326617
Bergmann, K. C., Altrichter, S. & Maurer, M. Benefit of benralizumab treatment in a patient with chronic symptomatic dermographism. J. Eur. Acad. Dermatol. Venereol. 33, 413–415 (2019).
Bachert, C. et al. Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps: a randomized, placebo-controlled trial. J. Allergy Clin. Immunol. 149, 1309–1317.e12 (2022).
pubmed: 34599979
Schwartz, D. M. et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat. Rev. Drug Discov. 17, 78 (2017).
pubmed: 29282366
pmcid: 6168198
He, H. & Guttman-Yassky, E. JAK inhibitors for atopic dermatitis: an update. Am. J. Clin. Dermatol. 20, 181–192 (2019).
pubmed: 30536048
Bieber, T. et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. N. Engl. J. Med. 384, 1101–1112 (2021).
pubmed: 33761207
Stölzl, D. et al. Real-world data on the effectiveness, safety and drug survival of dupilumab: an analysis from the TREATgermany registry. Br. J. Dermatol. 187, 1022–1024 (2022).
pubmed: 35895855
Simpson, E. L. et al. Efficacy and safety of upadacitinib in patients with moderate to severe atopic dermatitis: analysis of follow-up data from the Measure Up 1 and Measure Up 2 randomized clinical trials. JAMA Dermatol. 158, 404–413 (2022).
pubmed: 35262646
pmcid: 8908226
Simpson, E. L. et al. Safety of tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled phase II and phase III trials. Br. J. Dermatol. 187, 888–899 (2022).
pubmed: 36082590
pmcid: 10091996
Reich, K. et al. Efficacy and safety of abrocitinib versus dupilumab in adults with moderate-to-severe atopic dermatitis: a randomised, double-blind, multicentre phase 3 trial. Lancet 400, 273–282 (2022).
pubmed: 35871814
Guttman-Yassky, E. et al. Safety of upadacitinib in moderate-to-severe atopic dermatitis: an integrated analysis of phase 3 studies. J. Allergy Clin. Immunol. 151, 172–181 (2023).
pubmed: 36195170
Reich, K. et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 397, 2169–2181 (2021).
pubmed: 34023009
Silverberg, J. I. et al. Comparative efficacy of targeted systemic therapies for moderate to severe atopic dermatitis without topical corticosteroids: systematic review and network meta-analysis. Dermatol. Ther. 12, 1181–1196 (2022).
Papp, K. et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies. J. Am. Acad. Dermatol. 85, 863–872 (2021).
pubmed: 33957195
Nakagawa, H. et al. Phase 2 clinical study of delgocitinib ointment in pediatric patients with atopic dermatitis. J. Allergy Clin. Immunol. 144, 1575–1583 (2019).
pubmed: 31425780
Piscitelli, S. C. et al. A phase 1b, randomized, single-center trial of topical cerdulatinib (DMVT-502) in patients with mild-to-moderate atopic dermatitis. J. Invest. Dermatol. 141, 1847–1851 (2021).
pubmed: 33493530
Bonnekoh, H., Butze, M. & Metz, M. Characterization of the effects on pruritus by novel treatments for atopic dermatitis. J. Dtsch. Dermatol. Ges. 20, 150–156 (2022).
pubmed: 35146882
He, Y., Ji, S. & Yu, Q. Effectiveness of baricitinib in prurigo-type atopic dermatitis: a case report. Dermatol. Ther. 34, e14878 (2021).
pubmed: 33583117
Pereira, M. P., Zeidler, C. & Stander, S. Improvement of chronic nodular prurigo with baricitinib. J. Eur. Acad. Dermatol. Venereol. 36, e486–e488 (2022).
pubmed: 35138657
Yin, M., Wu, R., Chen, J. & Dou, X. Successful treatment of refractory prurigo nodularis with baricitinib. Dermatol. Ther. 35, e15642 (2022).
