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Ulrich Wahn - One of the best experts on this subject based on the ideXlab platform.
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five grass pollen sublingual immunotherapy tablet for the treatment of grass pollen induced allergic Rhinoconjunctivitis 5 years of experience
Expert Review of Clinical Immunology, 2014Co-Authors: Alard Didier, Ulrich Wahn, Friedrich Horak, Linda CoxAbstract:Oralair(®) (OA) (Stallergenes, Antony, France) is a unique pre- and co-seasonal 5-grass-pollen sublingual immunotherapy tablet launched in 2008, and now approved in 31 countries worldwide for the treatment of grass-pollen allergic rhinitis and Rhinoconjunctivitis. OA is the first oral treatment with a consistent, well-balanced allergen extract that mimics natural exposure and sensitization. A wealth of data exists from over 5 years of clinical and real-world experience demonstrating the efficacy and safety of OA for grass-pollen-allergy treatment. OA is highly effective from the first pollen season in all patient subgroups, including children and those with comorbid mild asthma, irrespective of sensitization status and symptom severity. OA also has sustained long-term benefits for symptom control and quality of life. This article provides an overview of the pharmacodynamics and pharmacology of OA; its efficacy, safety, tolerability and cost-effectiveness for the treatment of allergic rhinitis and Rhinoconjunctivitis and its role in clinical practice.
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high dose sublingual immunotherapy with single dose aqueous grass pollen extract in children is effective and safe a double blind placebo controlled study
The Journal of Allergy and Clinical Immunology, 2012Co-Authors: Ulrich Wahn, Peter Eberle, L Klimek, Anna Ploszczuk, Thomas Adelt, Bernhard Sandner, Ewa Trebaspietras, Albrecht BufeAbstract:Background Sublingual allergen-specific immunotherapy is a viable alternative to subcutaneous immunotherapy particularly attractive for use in children. Objective This study investigated efficacy and safety of high-dose sublingual immunotherapy (SLIT) in children allergic to grass pollen in a randomized, double-blind, placebo-controlled trial. Methods After a baseline seasonal observation, 207 children aged 4 to 12 years with grass pollen-allergic rhinitis/Rhinoconjunctivitis with/without bronchial asthma (Global Initiative for Asthma I/II) received either high-dose grass pollen SLIT or placebo daily for 1 pre-/co-seasonal period. The primary end point was the change of the area under the curve of the symptom-medication score (SMS) from the baseline season to the first season after start of treatment. Secondary outcomes were well days, responders, immunologic changes, and safety. Results Mean changes in the area under the curve of the SMS from the baseline to the first grass pollen season after the start of treatment were −212.5 for the active group and −97.8 for the placebo group ( P = .0040). Rhinoconjunctivitis SMS ( P = .0020) and separated symptom and medication scores were also statistically different between the 2 groups ( P = .0121 and P = .0226, respectively). The number of well days and the percentage of responders were greater in the active group. Changes in allergen-specific IgE and IgG levels indicated a significant immunologic effect. The treatment was well tolerated, and no serious treatment-related events were reported. Conclusions This study confirmed that this SLIT preparation significantly reduced symptoms and medication use in children with grass pollen–allergic Rhinoconjunctivitis. The preparation showed significant effects on allergen-specific antibodies, was well tolerated, and appeared to be a valid therapeutic option in children allergic to grass pollen. This trial was registered at www.clinicaltrials.gov as NCT00841256.
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efficacy and safety of 5 grass pollen sublingual immunotherapy tablets in pediatric allergic Rhinoconjunctivitis
The Journal of Allergy and Clinical Immunology, 2009Co-Authors: Ulrich Wahn, Susanne Halken, Armelle Montagut, Olivier Beaumont, Ana Isabel Tabar, Piotr Kuna, Martine Le GallAbstract:Background The efficacy and safety of the 300−index of reactivity (IR) dose of 5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergenes, Antony, France) have been demonstrated for the treatment of hay fever in adults. Objective We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen–related allergic rhinitis. Methods In this multinational, randomized, double-blind, placebo-controlled study, 278 children (5–17 years of age) with grass pollen–related Rhinoconjunctivitis (confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement) received once-daily SLIT tablets or placebo. Treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was the Rhinoconjunctivitis total symptom score (RTSS), a sum of 6 individual symptom scores: sneezing, runny nose, itchy nose, nasal congestion, watery eyes, and itchy eyes. Secondary end points included rescue medication intake, individual scores, and safety. Results The intent-to-treat population included 266 children (mean age, 10.9 ± 3.22 years). The RTSS for the 300-IR group was highly significantly different from that of the placebo group ( P = .001). The 300-IR group showed a mean improvement for the RTSS of 28.0% over that seen with placebo and a median improvement of 39.3%. Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season ( P = .0064 and P = .0146, respectively). Adverse events were generally mild or moderate in intensity and expected. No serious side effects were reported. Conclusion Five-grass-pollen SLIT tablets (300 IR) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen–related Rhinoconjunctivitis.
