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Type 2 chronic inflammatory diseases: targets, therapies and unmet needs

Nature Reviews Drug Discovery volume 22, pages 743–767 (2023)Cite this article

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Abstract

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.

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Fig. 1: Environmental triggers of type 2 chronic inflammatory diseases.
Fig. 2: Interaction between cells involved in the pathogenesis of type 2 inflammatory diseases and targets for available and future therapy.
Fig. 3: Targeted treatments approved or in clinical trials for type 2 chronic inflammatory diseases.

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Authors and Affiliations

  1. Institute of Allergology, Charité — Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany

    Pavel Kolkhir, Martin Metz, Torsten Zuberbier & Marcus Maurer

  2. Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Allergology and Immunology, Berlin, Germany

    Pavel Kolkhir, Martin Metz, Torsten Zuberbier & Marcus Maurer

  3. Swiss Institute of Allergy and Asthma Research (SIAF) Davos, University of Zürich, Davos, Switzerland

    Cezmi A. Akdis & Mübeccel Akdis

  4. Department of Otorhinolaryngology — Head and Neck Surgery, University Hospital of Münster, Münster, Germany

    Claus Bachert

  5. Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Claus Bachert

  6. Division of ENT diseases, Karolinska Hospital, Stockholm, Sweden

    Claus Bachert

  7. Department of Dermatology and Allergy, University Hospital, Bonn, Germany

    Thomas Bieber

  8. Christine Kühne-Center for Allergy Research and Education, Davos, Switzerland

    Thomas Bieber

  9. Davos Biosciences, Davos, Switzerland

    Thomas Bieber

  10. Department of Biomedical Sciences, Humanitas University, Milan, Italy

    Giorgio Walter Canonica

  11. Asthma & Allergy Unit, IRCCS Humanitas Research Hospital, Milan, Italy

    Giorgio Walter Canonica

  12. Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York City, NY, USA

    Emma Guttman-Yassky

  13. Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic Barcelona, FRCB-IDIBAPS, Universitat de Barcelona, CIBERES, Barcelona, Spain

    Joaquim Mullol

  14. Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University of Madrid, Madrid, Spain

    Oscar Palomares

  15. Institute of Laboratory Medicine, member of the German Center for Lung Research (DZL) and the Universities of Giessen and Marburg Lung Center (UGMLC), Philipps-University Marburg, Marburg, Germany

    Harald Renz

  16. Kilimanjaro Christian Medical University College (KCMUCo), Moshi, Tanzania

    Harald Renz

  17. Section Pruritus Medicine, Department of Dermatology and Center for Chronic Pruritus, University Hospital Münster, Münster, Germany

    Sonja Ständer

Authors
  1. Pavel Kolkhir
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  2. Cezmi A. Akdis
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  3. Mübeccel Akdis
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  4. Claus Bachert
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  5. Thomas Bieber
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  6. Giorgio Walter Canonica
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  7. Emma Guttman-Yassky
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  8. Martin Metz
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  9. Joaquim Mullol
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  10. Oscar Palomares
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  11. Harald Renz
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  12. Sonja Ständer
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  13. Torsten Zuberbier
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  14. Marcus Maurer
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Corresponding authors

Correspondence to Pavel Kolkhir or Marcus Maurer.

