ABSTRACT
BACKGROUND: Early pollen flight and new allergens prolonging the pollen season means that the time for up-dosing of allergen-specific subcutaneous immunotherapy (SCIT) outside the pollen season becomes shorter. Hence, for patients who wish or need to be up-dosed faster, an accelerated induction regimen would provide a useful treatment option. METHODS: An accelerated up-dosing regimen (0.1-0.3-0.5 mL at weekly intervals) was compared to conventional up-dosing (0.05-0.1-0.2-0.3-0.4-0.5 mL at weekly intervals) using an allergoid birch pollen SCIT preparation. After up-dosing, the maintenance dose (0.5 mL) was given 3 times at biweekly intervals. The multicenter study was performed according to an open randomized, parallel-group design. RESULTS: A total of 123 birch pollen-allergic patients (81 adults and 42 adolescents) presenting with rhinitis or rhinoconjunctivitis with or without mild asthma (FEV1 >70%) were randomized to either the conventional registered up-dosing or an accelerated regimen. In total, 96.7 and 98.4% successfully reached the maintenance dose for the conventional and accelerated regimen, respectively, without relevant differences between adults and adolescents. Both regimens were safe and well tolerated. Furthermore, significant increases (similar in size) in specific IgG and IgG4 after 3 months of treatment were observed in both groups, independent of age. CONCLUSION: The accelerated SCIT regimen was revealed to be as safe as the conventional regimen, and the immunological effects of both regimens are similar. Accordingly, the accelerated regimen may be used to up-dose patients of adult as well adolescent age within 2 weeks.
Subject(s)
Allergens/administration & dosage , Asthma/therapy , Betula/immunology , Conjunctivitis, Allergic/therapy , Desensitization, Immunologic/methods , Rhinitis, Allergic, Seasonal/therapy , Administration, Cutaneous , Adolescent , Adult , Allergens/adverse effects , Allergens/immunology , Antigens, Plant/adverse effects , Antigens, Plant/immunology , Asthma/immunology , Betula/adverse effects , Child , Conjunctivitis, Allergic/immunology , Desensitization, Immunologic/adverse effects , Female , Humans , Immunoglobulin E/immunology , Immunoglobulin G/immunology , Male , Middle Aged , Pollen/adverse effects , Pollen/immunology , Rhinitis, Allergic, Seasonal/immunology , Young AdultABSTRACT
In recent years, it has become increasingly important to get as much as possible information on clinical efficacy already in the early phases of drug development. For proof of concept (POC) studies testing novel anti-inflammatory drugs in asthma, there are several validated exacerbation models, inducing various aspects of the airway inflammation and airway responsiveness. The choice of the appropriate asthma model depends on the drug's targets within the inflammatory process. For adequate assessment of the drug's anti-inflammatory potential, it is crucial to choose adequate (surrogate) biomarkers. Ideally, these should include measures of airway response, central and peripheral airway inflammation and airway hyperresponsiveness. Overall, there are validated non-invasive sampling techniques for the measurement of inflammatory markers in asthma that can be applied as outcome parameters in early clinical trials. If adequately implemented, these measurements can provide early indication of proof of pharmacological and potential therapeutic efficacy-even in first administration to humans.