pubmed: 35708292
Mansouri, P., Mozafari, N., Chalangari, R. & Martits-Chalangari, K. Efficacy of oral tofacitinib in refractory chronic spontaneous urticaria and urticarial vasculitis. Dermatol. Ther. 35, e15932 (2022).
pubmed: 36226796
Fukunaga, A., Ito, M. & Nishigori, C. Efficacy of oral ruxolitinib in a patient with refractory chronic spontaneous urticaria. Acta Derm. Venereol. 98, 904–905 (2018).
pubmed: 29978888
Agache, I. et al. EAACI Biologicals Guidelines — omalizumab for the treatment of chronic spontaneous urticaria in adults and in the paediatric population 12–17 years old. Allergy 77, 17–38 (2022).
pubmed: 34324716
Wedi, B. & Traidl, S. Anti-IgE for the treatment of chronic urticaria. Immunotargets Ther. 10, 27–45 (2021).
pubmed: 33628747
pmcid: 7898214
Gevaert, P. et al. Efficacy and safety of omalizumab in nasal polyposis: 2 randomized phase 3 trials. J. Allergy Clin. Immunol. 146, 595–605 (2020).
pubmed: 32524991
Lopez-Abente, J. et al. Omalizumab restores the ability of human plasmacytoid dendritic cells to induce Foxp3
pubmed: 32675208
Benito-Villalvilla, C. et al. Ligelizumab impairs IgE-binding to plasmacytoid dendritic cells more potently than omalizumab and restores IFN-α production and FOXP3
pubmed: 36315052
Palomares, O., Elewaut, D., Irving, P. M., Jaumont, X. & Tassinari, P. Regulatory T cells and immunoglobulin E: a new therapeutic link for autoimmunity? Allergy 77, 3293–3308 (2022).
pubmed: 35852798
De Filippo, M. et al. Omalizumab and allergen immunotherapy for respiratory allergies: a mini-review from the Allergen-Immunotherapy Committee of the Italian Society of Pediatric Allergy and Immunology (SIAIP). Allergol. Immunopathol. 50, 47–52 (2022).
Malipiero, G. et al. Allergen immunotherapy and biologics in respiratory allergy: friends or foes? Curr. Opin. Allergy Clin. Immunol. 21, 16–23 (2021).
pubmed: 33369567
Chan, S., Cornelius, V., Cro, S., Harper, J. I. & Lack, G. Treatment effect of omalizumab on severe pediatric atopic dermatitis: the ADAPT randomized clinical trial. JAMA Pediatr. 174, 29–37 (2020).
pubmed: 31764962
Maurer, M. et al. Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria. N. Engl. J. Med. 368, 924–935 (2013). This work is a key study of efficacy of omalizumab in CSU.
pubmed: 23432142
Gasser, P. et al. The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab. Nat. Commun. 11, 165 (2020).
pubmed: 31913280
pmcid: 6949303
Maurer, M. et al. Ligelizumab for chronic spontaneous urticaria. N. Engl. J. Med. 381, 1321–1332 (2019).
pubmed: 31577874
Novartis. Novartis provides an update on phase III ligelizumab (QGE031) studies in chronic spontaneous urticaria (CSU). Novartis. https://www.novartis.com/news/media-releases/novartis-provides-update-phase-iii-ligelizumab-qge031-studies-chronic-spontaneous-urticaria-csu (2021).
Trischler, J. et al. Ligelizumab treatment for severe asthma: learnings from the clinical development programme. Clin. Transl. Immunol. 10, e1255 (2021).
