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Background: This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abelló A/S, Hørsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy. Objective: We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons. Methods: The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen. Participants were treated with active (n = 189) or placebo (n = 162) tablets for an average of 22 months. All participants were allowed to use symptomatic rescue medication. Results: The primary efficacy analysis showed highly significant mean reductions of 36% in rhinoconjunctivitis symptom score (P < .0001; median reduction, 44%) and 46% in rhinoconjunctivitis medication score (P < .0001; median reduction, 73%) in the active group relative to the placebo group. Mean rhinoconjunctivitis quality of life was 33% better (P < .0001; median, 40%). Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins. The treatment was well tolerated, and adverse events led to withdrawal in less than 1% of participants. There were no serious adverse events related to treatment. Conclusion: Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment. [Copyright &y& Elsevier]

Background: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. Objective: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abelló, Hørsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. Methods: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen–induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. Results: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. Conclusion: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen–induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. Clinical implications: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use. [Copyright &y& Elsevier]

Background The SQ HDM SLIT-tablet (ALK) has been developed for treatment of house dust mite (HDM)–induced respiratory allergic disease. Objective This trial investigated the efficacy and safety of the SQ HDM SLIT-tablet in adults with moderate-to-severe HDM-induced allergic rhinitis (AR). Methods The trial was a randomized, double-blind, placebo-controlled phase III trial conducted in 12 European countries including 992 adults with moderate-to-severe HDM-induced AR despite treatment with pharmacotherapy. Subjects were randomized 1:1:1 to 1 year of daily treatment with placebo, 6 SQ-HDM, or 12 SQ-HDM. The primary end point was the total combined rhinitis score (ie, the sum of rhinitis symptom and medication scores) during the efficacy assessment period (approximately the last 8 weeks of the treatment period). Key secondary end points were rhinitis symptoms, medication scores, quality of life, and the combined rhinoconjunctivitis score. Results Analysis of the primary end point (observed data) demonstrated absolute reductions in total combined rhinitis score of 1.18 ( P = .002) and 1.22 ( P = .001) compared with placebo for 6 SQ-HDM and 12 SQ-HDM, respectively. The statistically significant treatment effect was evident from 14 weeks of treatment onward. For all key secondary end points, efficacy was confirmed for 12 SQ-HDM, with statistically significant reductions of rhinitis symptoms and medication scores, improved quality of life, and a reduced combined rhinoconjunctivitis score in the efficacy assessment period compared with placebo. The treatment was well tolerated. Conclusion The trial confirmed the efficacy and favorable safety profile of both 6 SQ-HDM and 12 SQ-HDM in adults with HDM-induced AR. The treatment effect was present from 14 weeks of treatment onward. [ABSTRACT FROM AUTHOR]

Background: The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials. Objective: To investigate sustained efficacy and disease modification in a 5-year double-blind, placebo-controlled trial, including 2 years of blinded follow-up after completion of a 3-year period of treatment, with the SQ-standardized grass allergy immunotherapy tablet, Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU, ∗ [∗] SQ-T (standardized quality tablet units) and BAU (biological activity units) are quantitative measures of biological activity; ie, the potency of allergen extracts/vaccines. One grass AIT contains 75,000 SQ-T of timothy (Phleum pratense) grass pollen extract (measure of total biological potency using ALK in-house reference), equivalent to 2,800 BAU (measure of total biological potency, defined by the FDA). ALK, Denmark) or placebo. Methods: A randomized, double-blind, placebo-controlled, multinational, phase III trial included adults with a history of moderate-to-severe grass pollen–induced allergic rhinoconjunctivitis, with or without asthma, inadequately controlled by symptomatic medications. Two hundred thirty-eight participants completed the trial. End points included rhinoconjunctivitis symptom and medication scores, combined scores, asthma symptom and medication scores, quality of life, days with severe symptoms, immunologic end points, and safety parameters. Results: The mean rhinoconjunctivitis daily symptom score was reduced by 25% to 36% (P ≤ .004) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial. The rhinoconjunctivitis DMS was reduced by 20% to 45% (P ≤ .022 for seasons 1-4; P = .114 for season 5), and the weighted rhinoconjunctivitis combined score was reduced by 27% to 41% (P ≤ .003) in favor of active treatment. The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group, with relative differences of 49% to 63% (P ≤ .0001). Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response. No safety issues were identified. Conclusion: The results confirm disease modification by SQ-standardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis. [Copyright &y& Elsevier]

Background: Sustained and disease-modifying effects of sublingual immunotherapy have never before been confirmed in a large-scale randomized, double-blind, placebo-controlled trial. Objective: We sought to investigate sustained efficacy 1 year after a 3-year period of daily treatment with the SQ-standardized grass allergy immunotherapy tablet Grazax (Phleum pratense 75,000 SQ-T/2,800 BAU; ALK-Abelló, Hørsholm, Denmark). Methods: A randomized, double-blind, placebo-controlled, phase III trial including adults with a history of moderate-to-severe grass pollen induced rhinoconjunctivitis inadequately controlled by symptomatic medications. The analysis set comprised 257 subjects at the follow-up. Efficacy end points were rhinoconjunctivitis symptom and medication scores, quality of life, and percentages of symptom and medication free days. Immunologic end points included grass pollen–specific serum IgG4 and IgE-blocking factor. Safety was assessed based on adverse events. Results: Significant improvements in efficacy were consistently shown during 3 years'' treatment. One year after treatment, the active group showed sustained reductions in mean rhinoconjunctivitis symptom scores (26%, P < .001) and medication scores (29%, P = .022) when compared with placebo. This level was similar to the efficacy observed during the 3-year treatment period. The differences in percentages of symptom- and medication-free days were significant during and 1 year after treatment. The active group also reported sustained and significant improvements in quality of life. Sustained clinical benefit was accompanied by immunologic changes. No safety issues were identified. Conclusion: Three years of treatment with the SQ-standardized grass allergy immunotherapy tablet resulted in consistent clinical improvement and accompanying immunologic changes that were sustained 1 year after treatment, which is indicative of disease modification and associated long-term benefits. [Copyright &y& Elsevier]

Abstract: 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 enrolled. 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 IgG4 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 IgG4 concentrations were significantly greater with AIT compared with placebo (IgE, +0.59 vs +0.21 log kU/L; IgG4, +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 IgG4. 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. [Copyright &y& Elsevier]