Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis
Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies.
We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR (index of reactivity) 5-grass-pollen SLIT tablets (Oralair) compared with placebo assessed by using the average adjusted symptom score (AAdSS) at season 3 in adults with grass pollen-induced rhinoconjunctivitis.
Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons. The primary outcome was the AAdSS, a symptom score adjusted for rescue medication use, after 3 consecutive treatment seasons. Secondary outcomes were symptoms and rescue medication score, quality-of-life, and safety assessments.
The mean AAdSS was reduced by 36.0% and 34.5% at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups, respectively, compared with that in the placebo group (P < .0001 for both). Reductions were observed in total symptom scores and ISSs and the medication score, with a marked improvement in quality of life for both active groups compared with the placebo group at season 3. Most treatment-emergent adverse events were local reactions expected with SLIT, decreasing in number and intensity in each treatment season.
Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated, with reduction in symptoms and rescue medication use. The treatment was well tolerated. Adverse events decreased in number and intensity over the 3 seasons.
Available from: Philippe Devillier
- "An interesting question relates to whether the RCI for SLIT products and symptomatic medications changes over time during long-term use (that is, from one year or treatment season to another). The multiseason studies of grass pollen SLIT tablets provide a few indications [18,19]. In the trial by Durham et al., the RCIs for the treatment years one, two and three (based on the RTSS) were -0.31, -0.36, and -0.29, respectively . "
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The capacity of sublingual allergen immunotherapy (SLIT) to provide effective symptom relief in pollen-induced seasonal allergic rhinitis is often questioned, despite evidence of clinical efficacy from meta-analyses and well-powered, double-blind, placebo-controlled randomized clinical trials. In the absence of direct, head-to-head, comparative trials of SLIT and symptomatic medication, only indirect comparisons are possible.
We performed a meta-analysis of classes of products (second-generation H1-antihistamines, nasal corticosteroids and grass pollen SLIT tablet formulations) and single products (the azelastine-fluticasone combination MP29-02, and the leukotriene receptor antagonist montelukast) for the treatment of seasonal allergic rhinitis in adults, adolescents and/or children. We searched the literature for large (n >100 in the smallest treatment arm) double-blind, placebo-controlled randomized clinical trials. For each drug or drug class, we performed a meta-analysis of the effect on symptom scores. For each selected trial, we calculated the relative clinical impact (according to a previously published method) on the basis of the reported post-treatment or season-long nasal or total symptom scores: 100 × (scorePlacebo - scoreActive)/scorePlacebo.
Twenty-eight publications on symptomatic medication trials and ten on SLIT trials met our selection criteria (total number of patients: n = 21,223). The Hedges' g values from the meta-analyses confirmed the presence of a treatment effect for all drug classes. In an indirect comparison, the weighted mean (range) relative clinical impacts were -29.6% (-23% to -37%) for five-grass pollen SLIT tablets, -19.2% (-6% to -29%) for timothy pollen SLIT tablets, -23.5% (-7% to -54%) for nasal corticosteroids, -17.1% (-15% to -20%) for MP29-02, -15.0% (-3% to -26%) for H1-antihistamines and -6.5% (-3% to -10%) for montelukast.
In an indirect comparison, grass pollen SLIT tablets had a greater mean relative clinical impact than second-generation antihistamines and montelukast and much the same mean relative clinical impact as nasal corticosteroids. This result was obtained despite the presence of methodological factors that mask the clinical efficacy of SLIT for the treatment of seasonal allergic rhinitis.
BMC Medicine 05/2014; 12(1):71. DOI:10.1186/1741-7015-12-71 · 7.25 Impact Factor
Available from: Sabina Rak
- "The most frequent adverse events were application site reactions (e.g., oral pruritus and throat irritation). Consistent with the published experience with grass pollen sublingual immunotherapy, the incidence of withdrawals due to adverse events decreased from the first treatment period to the second [24,25]. "
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ABSTRACT: Allergic rhinoconjunctivitis (ARC) due to birch pollen is a growing health concern in Europe. Here, we report the efficacy and safety of 300IR birch pollen sublingual solution administered discontinuously for 2 consecutive years to patients with birch-associated allergic rhinoconjunctivitis.
Birch pollen-allergic adults were randomized in this double blind study to 300IR birch pollen sublingual solution or placebo, daily, starting 4 months before and continuing through the pollen season for two pollen seasons. Randomization was stratified according to the presence or absence of oral allergy syndrome (OAS). The primary efficacy endpoint was the Average Adjusted Symptom Score (AAdSS) over the second pollen season and was analyzed by ANCOVA. Secondary efficacy endpoints included the AAdSS over the first pollen period. Safety was evaluated by means of adverse event monitoring.
574 patients (284 in the active group and 290 in the placebo group) were randomized and 496 completed the study. Over the second pollen period, the least square (LS) mean AAdSS was significantly lower in the 300IR group than in the placebo group (LS mean difference -2.04, 95% CI [-2.69, -1.40], (p <0.0001) with a relative reduction of 30.6%. Results were consistent in patients with and without OAS (-33.6% and -28.4%, respectively). A significant reduction in LS mean AAdSS was also observed over the first pollen season. The most frequently reported adverse events were application site reactions: oral pruritus, throat irritation, and mouth edema. There were no reports of anaphylaxis.