Liour, S. S., Tom, A., Chan, Y.-H. & Chang, T. W. Treating IgE-mediated diseases via targeting IgE-expressing B cells using an anti-CεmX antibody. Pediatr. Allergy Immunol. 27, 446–451 (2016).
pubmed: 27090058
Kuo, B.-S. et al. IgE-neutralizing UB-221 mAb, distinct from omalizumab and ligelizumab, exhibits CD23-mediated IgE downregulation and relieves urticaria symptoms. J. Clin. Invest. 132, e157765 (2022).
pubmed: 35912861
pmcid: 9337824
Metz, M. et al. Fenebrutinib in H
pubmed: 34750553
pmcid: 8604722
Maurer, M. et al. Remibrutinib, a novel BTK inhibitor, demonstrates promising efficacy and safety in chronic spontaneous urticaria. J. Allergy Clin. Immunol. 150, 1498–1506.e92 (2022).
pubmed: 36096203
Kaul, M. et al. Remibrutinib (LOU064): a selective potent oral BTK inhibitor with promising clinical safety and pharmacodynamics in a randomized phase I trial. Clin. Transl. Sci. 14, 1756–1768 (2021).
pubmed: 33834628
pmcid: 8504815
Rymut, S. M. et al. Dose-dependent inactivation of airway tryptase with a novel dissociating anti-tryptase antibody (MTPS9579A) in healthy participants: a randomized trial. Clin. Transl. Sci. 15, 451–463 (2022).
pubmed: 34581002
Oliver, E. T. et al. Effects of an oral CRTh2 antagonist (AZD1981) on eosinophil activity and symptoms in chronic spontaneous urticaria. Int. Arch. Allergy Immunol. 179, 21–30 (2019).
pubmed: 30879003
Castro, M. et al. Efficacy and safety of fevipiprant in patients with uncontrolled asthma: two replicate, phase 3, randomised, double-blind, placebo-controlled trials (ZEAL-1 and ZEAL-2). eClinicalMedicine 35, 100847 (2021).
pubmed: 33997741
pmcid: 8099656
Asano, K. et al. A phase 2a study of DP2 antagonist GB001 for asthma. J. Allergy Clin. Immunol. Pract. 8, 1275–12831 (2020).
pubmed: 31778823
Altrichter, S. et al. An open-label, proof-of-concept study of lirentelimab for antihistamine-resistant chronic spontaneous and inducible urticaria. J. Allergy Clin. Immunol. 149, 1683–1690 (2022). This work presents a proof-of-concept study of mast cell sliencing with the anti-Siglec-8 antibody lirentelimab, in CSU and CIndU.
pubmed: 34954198
Terhorst-Molawi, D. et al. Anti-KIT antibody, barzolvolimab, reduces skin mast cells and disease activity in chronic inducible urticaria. Allergy 78, 1269–1279 (2022). This work presents the first study showing efficacy of mast cell depletion with the anti-KIT monoclonal antibody barzolvolimab in CIndU.
pubmed: 36385701
Bernstein, J. et al. Effects of multiple dose treatment with an anti-KIT antibody, CDX-0159, in chronic spontaneous urticaria [abstract 100097]. Allergy 78, 416 (2023).
Davidescu, L. et al. Efficacy and safety of masitinib in corticosteroid-dependent severe asthma: a randomized placebo-controlled trial. J. Asthma Allergy 15, 737–747 (2022).
pubmed: 35698580
pmcid: 9188333
Silverberg, J. I. et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J. Allergy Clin. Immunol. 145, 173–182 (2020).
pubmed: 31449914
Ruzicka, T. et al. Anti-interleukin-31 receptor a antibody for atopic dermatitis. N. Engl. J. Med. 376, 826–835 (2017).
pubmed: 28249150
Kabashima, K., Matsumura, T., Komazaki, H., Kawashima, M. & Nemolizumab, J. P. S. G. Trial of nemolizumab and topical agents for atopic dermatitis with pruritus. N. Engl. J. Med. 383, 141–150 (2020).
pubmed: 32640132
Galderma. Galderma delivers strong FY 2022 growth driven by innovation and commercial performance. Galderma. https://www.galderma.com/news/galderma-delivers-strong-fy-2022-growth-driven-innovation-and-commercial-performance (2023).
