Strong dose response after immunotherapy with PQ grass using conjunctival provocation testing.

Autor:	Zielen S; Medaimun GmbH, Frankfurt am Main, Germany., Kuna P; Poradnia Alergologii i Chorób Płuc Lodz, Poland., Aberer W; Department of Dermatology, Medical University of Graz, Graz, Austria., Lassmann S; Specialist in Otolaryngology, Saalfeld, Germany., Pfaar O; Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Germany., Klimek L; Centre for Rhinology and Allergology, Wiesbaden, Germany., Wade A; Allergy Therapeutics Ltd., Worthing, UK., Kluehr K; Allergy Therapeutics Ltd., Worthing, UK., Raab J; Allergy Therapeutics Ltd., Worthing, UK., Wessiepe D; Metronomia Clinical Research GmbH, Munich, Germany., Lee D; Allergy Therapeutics Ltd., Worthing, UK., Kramer MF; Allergy Therapeutics Ltd., Worthing, UK., Gunawardena K; Allergy Therapeutics Ltd., Worthing, UK., Higenbottam T; Allergy Therapeutics Ltd., Worthing, UK., Heath MD; Allergy Therapeutics Ltd., Worthing, UK., Skinner MA; Allergy Therapeutics Ltd., Worthing, UK., de Kam PJ; Allergy Therapeutics Ltd., Worthing, UK.
Jazyk:	angličtina
Zdroj:	The World Allergy Organization journal [World Allergy Organ J] 2019 Oct 25; Vol. 12 (11), pp. 100075. Date of Electronic Publication: 2019 Oct 25 (Print Publication: 2019).
DOI:	10.1016/j.waojou.2019.100075
Abstrakt:	Background: Pollinex Quattro Grass (PQ Grass) is an effective, well-tolerated, short pre-seasonal subcutaneous immunotherapy to treat seasonal allergic rhinoconjunctivitis (SAR) due to grass pollen. In this Phase II study, 4 cumulative doses of PQ Grass and placebo were evaluated to determine its optimal cumulative dose. Methods: Patients with grass pollen-induced SAR were randomised to either a cumulative dose of PQ Grass (5100, 14400, 27600 and 35600 SU) or placebo, administered as 6 weekly subcutaneous injections over 31-41 days (EudraCT number 2017-000333-31). Standardized conjunctival provocation tests (CPT) using grass pollen allergen extract were performed at screening, baseline and post-treatment to determine the total symptom score (TSS) assessed approximately 4 weeks after dosing. Three models were pre-defined (Emax, logistic, and linear in log-dose model) to evaluate a dose response relationship. Results: In total, 95.5% of the 447 randomized patients received all 6 injections. A highly statistically significant (p < 0.0001), monotonic dose response was observed for all three pre-specified models. All treatment groups showed a statistically significant decrease from baseline in TSS compared to placebo, with the largest decrease observed after 27600 SU (p < 0.0001). The full course of 6 injections was completed by 95.5% of patients. Treatment-emergent adverse events were similar across PQ Grass groups, and mostly mild and transient in nature. Conclusions: PQ Grass demonstrated a strong curvilinear dose response in TSS following CPT without compromising its safety profile. Competing Interests: PJ. de Kam, A. Wade, K. Kluehr, J. Raab, D. Lee, M.F. Kramer, T. Higenbottam, M.D Heath, and M.A Skinner are full-time employees of Allergy Therapeutics (UK) Ltd. K. Gunawardena is a consultant working for Allergy Therapeutics (UK) Ltd. D. Wessiepe reported fees from Allergy Therapeutics Plc. to her employer Metronomia, during the conduct of the study. Dr. Pfaar reported grants and/or personal fees from ALK-Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, Biomay, Nuvo, Circassia, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Novartis Pharma MEDA Pharma, Anergis S.A., Mobile Chamber Experts (a GA2LEN Partner), Pohl-Boskamp, Indoor Biotechnologies, and GlaxoSmithKline, outside of the submitted work. Dr. Zielen, reports personal fees from Aimmune, during the conduct of the study; grants and personal fees from bene-Arzneimittel GmbH, grants and personal fees from Biotest GmbH, grants from Vifor Pharma Deutschland GmbH, grants from ALK Arzneimittel, personal fees from Novartis GmbH, personal fees from Böhringer Ingelheim, personal fees from Lofarma GmbH, personal fees from IMS HEALTH GmbH & Co. OHG, personal fees from GSK, personal fees from Stallergen, personal fees from Procter and Gamble, personal fees from Allergopharma GmbH, personal fees from Allergy Therapeutics, outside the submitted work. P. Kuna has received lecture fees from Adamed, Allergopharma, AstraZeneca, Berlin Chemie, Boehringer Ingelheim, Chiesi, FAES, Novartis, and Polpharma W. Aberer has not conflict-of-Interest regarding this publication/study. L. Klimek has received research grants from Allergy Therapeutics/Bencard, Great Britain/Germany; ALK-Abelló, Denmark; Allergopharma, Germany; ASIT Biotech, Belgium; Bionorica, Germany; Biomay, Austria, Boehringer Ingelheim, Germany, Circassia, USA; Stallergenes, France; Cytos, Switzerland; Curalogic, Denmark; HAL, Netherlands; Hartington, Spain; Lofarma, Italy; MEDA/Mylan, Sweden/USA; Novartis, Switzerland, Leti, Spain; ROXALL, Germany; GlaxoSmithKline (GSK), Great Britain; Sanofi, France and/or has served on the speaker's bureau or was consulting for the above mentioned pharmaceutical companies. S. Lassmann has received grants and non-financial support from Allergy Therapeutics, during the conduct of the study. (© 2019 The Author(s).)
Databáze:	MEDLINE
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