Strong Dose-response On Immunoglobulin Makers During a Phase II Allergen Immunotherapy Study With Subcutaneously Administered Tyrosine Adsorbed Modified Grass Allergen + MPL

Abstract

RATIONALE: The results of this Phase II study [EudraCT 2017-000333-31] evaluated the dose response relationship for a modified grass allergen subcutaneous immunotherapy (SCIT) product (1.0 ml) with modified allergen tyrosine adsorbate (MATA) and monophosphoryl lipid A (MPL) adjuvants for the treatment of allergic rhinoconjunctivitis (ARC) due to grass pollen. METHODS: In total 447 patients with grass pollen-induced ARC were enrolled in this randomized, double-blind, placebo-controlled, parallel group study. Patients were randomized to one of five dose regimens of 5100, 14400, 27600 and 35600 SU and placebo. As a secondary endpoint the immunoglobulin markers (total IgE, grass-specific IgE, grass-specific IgG4 and specific IgE/total IgE ratio) were evaluated. RESULTS: For all immunoglobulin markers a strong statistically significant dose-response was shown for a wide range of cumulative doses from 5100 SU to 35600 SU. Grass-specific IgE, grass-specific IgG4 and specific IgE/total IgE ratio demonstrated statistically significant increases compared to placebo for all cumulative doses (P<0.01), including the currently marketed dose of 5100 SU in Europe. CONCLUSIONS: An ultra-short course of 6 injections with allergoid grass SCIT treatment with adjuvants MATA and MPL is associated with significant increases in immunoglobulin markers for a wide range of cumulative dose levels indicating a strong therapeutic response. RATIONALE: In the U.S., subcutaneous immunotherapy (SCIT) doses are typically prepared by medical staff removing a given volume from an extract vial at a patient's injection visit. We report a novel methodology using pharmacist-prepared individual SCIT doses at an urban county hospital. METHODS: SCIT extracts are prepared by a pharmacist using dosing recommendations in the U.S. practice parameters. Individual SCIT doses are prepared by a pharmacist prior to a patient's appointment based on the patient's dosing schedule. Doses are placed in labeled syringes in patientspecific baggies. Nurses administer the pre-filled syringes to patients at their appointment. We analyzed data from January 2014 to July 2018 using this methodology. RESULTS: A total of 4203 doses were prepared; 3811 (90.6%) injections were given and 54 doses were held (1.2% of doses prepared). There were a total of 2323 patient appointments and 191 missed appointments (8% of total appointments). There were a total of 36 systemic reactions (0.9% of injections given) ranging from grade 1a -2z, with no grade 3-5 reactions. This rate of systemic reactions per injection is similar to what has been reported in the published literature of approximately 0.2% (Cox et al, 2010), and also comparable to previously reported incidences of non-fatal SCIT systemic reactions in two large cohorts. CONCLUSIONS: We describe a unique approach to delivering SCIT doses yielding a low rate of systemic reactions per injection and minimizing dosing errors. This method may be appropriate for multidisciplinary clinics with frequently changing staff to enhance patient sa...