Ständer, S. et al. Trial of nemolizumab in moderate-to-severe prurigo nodularis. N. Engl. J. Med. 382, 706–716 (2020).
pubmed: 32074418
Ständer, S. et al. Nemolizumab efficacy in prurigo nodularis: onset of action on itch and sleep disturbances. J. Eur. Acad. Dermatol. Venereol. 36, 1820–1825 (2022).
pubmed: 35766128
pmcid: 9796585
Galderma. AAD 2023: late-breaking phase III results demonstrate nemolizumab’s significant impact on prurigo nodularis. Galderma. https://www.galderma.com/news/aad-2023-late-breaking-phase-iii-results-demonstrate-nemolizumabs-significant-impact-prurigo-1 (2023).
Sofen, H. et al. Efficacy and safety of vixarelimab, a human monoclonal oncostatin M receptor β antibody, in moderate-to-severe prurigo nodularis: a randomised, double-blind, placebo-controlled, phase 2a study. eClinicalMedicine 57, 101826 (2023).
pubmed: 36816342
pmcid: 9932343
Mikhak, Z. et al. KPL-716, anti-oncostatin M receptor β antibody, reduced pruritus in atopic dermatitis [abstract 560]. J. Invest. Dermatol. 139, S96 (2019).
Ständer, S. et al. Serlopitant reduced pruritus in patients with prurigo nodularis in a phase 2, randomized, placebo-controlled trial. J. Am. Acad. Dermatol. 80, 1395–1402 (2019).
pubmed: 30894279
Ogasawara, H., Furuno, M., Edamura, K. & Noguchi, M. Novel MRGPRX2 antagonists inhibit IgE-independent activation of human umbilical cord blood-derived mast cells. J. Leukoc. Biol. 106, 1069–1077 (2019).
pubmed: 31299111
Guttman-Yassky, E. et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J. Allergy Clin. Immunol. 144, 482–493.e7 (2019).
pubmed: 30738171
Nakagawa, H. et al. Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis. J. Dermatol. Sci. 99, 82–89 (2020).
pubmed: 32651105
Saghari, M. et al. OX40L inhibition suppresses KLH-driven immune responses in healthy volunteers: a randomized controlled trial demonstrating proof-of-pharmacology for KY1005. Clin. Pharmacol. Ther. 111, 1121–1132 (2022).
pubmed: 35092305
pmcid: 9314635
Sher, L. et al. 472 Telazorlimab in atopic dermatitis: phase 2b study shows improvement at 16 weeks. J. Invest. Dermatol. 141, S82 (2021).
Guttman-Yassky, E. et al. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study. Lancet 401, 204–214 (2023). The results of this phase IIb study show progressive improvements in AD maintained in most patients even after discontinuation of treatment with rocatinlimab.
pubmed: 36509097
Sanofi. New, late-breaking data at EADV highlights emerging clinical profile of amlitelimab (formerly KY1005) in adults with inadequately controlled moderate-to-severe atopic dermatitis. Sanofi. https://www.sanofi.com/en/media-room/press-releases/2021/2021-09-30-12-30-00-2306183 (2021).
Laulajainen-Hongisto, A. et al. Genomics of asthma, allergy and chronic rhinosinusitis: novel concepts and relevance in airway mucosa. Clin. Transl. Allergy 10, 45 (2020).
pubmed: 33133517
pmcid: 7592594
Holloway, J. W., Yang, I. A. & Holgate, S. T. Genetics of allergic disease. J. Allergy Clin. Immunol. 125 (Suppl. 2), S81–S94 (2010).
pubmed: 20176270
Bellinghausen, I., Khatri, R. & Saloga, J. Current strategies to modulate regulatory T cell activity in allergic inflammation. Front. Immunol. 13, 912529S (2022).
Godar, M. et al. A bispecific antibody strategy to target multiple type 2 cytokines in asthma. J. Allergy Clin. Immunol. 142, 1185 (2018).
pubmed: 29890236
pmcid: 7610797
Barnes, P. J. Role of GATA-3 in allergic diseases. Curr. Mol. Med. 8, 330–334 (2008).
pubmed: 18691059
Potaczek, D. P., Garn, H., Unger, S. D. & Renz, H. Antisense molecules: a new class of drugs. J. Allergy Clin. Immunol. 137, 1334–1346 (2016).
pubmed: 27155029
Krug, N. et al. Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme. N. Engl. J. Med. 372, 1987–1995 (2015). This report evaluates the safety and efficacy of SB010, a novel DNAzyme targeted against GATA3 mRNA in patients with allergic asthma.
pubmed: 25981191
Jansson, Å. et al. Efficient anti-IgE vaccination without anaphylactogenic properties. J. Allergy Clin. Immunol. 113, S254 (2004).