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specific immunotherapy has long term preventive effect of seasonal and perennial asthma 10 year follow up on the pat study
Allergy, 2007Co-Authors: L Jacobsen, Erkka Valovirta, Bodo Niggemann, S Dreborg, Hosne Ara Ferdousi, S Halken, A Host, Antti Koivikko, L A Norberg, Ulrich WahnAbstract:Background: 3-year subcutaneous specific immunotherapy (SIT) in children with seasonal allergic Rhinoconjunctivitis reduced the risk of developing asthma during treatment and 2 years after discontinuation of SIT (5-year follow-up) indicating long-term preventive effect of SIT. Objective: We evaluated the long-term clinical effect and the preventive effect of developing asthma 7-years after termination of SIT. Methods: One hundred and forty-seven subjects, aged 16–25 years with grass and/or birch pollen allergy was investigated 10 years after initiation of a 3-year course of SIT with standardized allergen extracts of grass and/or birch or no SIT respectively. Conjunctival provocations were performed outside the season and methacholine bronchial provocations were performed during the season and winter. Asthma was assessed by clinical evaluation. Results: The significant improvements in Rhinoconjunctivitis and conjunctival sensitivity persisted at the 10-year follow-up. Significantly less actively treated subjects had developed asthma at 10-year follow-up as evaluated by clinical symptoms [odds ratio 2.5 (1.1–5.9)]. Patients who developed asthma among controls were 24/53 and in the SIT group 16/64. The longitudinal treatment effect when adjusted for bronchial hyper-responsiveness and asthma status at baseline including all observations at 3, 5 and 10 years follow-up (children with or without asthma at baseline, n = 189; 511 observations) was statistically significant (P = 0.0075). The odds ratio for no-asthma was 4.6 95% CI (1.5– 13.7) in favor of SIT. Conclusion: A 3-year course of SIT with standardized allergen extracts has shown long-term clinical effects and the potential of preventing development of asthma in children with allergic Rhinoconjunctivitis up to 7 years after treatment. Clinical implication: Specific immunotherapy has long-term clinical effects and the potential of preventing development of asthma in children with allergic rhino conjunctivitis up to 7 years after treatment termination.
Alard Didier - One of the best experts on this subject based on the ideXlab platform.
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five grass pollen sublingual immunotherapy tablet for the treatment of grass pollen induced allergic Rhinoconjunctivitis 5 years of experience
Expert Review of Clinical Immunology, 2014Co-Authors: Alard Didier, Ulrich Wahn, Friedrich Horak, Linda CoxAbstract:Oralair(®) (OA) (Stallergenes, Antony, France) is a unique pre- and co-seasonal 5-grass-pollen sublingual immunotherapy tablet launched in 2008, and now approved in 31 countries worldwide for the treatment of grass-pollen allergic rhinitis and Rhinoconjunctivitis. OA is the first oral treatment with a consistent, well-balanced allergen extract that mimics natural exposure and sensitization. A wealth of data exists from over 5 years of clinical and real-world experience demonstrating the efficacy and safety of OA for grass-pollen-allergy treatment. OA is highly effective from the first pollen season in all patient subgroups, including children and those with comorbid mild asthma, irrespective of sensitization status and symptom severity. OA also has sustained long-term benefits for symptom control and quality of life. This article provides an overview of the pharmacodynamics and pharmacology of OA; its efficacy, safety, tolerability and cost-effectiveness for the treatment of allergic rhinitis and Rhinoconjunctivitis and its role in clinical practice.
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post treatment efficacy of discontinuous treatment with 300ir 5 grass pollen sublingual tablet in adults with grass pollen induced allergic Rhinoconjunctivitis
Clinical & Experimental Allergy, 2013Co-Authors: Alard Didier, Michel Melac, Hans-jørgen Malling, S Soulie, Margitta Worm, Gordon Sussman, Friedrich Horak, Robert K. ZeldinAbstract:BACKGROUND: Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic Rhinoconjunctivitis. OBJECTIVE: To assess the efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet during the post-treatment pollen season of this long-term study. METHODS: Adults aged 18-50, sensitized to grass pollen, with a history of allergic Rhinoconjunctivitis for more than two pollen seasons, and a retrospective Rhinoconjunctivitis total symptom score ≥ 12 (0-18 scale), were randomized to receive Placebo or a 300IR tablet daily beginning either 4 months (4M) or 2 months (2M) prior to each pollen season and continuing for its duration for three consecutive years. They were followed over the subsequent immunotherapy-free pollen season. Post-treatment efficacy was evaluated using the Average Adjusted Symptom Score (AAdSS, adjusting the Rhinoconjunctivitis Total Symptom Score for rescue medication usage) during the post-treatment pollen period. Secondary endpoints included Average Rhinoconjunctivitis Total Symptom Score (ARTSS), Average Rescue Medication Score (ARMS), overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score and safety evaluation. Efficacy variables were analysed using ancova. RESULTS: Overall, 435 patients contributed to the Year 4 efficacy analyses. The Least-Squares (LS) mean differences (95% confidence interval) in AAdSS between active treatment and Placebo over the fourth pollen period were -1.14 (-2.03; -0.26) (P = 0.0114) and -1.43 (-2.32; -0.53) (P = 0.0019) in the (4M) and (2M) groups, corresponding to -22.9% and -28.5% relative LS mean differences (vs. Placebo) respectively. The active groups also showed statistically significant differences compared to Placebo in ARTSS, ARMS and overall RQLQ score. No safety risk was identified during the post-treatment period. CONCLUSIONS AND CLINICAL RELEVANCE: Pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet administered discontinuously for three consecutive years is efficacious post-treatment, safe and well tolerated. Benefits of treatment were meaningful to patients.
