Design of an Optimally-Diagnostic Skin Test for Diagnosis of Sensitivity to Eight Allergens: A First-in-Human Study of Dose Escalation and Simultaneous Administration in Chinese Subjects

Abstract

Xiaoyi Ning,1,* Yun Kuang,1,* Shuwei Zhao,2 Wenjing Hou,2 Guoping Yang,1,3,4 Xuerui Zhu,5 Ruiling Liu,6 Jie Huang1 1Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Center of Clinical Medical Trial, Medical University General Hospital, Tianjin, People’s Republic of China; 3Research Center for Drug Clinical Evaluation of Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Department of clinical research and development, Zhejiang Wolwo Biopharmaceuticals, Deqing, Zhejiang, People’s Republic of China; 6Department of Allergy, Medical University General Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruiling LiuDepartment of Allergy, Medical University General Hospital, Tianjin 300052, People’s Republic of ChinaTel/Fax [phone]Email [email protected] HuangCenter for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, 138 TongZiPo Road, Changsha, Hunan 410013, People’s Republic of ChinaTel/Fax [phone]Email [email protected]: Eight extracts from common native allergens, Artemisia annua pollen, Platanus pollen, Humulus pollen, Betula platyphylla pollen, Ambrosia artemisiifolia pollen, Blattella germanica, cat dander and dog dander were developed for skin prick test (SPT). Since standardization and composition alone cannot guarantee that the allergen extracts are within the concentration range that give the best chance of a true diagnosis, it is necessary to explore the optimal diagnostic concentration (ODC) of allergens in SPT.Objective: To identify the optimal diagnostic concentration of eight allergen extracts in SPT and assess the safety of simultaneous administration.Patients and Methods: Patients with a history of allergic disease were enrolled in this two-part open-label, parallel study. In Study 1, 92 patients were enrolled into eight groups according to their disease-causing allergens and were given three increasing concentrations of the corresponding allergen. In Study 2, 20 patients were divided into two concentration groups and were given all of the eight allergens. Safety and sensitivity were evaluated to determine the optimal diagnostic concentration.Results: In Study 1, the sensitivity of seven allergen extracts was > 80% at middle and high concentrations, except for Ambrosia artemisiifolia pollen. The optimal diagnostic concentration (in DU/mL) for eight allergens was 33,333, 12,000, 8667, 50,000, 40,000, 3333, 7000, and 5000. In Study 2, the prevalence of adverse events in the two groups was 70% and 80%, respectively. A total of 10 wheals of 8 patients did not subside < 24 h after SPTs.Conclusion: The eight allergens showed high sensitivity and safety at a certain concentration, which was defined as optimal diagnostic concentration. The results support further clinical research of investigated allergens and our study offers a scheme to determine the ODC of allergens in SPT.Keywords: skin prick test, allergen, optimal diagnostic concentration

Keywords

• : skin prick test
• allergen
• optimal diagnostic concentration