De Kam, Pieter-Jan, Kramer, Matthias F. ORCID: 0000-0002-3740-4733, Shamji, Mohamed H., Oluwayi, Kemi, Heath, Matthew D., Jensen-Jarolim, Erika, Berger, Markus H., Berger, Uwe E., Graessel, Anke ORCID: 0000-0001-9670-3269, Sellwood, Fiona, Zielen, Stefan, Vogelberg, Christian, Zieglmayer, Petra, Mosges, Ralph, Klimek, Ludger, DuBuske, Lawrence M., Shreffler, Wayne G., Bernstein, Jonathan A., Kundig, Thomas M. and Skinner, Murray A. (2021). Dogmas, challenges, and promises in phase III allergen immunotherapy studies. World Allergy Organ. J., 14 (9). AMSTERDAM: ELSEVIER. ISSN 1939-4551

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Abstract

The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries. Moreover, most of these AIT products are provided on an individual patient basis as named patient products (NPP) in Europe, while individualized preparations of (mixed) allergenic extract vials for subcutaneous administration (compounding) is common practice in the US. AIT products are generally considered safe and well tolerated, but the major practical clinical development challenge is to define the optimal dose and prove the efficacy and safety of these products using state-of-the art Phase II and pivotal Phase III studies. In planning Phase II-III AIT studies, a thorough understanding of the study challenges is essential (e.g. variability and non-validated status of subjective primary endpoints, limitations of pollen season definitions) and dogmas of these products (e.g., for sublingual immunotherapy (SLIT) trials double-blinding conditions cannot be maintained, resulting in stronger placebo responses in the active treatment group and inflated treatment effects in Phase III). There is future promise for more objective biomarker endpoints (e.g. basophil activation (CD63 and CD203c), subsets of regulatory dendritic, T and B cells, IL-10- producing group 2 innate lymphoid cells; alone or in combination) to overcome several of these dogmas and challenges; innovation in AIT clinical trials can only progress with integral biomarker research to complement the traditional endpoints in Phase II-III clinical development. The aim of this paper is to provide an overview of these dogmas, challenges and recommendations based on published data, to facilitate the design of Phase III studies and improve the evidence basis of safe and effective AIT products.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
De Kam, Pieter-JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kramer, Matthias F.UNSPECIFIEDorcid.org/0000-0002-3740-4733UNSPECIFIED
Shamji, Mohamed H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oluwayi, KemiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heath, Matthew D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jensen-Jarolim, ErikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berger, Markus H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berger, Uwe E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Graessel, AnkeUNSPECIFIEDorcid.org/0000-0001-9670-3269UNSPECIFIED
Sellwood, FionaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zielen, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogelberg, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zieglmayer, PetraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mosges, RalphUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klimek, LudgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
DuBuske, Lawrence M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shreffler, Wayne G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernstein, Jonathan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kundig, Thomas M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Skinner, Murray A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-603809
DOI: 10.1016/j.waojou.2021.100578
Journal or Publication Title: World Allergy Organ. J.
Volume: 14
Number: 9
Date: 2021
Publisher: ELSEVIER
Place of Publication: AMSTERDAM
ISSN: 1939-4551
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GRASS-POLLEN IMMUNOTHERAPY; CLINICAL-TRIALS; DOUBLE-BLIND; SUBCUTANEOUS IMMUNOTHERAPY; SLIT-TABLET; EFFICACY; PLACEBO; RHINOCONJUNCTIVITIS; SAFETY; RHINITISMultiple languages
Allergy; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60380

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