Treatment of seasonal allergic rhinoconjunctivitis with a once-daily SQ-standardized grass allergy immunotherapy tablet
Specific immunotherapy with the grass allergy immunotherapy tablet (AIT) has been developed as an effective, well tolerated, and convenient treatment for grass pollen induced seasonal allergic rhinoconjunctivitis (ARC). Six phase II/III randomized, placebo-controlled trials with the duration of a single grass pollen season of treatment using the SQ-standardized grass AIT, Grazax (Phleum pratense, 75,000 SQ-T/2,800 BAU, ALK, Denmark), have been published previously. This review compares results from these trials. As outcome measures and methods of assessing them were similar across the trials, we have summarized the main efficacy findings (Total Combined Score [TCS], average daily rhinoconjunctivitis symptom and medication scores, percentage of well days, quality of life scores) during a single season of treatment with grass AIT in adults and children with seasonal ARC. The results of the European and North American trials were similar. Compared with the placebo group, who received symptomatic medications only, treatment with grass AIT resulted in fewer rhinoconjunctivitis symptoms, a lower intake of symptomatic medication, better patient self-rated quality of life and a greater percentage of well days during the entire grass pollen season. The data indicate that grass AIT treatment is equally effective in adults and children; the measured effect varies with pollen exposure, but is comparable across regions and continents, with a consistent difference compared with placebo in TCS that was above 20% for all trials. Local adverse events were experienced by the majority of patients. These reactions were generally mild to moderate in severity and transient in duration. Systemic adverse events were rare. This review confirms SQ-standardized grass AIT as a suitable therapeutic option for seasonal use in patients aged 5 years or older with grass pollen induced ARC.
[Show abstract] [Hide abstract] ABSTRACT: Allergen immunotherapy (AIT) is a guidelines-approved, disease-modifying treatment option for respiratory allergies, including allergic rhinitis (AR) induced by pollen. The various AIT regimens employed to date in pollen-induced AR can be classified as continuous (i.e. year-round) or discontinuous (i.e. pre-seasonal alone, co-seasonal alone or pre- and co-seasonal). Pre-and co-seasonal regimens are typically used for sublingual allergen immunotherapy (SLIT) and have economic and compliance advantages over perennial (year-round) regimens. However, these advantages must not come at the expensive of poor efficacy or safety. The results of recent double-blind, placebo-controlled, randomized clinical trials show that pre- and co-seasonal SLIT is safe and effective in patients with AR induced by grass pollen (treated with a tablet formulation) or by birch pollen (treated with a liquid formulation). Progress in SLIT has been made in defining the optimal dose of major allergen, the administration frequency (daily), the duration of pre-seasonal treatment (four months) and the number of treatment seasons (at least three). Post-marketing, "real-life" trials of pre- and co-seasonal birch or grass pollen SLIT regimens have confirmed the efficacy and safety observed in the clinical trials. In the treatment of pollen-induced AR, pre- and co-seasonal SLIT regimens appear to be at least as effective and safe as perennial SLIT regimens, and are associated with lower costs and good compliance. Good compliance may mean that pre- and co-seasonal SLIT regimens are inherently more effective and safer than perennial SLIT regimens. When considering the pre- and co-seasonal discontinuous regimen in particular, a 300 IR five-grass-pollen formulation is the only SLIT tablet with a clinical development programme having provided evidence of short-term, sustained and post-treatment efficacy.0Comments 4Citations
- "According to the respective manufacturers' in-house assays, the major allergen (Phl p 5) content is 25 μg for the 300 IR fivegrass-pollen SLIT tablet and 15 μg for the 75,000 SQ-T single-grass-pollen SLIT tablet [64,77]. Although these tablets differ in terms of BAUs and major allergen content (for optimal comparisons, these parameters should be determined by the same laboratory in the same patients and using the same reagents [74,78]), the two formulations appear to provide similar efficacy in the first year of Phase III trials (as assessed by the effect size for the rhinoconjunctivitis score, relative to pla- cebo)36373839. When considering pre-and co-seasonal regimens with grass-pollen tablets, only the 300 IR five-grass formulation has proven sustained and posttreatment efficacy in addition to single-season efficacy  . "
[Show abstract] [Hide abstract] ABSTRACT: In this paper, we review the current management of allergic rhinitis and new directions for future treatment. Currently, management includes pharmacotherapy, allergen avoidance and possibly immunotherapy. The simple washing of nasal cavities using isotonic saline provides a significant improvement and is useful, particularly in children. The most effective medication in persistent rhinitis used singly is topical corticosteroid, which decreases all symptoms, including ocular ones. Antihistamines reduce nasal itch, sneeze and rhinorrhea and can be used orally or topically. When intranasal antihistamine is used together with topical corticosteroid, the combination is more effective and acts more rapidly than either drug used alone. Alternative therapies, such as homeopathy, acupuncture and intranasal carbon dioxide, or devices such nasal air filters or intranasal cellulose, have produced some positive results in small trials but are not recommended by Allergic Rhinitis and its Impact on Asthma (ARIA). In the field of allergic immunotherapy, subcutaneous and sublingual routes are currently used, the former being perhaps more efficient and the latter safer. Sublingual tablets are now available. Their efficacy compared to standard routes needs to be evaluated. Efforts have been made to develop more effective and simpler immunotherapy by modifying allergens and developing alternative routes. Standard allergen avoidance procedures used alone do not provide positive results. A comprehensive, multi-trigger, multi-component approach is needed, including avoidance of pollutants such as cigarette smoke.0Comments 4Citations
- "New directions 2011 witnessed an advance in treating allergic rhinitis in the form of sublingual tablets. Today, these tablets are only available for grass-pollen allergy (Figure 2), but there are ongoing clinical trials using house-dust mite and ragweed allergens [17,18]. Using sublingual tablets for adults suffering from mite-allergic rhinitis, Bergmann et al.  showed that they had significant efficacy on allergic symptoms, and demonstrated an increase in specific IgG, and a decrease in mean wheal diameter to miteextracts , while there was no significant difference, compared to the placebo group, on use of rescue medication, which is taken when needed. "
- [Show abstract] [Hide abstract] ABSTRACT: Background The objective was to evaluate the association between grass pollen exposure, allergy symptoms and impact on measured treatment effect after grass sublingual immunotherapy (SLIT)-tablet treatment. Methods The association between grass pollen counts and total combined rhinoconjunctivitis symptom and medication score (TCS) was based on a post hoc analysis of data collected over six trials and seven grass pollen seasons across North America and Europe, including 2363 subjects treated with grass SLIT-tablet or placebo. Daily pollen counts were obtained from centralized pollen databases. The effect of treatment on the relationship between the TCS and pollen counts was investigated, and the relative difference between grass SLIT-tablet and placebo as a function of average grass pollen counts was modelled by linear regression. ResultsThe magnitude of treatment effect based on TCS was greater with higher pollen exposure (P < 0.001). The relative treatment effect in terms of TCS for each trial was correlated with the average grass pollen exposure during the first period of the season, with predicted reduction in TCS = 12% + 0.35% × pollen count (slope significantly different from 0, P = 0.003; R2 = 0.66). Corresponding correlations to the entire grass pollen season and to the peak season were equally good, whereas there was a poor correlation between difference in measured efficacy and pollen exposure during the last part of the season. Conclusions In seasonal allergy trials with grass SLIT-tablet, the observed treatment effect is highly dependent on pollen exposure with the magnitude being greater with higher pollen exposure. This is an important relationship to consider when interpreting individual clinical trial results.0Comments 14Citations