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Competing interests

P.K. received speaker’s fees, honoraria or travel support from Novartis, ValenzaBio, Roche and Takeda. C.A.A. has received research grants from the Swiss National Science Foundation, European Union (EU CURE, EU SynAir-G), Novartis Research Institutes (Basel, Switzerland), Stanford University (Redwood City, CA, USA), Seed Health (Boston, MA, USA) and SciBase (Stockholm, Sweden); is the Co-Chair for European Academy of Allergy and Clinical Immunology (EAACI) Guidelines on Environmental Science in Allergic diseases and Asthma; is Chair of the EAACI Epithelial Cell Biology Working Group; is on the Advisory Boards of Sanofi/Regeneron (Bern, Switzerland, New York, USA), Stanford University Sean Parker Asthma Allergy Center (CA, USA), Novartis (Basel, Switzerland), Glaxo Smith Kline (Zurich, Switzerland), Bristol-Myers Squibb (New York, USA), Seed Health (Boston, MA, USA) and SciBase (Stockholm, Sweden); and is Editor-in-Chief of Allergy. M.A. received research grants from Swiss National Foundation Sean Parker allergy centre Seed grant, Leading House Swiss-Columbia research grant, Horizon 2020 and EU Grant SynAir-G; and is on the advisory board for LEO foundation, SIC Copenhagen, Denmark and Sean Parker Allergy Center (Stanford, CA, USA). C.B. is an Advisory Board member and speaker for Novartis, GSK, AstraZeneca, Sanofi, ALK, Bionorica and Mylan. T.B. was speaker and/or consultant and/or investigator for AbbVie, Affibody, Almirall, AnaptysBio, AOBiom, Arena, Aristea, Asana Biosciences, ASLAN Pharma, Bayer Health, BioVerSys, Böhringer-Ingelheim, Bristol-Myers Squibb, Connect Pharma, Daichi-Sanyko, Dermavant, DIECE Therapeutics, Domain Therapeutics, DS Pharma, EQRx, Galderma, Galapagos, Glenmark, GSK, Incyte, Innovaderm, Janssen, Kirin, Kymab, LEO, LG Chem, Lilly, L’Oréal, MSD, Medac, Novartis, Numab, OM Pharma, Pfizer, Pierre Fabre, Q32bio, RAPT, Sanofi/Regeneron, UCB and Union Therapeutics; and is founder and chairman of the board of the non-profit biotech ‘Davos Biosciences’ within the international Kühne-Foundation. G.W.C. received research grants from as well as being a lecturer for or having received advisory board fees from A. Menarini, Anallergo, Allergy Therapeutics, AstraZeneca, Chiesi Farmaceutici, Faes, Firma, Genentech, Guidotti-Malesci, Glaxo Smith Kline, Hal Allergy, Innovacaremd, Novartis, Om Pharma, RedMaple, Sanofi-Aventis, Sanofi-Genzyme, Stallergenes-Greer, Uriach Pharma, ThermoFisher and Valeas. E.G.-Y. received research grants (paid to the institution) from Boerhinger-Ingelhiem, Leo Pharma, Pfizer, Cara Therapeutics, UCB, Kyowa Kirin, RAPT, Amgen, GSK, Incyte, Sanofi, Bristol Meyers Squibb, Aslan, Regeneron, Anaptysbio, Concert and Janssen. M. Metz has honoraria as a speaker and/or consultant for AbbVie, Amgen, ArgenX, AstraZeneca, Bayer, Celldex, Celgene, Escient, Galderma, Grünenthal, GSK, Menlo, Novartis, Pfizer, Pharvaris, Regeneron, Roche, Sanofi-Aventis, Teva, Third Harmonic Bio and Viforpharma. J.M. is or has been a member of national and international scientific advisory boards, consulted and received fees for lectures and grants for research projects or clinical trials from AstraZeneca, Genentech-Roche, GSK, LETI, Menarini, MSD, Mitsubishi-Tanabe, Viatris/MEDA Pharma, Novartis, OPTINOSE, Proctor & Gamble, Sanofi-Genzyme & Regeneron, UCB Pharma and NOUCOR/Uriach Group; received financial support from AGAUR and ISCiii; and is Editor-in-Chief of Current Treatment Options in Allergy. O.P. has received fees for lectures or participation in Advisory Boards from AstraZeneca, GSK, Inmunotek SL, Novartis, Pfizer, Sanofi-Genzyme and Regeneron; and has received research grants from MINECO, MICINNIN and CAM and research unrestricted grants from Inmunotek SL, Novartis SL and AstraZeneca. H.R. is supported by the German Lung Center (DZL) and the Universities Giessen and Marburg Lung Center (UGLMC), the MIRACUM Consortium of the Medical Informatics Initiative, the Stiftung Pathobiochemistry and DAAD and GIZ Hospital Partnership Programme, the DFG, BMBF, EU and Land Hessen; has received speakers’ honorarium from Allergopharma, Novartis, ThermoFisher, Danone, Bencard and Stallergenes; has consulted for Sterna-biologicals (co-founder); and is Associate Editor of Journal of Allergy and Clinical Immunology (JACI). S.S. was speaker and/or consultant and/or investigator for and/or has received research funding from Abbvie, Almirall, Beiersdorf, BMS, Clexio, Eli Lilly, FomF, Galderma, German Research Foundation (DFG), Integrity CE, Kiniksa, Leo Pharma, L’Oréal, MEDahead, Moroscience, NACCME, Novartis, Omnicuris, P.G. Unna Academy, Pfizer, Sanofi, TouchIME, UCB, Vifor and WebMD. T.Z. has received industry consulting, research grants and/or honoraria from Abivax, Allakos, AImmune, Ajanta Pharma, AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, BioCryst, Celldex, FAES, HAL, Henkel, Kryolan, Leti, Lofarma, L’Oreal, Meda, Medi Wound, Menarini, Merck, MibeTec, MMV Medicines for Malaria Venture, MSD, Novartis, PCM Scientific, Pfizer, Sanofi, Sanoflore, Stallergenes, Takeda, Teva and UCB. M. Maurer is or recently was a speaker and/or adviser for and/or has received research funding from Astria, Allakos, Alnylam, Amgen, Aralez, ArgenX, AstraZeneca, BioCryst, Blueprint, Celldex, Centogene, CSL Behring, Dyax, FAES, Genentech, GIInnovation, GSK, Innate Pharma, Kalvista, Kyowa Kirin, Leo Pharma, Lilly, Menarini, Moxie, Novartis, Pfizer, Pharming, Pharvaris, Roche, Sanofi/Regeneron, Shire/Takeda, Third Harmonic Bio, UCB and Uriach.

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Glossary

Biomarkers

Measurable indicators linking disease endotypes with phenotypes.

Disease-modifying treatments

Therapies that affect the disease course — for example, delay or slow the progression of the disease or lead to a long-term reduction in symptoms — by targeting its underlying mechanism.

Endotypes

Subtypes of a disease, which are characterized by a distinct pathophysiologic mechanism at a cellular and a molecular level.

Phenotypes

Clusters of visible properties, attempting to individualize disease expression in a group of patients.

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Kolkhir, P., Akdis, C.A., Akdis, M. et al. Type 2 chronic inflammatory diseases: targets, therapies and unmet needs. Nat Rev Drug Discov 22, 743–767 (2023). https://doi.org/10.1038/s41573-023-00750-1

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