Immunologic Effects and Tolerability Profile of In-Season Initiation of a Standardized-Quality Grass Allergy Immunotherapy Tablet: A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial in Adults with Grass Pollen Induced Rhinoconjunctivitis

Background: The summary of product characteristics of the grass allergy immunotherapy tablet (AIT) (Phleum pratense grass pollen allergen extract) states that clinical effect may be observed in the first pollen season of treatment, if treatment is initiated >= 2 months (8 weeks) before the start of the grass pollen season. However, because patients with grass allergy may first present to physicians during the season, immediate treatment initiation (ie, in-season initiation) may increase treatment compliance and reduce the risk for disease progression compared with asking patients to return before the next pollen season to initiate treatment. This "in-season approach" may offer more patients the potentially beneficial treatment option of specific immunotherapy. However, to date, the immunomodulatory effects and tolerability of in-season treatment initiation is unknown. Objective: The aim of this study was to assess the immunologic effects and tolerability of in-season initiation of treatment with the grass AIT. Methods: This multicenter, randomized, double-blind, placebo-controlled trial was carried out in Germany and Austria. Adults with grass pollen allergy (positive skin-prick test and specific grass-pollen immunoglobulin [Ig] E) and grass pollen induced moderate to severe persistent rhinoconjunctivitis were en-rolled. Patients were randomly assigned to receive once-daily grass AIT or placebo, starting during the 2008 grass pollen season and continuing for 8 to 10 weeks. The primary end point was change from baseline in IgE-blocking factor (serum components competing with IgE for allergen binding). Secondary end points included changes from baseline in specific IgE and IgG(4) and measures of tolerability (assessed mainly by adverse events [AEs]). Blood samples for immunologic assessment were obtained by the investigators at baseline and after treatment. All AEs observed by the investigator and/or reported by the patient were recorded throughout the trial and follow-up. Results: A total of 276 patients were enrolled and formed the full analysis set (mean age, 35 years; 55% men, 45% women; 99% white; mean weight, 76 kg; history of asthma, 41%; mean duration of grass allergy, 15.1 years). No major differences in medical history were found between the grass AIT group (n = 219) and the placebo group (n = 57). The change from baseline in mean concentration of IgE-blocking factor was significantly greater with grass AIT compared with placebo (+0.14 vs +0.05; P < 0.0001). The changes from baseline in specific IgE and specific IgG(4) concentrations were significantly greater with AIT compared with placebo (IgE, +0.59 vs +0.21 log kU/L; IgG(4), +0.18 vs +0.04 log relative units; both, P < 0.0001). At least 1 AE was reported in 58% of patients in the AIT group and in 40% of patients in the placebo group. Most AEs considered related to AIT were mild or moderate events in the mouth, throat, and/or ears (eg, oral pruritus). Four serious AEs were reported in the AIT group (sinusitis, road traffic accident, salmonellosis, meniscus lesion), but all were considered unlikely to be related to treatment. Three percent of the grass AIT group and 2% of the placebo group were withdrawn from the trial due to an AE. Conclusions: In-season initiation of grass AIT was associated with an immunomodulatory response in terms of induction of IgE-blocking factor, specific IgE, and specific IgG(4). In-season initiation of grass AIT was generally well tolerated in this group of adults with moderate to severe grass pollen-induced rhinoconjunctivitis. These findings are consistent with those related to the preseasonal initiation of AIT therapy. ClinicalTrials.gov identifier: NCT00773240. (Clin Ther. 2011;33:828-840) (C) 2011 Elsevier HS Journals, Inc. All rights reserved.