Pre- and co-seasonal treatment with 300IR birch pollen sublingual solution demonstrated sustained clinical efficacy over 2 pollen seasons and was well tolerated in adults with birch pollen-associated allergic rhinoconjunctivitis. Efficacy results were consistent in patients with and without oral allergy syndrome.Trial registration: ClinicalTrials.gov: NCT01731249.
02/2014; 4(1):7. DOI:10.1186/2045-7022-4-7
Available from: Anne K Ellis
- "Increased risk with placebo Increased risk with immunotherapy Overall (I 2 = 0.0%, P = 0.572) Nelson, 2011 Frew, 2006 Horak, 2009 ID Drachenberg, 2001 Didier, 2007 Dubuske, 2011 Dahl, 2006a Halken, 2010 Dahl, 2008 Durham, 2010 Bufe, 2009 Didier, 2011 Pfaar, 2012 Durham, 2006 Corrigan, 2005 Frew, 2006 Didier, 2011 Dahl, 2006 Zenner, 1997 Blaiss, 2011 Didier, 2007 Study 2.64 (1.88, 3.72) 1.45 (0.60, 3.54) 8.12 (1.09, 60.37) 0.49 (0.05, 5.20) ES (95% CI) 2.96 (0.12, 71.68) 13.08 (0.74, 230.27) 6.50 (1.47, 28.66) 2.01 (0.87, 4.64) 3.50 (0.74, 16.55) 0.43 (0.04, 4.68) 0.81 (0.05, 12.86) 2.02 (0.38, 10.81) 6.35 (1.90, 21.23) 0.89 (0.17, 4.72) 3.43 (0.72, 16.25) 1.00 (0.02, 49.77) 2.97 (0.31, 28.10) 5.64 (1.67, 19.08) 3.83 (0.20, 72.29) 2.74 (0.11, 65.42) 2.51 (0.91, 6.89) 16.58 (0.97, 284.79) 100.00 14.66 2.89 2.08 Weight 1.15 1.42 5.29 16.73 4.82 2.04 1.53 4.13 7.99 4.18 4.81 0.76 2.31 7.84 1.35 1.16 11.43 1.44 % 2.64 (1.88, 3.72) 1.45 (0.60, 3.54) 8.12 (1.09, 60.37) 0.49 (0.05, 5.20) ES (95% CI) 2.96 (0.12, 71.68) 13.08 (0.74, 230.27) 6.50 (1.47, 28.66) 2.01 (0.87, 4.64) 3.50 (0.74, 16.55) 0.43 (0.04, 4.68) 0.81 (0.05, 12.86) 2.02 (0.38, 10.81) 6.35 (1.90, 21.23) 0.89 (0.17, 4.72) 3.43 (0.72, 16.25) 1.00 (0.02, 49.77) 2.97 (0.31, 28.10) 5.64 (1.67, 19.08) 3.83 (0.20, 72.29) 2.74 (0.11, 65.42) 2.51 (0.91, 6.89) 16.58 (0.97, 284.79) 100.00 14.66 2.89 2.08 Weight 1.15 1.42 5.29 16.73 4.82 2.04 1.53 4.13 7.99 4.18 4.81 0.76 2.31 7.84 1.35 1.16 11.43 1.44 % 1 0.25 0.5 1 2.5 20 Oralair Grazax SCIT Figure 5 "
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ABSTRACT: The standard of preventive care for poorly controlled seasonal allergic rhinitis (AR) is subcutaneous immunotherapy (SCIT) with allergen extracts, administered in a physician's office. As an alternative to SCIT, sublingual immunotherapy (SLIT) is now an option for patients with seasonal AR. Oralair™, a SLIT tablet containing freeze-dried allergen extracts of five grasses [cocksfoot (Dactylis glomerata), meadow grass (Poa pratensis), rye grass (Lolium perenne), sweet vernal grass (Anthoxanthum odoratum) and timothy grass (Phleum pratense)], and Grazax™, a SLIT tablet containing a standardized extract of grass pollen allergen from timothy grass (P pratenase), are two such agents currently available in many countries. However, head-to-head comparative data are not available. In this study, an indirect comparison on efficacy, safety and cost was undertaken between Oralair™, Grazax™ and SCIT.
A systematic review was conducted for double-blind placebo-controlled randomized trials evaluating Oralair™, Grazax™ or SCIT in patients with grass-induced seasonal AR. Using placebo as the common control, an indirect statistical comparison between treatments was performed using meta regression analysis with active drug as the primary independent variable. An economic analysis, which included both direct and indirect costs for the Canadian setting, was also undertaken.
Overall, 20 placebo-controlled trials met the study inclusion criteria. The indirect analysis suggested improved efficacy with Oralair™ over SCIT [standardized mean difference (SMD) in AR symptom control = -0.21; P = 0.007] and Grazax™ (SMD = -0.18; P = 0.018). In addition, there were no significant differences in the risk of discontinuation due to adverse events between therapies. Oralair™ was associated with cost savings against year-round SCIT ($2471), seasonal SCIT ($948) and Grazax™ ($1168) during the first year of therapy.
Oralair™ has at least non-inferior efficacy and comparable safety against SCIT and Grazax™ at a lower annual cost.
Journal of Evaluation in Clinical Practice 01/2014; 20(3). DOI:10.1111/jep.12112 · 1.08 Impact Factor
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