Conde, E. et al. Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice. Nat. Commun. 12, 2574 (2021).
pubmed: 33976140
pmcid: 8113315
Chen, S. et al. Treatment of allergic eosinophilic asthma through engineered IL-5-anchored chimeric antigen receptor T cells. Cell Discov. 8, 80 (2022).
pubmed: 35973984
pmcid: 9381771
Nettis, E. et al. Effectiveness and safety of dupilumab in patients with chronic rhinosinusitis with nasal polyps and associated comorbidities: a multicentric prospective study in real life. Clin. Mol. Allergy 20, 6 (2022).
pubmed: 35590407
pmcid: 9121619
Nnane, I. et al. The first-in-human study of CNTO 7160, an anti-interleukin-33 receptor monoclonal antibody, in healthy subjects and patients with asthma or atopic dermatitis. Br. J. Clin. Pharmacol. 86, 2507–2518 (2020).
pubmed: 32415720
pmcid: 7688540
Simpson, E. L. et al. Efficacy and safety of lebrikizumab in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis: a randomized clinical trial (ADhere). JAMA Dermatol. 159, 182–191 (2023).
pubmed: 36630140
pmcid: 9857439
Silverberg, J. I. et al. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N. Engl. J. Med. 388, 1080–1091 (2023). This publication describes the results of two phase III trials of lebrikizumab efficacy in adolescents and adults with moderate to severe AD.
pubmed: 36920778
Whetstone, C. et al. Effect of benralizumab on skin responses to intradermal allergen challenge in patients with moderate-to-severe atopic dermatitis. J. Allergy Clin. Immunol. 149, AB322 (2022).
Zhao, Y. et al. Efficacy and safety of SHR0302, a highly selective Janus kinase 1 inhibitor, in patients with moderate to severe atopic dermatitis: a phase II randomized clinical trial. Am. J. Clin. Dermatol. 22, 877–889 (2021).
pubmed: 34374027
pmcid: 8351769
Landis, M. N. et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle-controlled, dose-ranging and parallel-group study. Br. J. Dermatol. 187, 878–887 (2022).
pubmed: 35986699
pmcid: 10092158
Weidinger, S. et al. 33781 Sustained and durable response up to 24 weeks after last dose observed in a phase 2a study (NCT03754309) of amlitelimab (KY1005, SAR445229) a novel nondepleting anti-OX40Ligand (OX40L) mAb in patients with moderate to severe atopic dermatitis (AD). J. Am. Acad. Dermatol. 87, AB206 (2022).
Maurer, M. et al. Sustained safety and efficacy of ligelizumab in patients with chronic spontaneous urticaria: a one-year extension study. Allergy 77, 2175–2184 (2022).
pubmed: 34773261
Dickson, M. C. et al. Effects of a topical treatment with spleen tyrosine kinase inhibitor in healthy subjects and patients with cold urticaria or chronic spontaneous urticaria: results of a phase 1a/b randomised double-blind placebo-controlled study. Br. J. Clin. Pharmacol. 87, 4797–4808 (2021).
pubmed: 34020509
Shinkai, M. et al. One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study. J. Asthma 60, 616–624 (2023).
pubmed: 35707873
Wechsler, M. E. et al. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): a randomised, placebo-controlled, phase 3 study. Lancet Resp. Med. 10, 650–660 (2022).
