Summary Background The prevalence of allergic rhinoconjunctivitis has increased dramatically. Seventeen million people in the United Kingdom, Germany, the Netherlands, Sweden, Denmark, Norway and Finland suffer from grass pollen induced allergic rhinitis. Symptomatic therapy with antihistamines and topical steroids is partially effective but allergen-specific immunotherapy by injection or sublingual routes is superior. The grass allergen tablet (GRAZAX®) is a new allergen-specific immunotherapy for home administration. Objective To assess the cost-effectiveness of the grass allergen tablet compared with symptomatic medication in seven Northern European countries. Methods A prospective pharmacoeconomic analysis was carried out alongside a multinational clinical trial. Pooled data on resource use and health outcomes were collected. A societal perspective was adopted, and the analysis had a 9-year time horizon. The outcome measure was Quality Adjusted Life Years (QALYs). Results The grass allergen tablet was clinically superior to symptomatic treatment, producing statistically significant differences for all efficacy end-points, including the number of QALYs gained - 0.976 vs. 0.947 QALYs gained. There was a significantly higher usage of the rescue medications loratadine and budesonide, and more hours missed from work (production loss), in the symptomatic treatment group. The cost per QALY gained in the grass allergen tablet group was similar in the seven countries (€12 930 to €18 263 for an annual cost of the grass allergen tablet of €1500). The analysis showed that the grass allergen tablet was cost-effective for all countries for an annual treatment cost below €2200. Conclusion The pharmacoeconomic analysis illustrated that allergen-specific immunotherapy with the grass allergen tablet is a cost-effective intervention for the prevention of grass pollen induced rhinoconjunctivitis in Northern European countries, for a tablet price below €6. In Germany for example the price of the tablet is €2.95 corresponding to a yearly treatment cost of €358 - based on a 9-year time horizon.
Background Synthetic peptide immunoregulatory epitopes are a new class of immunotherapy to treat allergic rhinoconjunctivitis (ARC). Grass allergen peptides, comprising 7 synthetic T-cell epitopes derived from Cyn d 1, Lol p 5, Dac g 5, Hol l 5, and Phl p 5, is investigated for treatment of grass pollen–induced ARC. Objective We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides. Methods A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen–induced allergy (18-65 years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6 nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12 nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12 nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed. Results Two hundred eighty-two subjects were randomized. Significantly greater improvement (reduction of total rhinoconjunctivitis symptom score from baseline to PTC) occurred across days 2 to 4 with grass allergen peptide 8x6Q2W versus placebo (−5.4 vs −3.8, respectively; P = .0346). Greater improvement at PTC also occurred for grass allergen peptide 8x6Q2W versus placebo ( P = .0403) in patients with more symptomatic ARC. No safety signals were detected. Conclusion Grass allergen peptide 8x6Q2W significantly improved ARC symptoms after rye grass allergen challenge in an EEU with an acceptable safety profile.
A new freshwater cultivation species, crisp grass carp (CGC; Ctenopharyngodon idellus C. et V.) has a special texture and is popular with consumers; thus, we should pay close attention to its storage conditions and bacterial degradation. CGC and grass carp (GC; Ctenopharyngodon idellus) were commercialized as fillets and subsequently stored at 4 and 8 degrees C. Microbial growth parameters (total viable counts, psychrotrophic bacteria, and Pseudomonas spp.), physicochemical data (pH and total volatile base nitrogen), and sensory analysis were monitored during the storage period. Dominant microorganisms were identified using a 16S rDNA clone library and restriction fragment length polymorphism (RFLP) analysis after the fillets had spoiled completely. The results showed that Pseudomonas spp. lagged behind the psychrotrophic population and the total viable counts initially and increased more rapidly after storage for 2 days. Total volatile base nitrogen contents were found to increase with storage time in both species, coinciding with ongoing microbial change. The pH results obtained for both species during storage showed an overall increase at the end of storage. Sensory evaluation showed a shelf life of 3 and 6 days for both species at 8 and 4 degrees C, respectively. RFLP analysis of the 16S rDNA clone library revealed that there were seven and five distinct RFLP pattern groups in the microflora of the spoiled CGC and GC fillets, respectively. Through RFLP patterns and 16S rDNA sequencing from the clones, it was determined that CGC fillets stored at 4 degrees C were dominated by Pseudomonas spp. at the point of sensory rejection, whereas GC fillets were dominated by populations affiliated with Pseudomonas sp., Acinetobacter sp., and Aeromonas sp.
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.