Menzies-Gow, A. et al. Long-term safety and efficacy of tezepelumab in people with severe, uncontrolled asthma (DESTINATION): a randomised, placebo-controlled extension study. Lancet Respir. Med. 11, 425–438 (2023).
pubmed: 36702146
Gauvreau, G. M. et al. Inhaled anti-TSLP antibody fragment, ecleralimab, blocks responses to allergen in mild asthma. Eur. Respir. J. 61, 2201193 (2023).
pubmed: 36822634
pmcid: 9996823
Maintz, L., Bieber, T., Simpson, H. D. & Demessant-Flavigny, A. L. From skin barrier dysfunction to systemic impact of atopic dermatitis: implications for a precision approach in dermocosmetics and medicine. J. Pers. Med. 12, 893 (2022).
pubmed: 35743678
pmcid: 9225544
Hox, V. et al. Benefits and harm of systemic steroids for short- and long-term use in rhinitis and rhinosinusitis: an EAACI position paper. Clin. Transl. Allergy 10, 1 (2020).
pubmed: 31908763
pmcid: 6941282
Alsharif, S. et al. Endoscopic sinus surgery for type-2 CRS wNP: an endotype-based retrospective study. Laryngoscope 129, 1286–1292 (2019).
pubmed: 30663058
Gevaert, P. et al. Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma. J. Allergy Clin. Immunol. 131, 110–116.e1 (2013).
pubmed: 23021878
Gevaert, P. et al. Long-term efficacy and safety of omalizumab for nasal polyposis in an open-label extension study. J. Allergy Clin. Immunol. 149, 957–965.e3 (2022).
pubmed: 34530020
Gevaert, P. et al. Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis. J. Allergy Clin. Immunol. 128, 989–995.e1–e8 (2011).
pubmed: 21958585
Bachert, C. et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. J. Am. Med. Assoc. 315, 469–479 (2016). This paper reports the efficacy of dupilumab in adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids.
Yew, Y. W., Thyssen, J. P. & Silverberg, J. I. A systematic review and meta-analysis of the regional and age-related differences in atopic dermatitis clinical characteristics. J. Am. Acad. Dermatol. 80, 390–401 (2019).
pubmed: 30287309
Boozalis, E. et al. Ethnic differences and comorbidities of 909 prurigo nodularis patients. J. Am. Acad. Dermatol. 79, 714–719.e3 (2018).
pubmed: 29733939
pmcid: 6518410
Huang, A. H., Canner, J. K., Khanna, R., Kang, S. & Kwatra, S. G. Real-world prevalence of prurigo nodularis and burden of associated diseases. J. Invest. Dermatol. 140, 480–483.e4 (2020).
pubmed: 31421126
De Bruin-Weller, M. et al. Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies. Acta Derm. Venereol. 101, adv00402 (2021).
pubmed: 33491094
Porsbjerg, C., Melén, E., Lehtimäki, L. & Shaw, D. Asthma. Lancet 401, 858–873 (2023).
pubmed: 36682372
Galli, S. J. Toward precision medicine and health: opportunities and challenges in allergic diseases. J. Allergy Clin. Immunol. 137, 1289 (2016).
pubmed: 27155026
pmcid: 4872702
Asero, R. et al. Co-occurrence of IgE and IgG autoantibodies in patients with chronic spontaneous urticaria. Clin. Exp. Immunol. 200, 242–249 (2020).
pubmed: 32115683
pmcid: 7231996
Farzan, N., Vijverberg, S. J. H., Arets, H. G., Raaijmakers, J. A. M. & Maitland-van der Zee, A. H. Pharmacogenomics of inhaled corticosteroids and leukotriene modifiers: a systematic review. Clin. Exp. Allergy 47, 271–293 (2017).
pubmed: 27790783
Agache, I. & Akdis, C. A. Precision medicine and phenotypes, endotypes, genotypes, regiotypes, and theratypes allergic diseases. J. Clin. Invest. 129, 1493–1503 (2019). This publication scrutinizes and discusses a precision medicine approach that stratifies patients based on disease mechanisms to optimize management of allergic diseases.
pubmed: 30855278
pmcid: 6436902
Settipane, R. A., Kreindler, J. L., Chung, Y. & Tkacz, J. Evaluating direct costs and productivity losses of patients with asthma receiving GINA 4/5 therapy in the United States. Ann. Allergy Asthma Immunol. 123, 564–572.e3 (2019).
pubmed: 31494235
Pereira, M. P. et al. Chronic nodular prurigo: a European cross-sectional study of patient perspectives on therapeutic goals and satisfaction. Acta Derm. Venereol. 101, adv00403 (2021).
pubmed: 33320272
Guillen-Aguinaga, S., Jauregui Presa, I., Aguinaga-Ontoso, E., Guillen-Grima, F. & Ferrer, M. Updosing nonsedating antihistamines in patients with chronic spontaneous urticaria: a systematic review and meta-analysis. Br. J. Dermatol. 175, 1153–1165 (2016).
pubmed: 27237730
Tharp, M. D. et al. Benefits and harms of omalizumab treatment in adolescent and adult patients with chronic idiopathic (spontaneous) urticaria: a meta-analysis of “real-world” evidence. JAMA Dermatol. 155, 29–38 (2019).
pubmed: 30427977
Maurer, M. et al. Unmet clinical needs in chronic spontaneous urticaria. A GA²LEN task force report. Allergy 66, 317–330 (2011).
pubmed: 21083565
Alves, F., Calado, R., Relvas, M., Gomes, T. & Gonçalo, M. Short courses of ciclosporin can induce long remissions in chronic spontaneous urticaria. J. Eur. Acad. Dermatol. Venereol. 36, 645–646 (2022).
Maurer, M. et al. Efficacy and safety of omalizumab in patients with chronic urticaria who exhibit IgE against thyroperoxidase. J. Allergy Clin. Immunol. 128, 202–209.e5 (2011).
pubmed: 21636116
Kolkhir, P. et al. The benefit of complete response to treatment in patients with chronic spontaneous urticaria — CURE results. J. Allergy Clin. Immunol. Pract. 11, 610–620.e5 (2023).
pubmed: 36481420
Lommatzsch, M. et al. Disease-modifying anti-asthmatic drugs. Lancet 399, 1664–1668 (2022).
pubmed: 35461560
Wangberg, H. & Woessner, K. Choice of biologics in asthma endotypes. Curr. Opin. Allergy Clin. Immunol. 21, 79–85 (2021).
pubmed: 33306486
Manka, L. A. & Wechsler, M. E. Selecting the right biologic for your patients with severe asthma. Ann. Allergy Asthma Immunol. 121, 406–413 (2018).
pubmed: 30056149
Jackson, D. J. et al. Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era. Thorax 76, 220–227 (2021).
pubmed: 33298582
Pfaller, B. et al. Biologicals in atopic disease in pregnancy: an EAACI position paper. Allergy 76, 71–89 (2021).
pubmed: 32189356
Middleton, P. G. et al. ERS/TSANZ Task Force Statement on the management of reproduction and pregnancy in women with airways diseases. Eur. Respir. J. 55, 1901208 (2020).
pubmed: 31699837
Samedy-Bates, L.-A. et al. Racial/ethnic-specific differences in the effects of inhaled corticosteroid use on bronchodilator response in patients with asthma. Clin. Pharmacol. Ther. 106, 1133–1140 (2019).
pubmed: 31209858
Oh, S. S., White, M. J., Gignoux, C. R. & Burchard, E. G. Making precision medicine socially precise. take a deep breath. Am. J. Respir. Crit. Care Med. 193, 348–350 (2016).
pubmed: 26871667
pmcid: 4803087
Chan, R., Stewart, K., Misirovs, R. & Lipworth, B. J. Targeting downstream type 2 cytokines or upstream epithelial alarmins for severe asthma. J. Allergy Clin. Immunol. Pract. 10, 1497–1505 (2022).
pubmed: 35131510
Varricchi, G. et al. Biologics and airway remodeling in severe asthma. Allergy 77, 3538–3552 (2022).
pubmed: 35950646