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agreement of efficacy assessments for five grass pollen sublingual tablet immunotherapy
Allergy, 2009Co-Authors: Alard Didier, Michel Melac, Armelle Montagut, Ana Isabel Tabar, M Lheritierbarrand, Margitta WormAbstract:Background: The optimal dose of five-grass pollen sublingual tablet immunotherapy (SLIT) was established recently by the primary criteria Rhinoconjunctivitis Total Symptom Score (RTSS) from the first treatment season. Secondary and exploratory criteria, such as RTSS at peak pollen season, exploratory combined symptom and rescue medication use score, quality of life and immunological markers are calculated and described in this analysis. Methods: Six hundred and twenty-eight patients with grass pollen Rhinoconjunctivitis (≥2 years duration) were randomized in a double-blind, placebo-controlled trial conducted in Europe. Patients received once-daily SLIT (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before grass pollen season and throughout the 2005 season. Patients were instructed to take rescue medication only if symptoms were severe and record symptom severity on using the RTSS. Results: Both 300IR and 500IR doses significantly reduced mean RTSS at pollen peak (P = 0.0005 and P = 0.0014, respectively) and the exploratory combined score (P = 0.0001 and P = 0.0026, respectively) compared with placebo. Compared with patients in the placebo group, those who were taking the 300IR and 500IR doses reported significantly improved quality of life using the mean Rhinoconjunctivitis Quality of Life Questionnaire scores during the peak of the pollen season (P < 0.0001) and at the end of the pollen season (P = 0.0031 and P ≤ 0.0001, respectively). Specific immunoglobulin G4 increased significantly depending on the SLIT dose (P < 0.0001). Conclusions: All secondary efficacy criteria, including efficacy at pollen peak, combined score, quality of life and immunological changes, indicate that 300IR tablets represent the optimal dose and suggest it is appropriate for use in clinical practice.
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optimal dose efficacy and safety of once daily sublingual immunotherapy with a 5 grass pollen tablet for seasonal allergic rhinitis
The Journal of Allergy and Clinical Immunology, 2007Co-Authors: Alard Didier, Hans-jørgen Malling, Armelle Montagut, Olivier Beaumont, Margitta Worm, Friedrich Horak, Siegfried Jager, Claude Andre, Michel MelacAbstract:Background Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults, but it lacks optimum dose definition. Objective To assess the efficacy, safety, and optimal dose of grass pollen tablets for immunotherapy of patients with allergic Rhinoconjunctivitis. Methods In this multinational, randomized, double-blind, placebo-controlled study, 628 adults with grass pollen Rhinoconjunctivitis (confirmed by positive skin prick test and serum-specific IgE) received 1 of 3 doses of a standardized 5–grass pollen extract, or placebo, administered sublingually using a once-daily tablet formulation. The treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was Rhinoconjunctivitis Total Symptom Score; secondary outcomes included 6 individual symptom scores, rescue medication use, quality of life, and safety assessments. Results Both the 300–index of reactivity (IR) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score (3.58 ± 3.0, P = .0001; and 3.74 ± 3.1, P = .0006, respectively) compared with placebo (4.93 ± 3.2) in the intent-to-treat and per-protocol analyses. The 100-IR group (4.70 ± 3.1) score was not significantly different from placebo. Analysis of all secondary efficacy variables (sneezing, runny nose, itchy nose, nasal congestion, watery eyes, itchy eyes, rescue medication usage, and quality of life) confirmed the efficacy of the 300-IR and 500-IR doses. No serious side effects were reported. Conclusion In the first pollen season, the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed. The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo. Clinical implications The risk-benefit ratio favors the use of 300-IR tablets for clinical practice.
Hans-jørgen Malling - One of the best experts on this subject based on the ideXlab platform.
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recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic Rhinoconjunctivitis an eaaci position paper
Allergy, 2014Co-Authors: Oliver Pfaar, Hans-jørgen Malling, Gerth R. Van Wijk, Stephen R Durham, P Demoly, Jean Bousquet, Giorgio Walter Canonica, S Bonini, Lars Jacobsen, R MosgesAbstract:Background Allergen immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic Rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. Methods As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic Rhinoconjunctivitis. Results Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. Conclusion A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic Rhinoconjunctivitis.
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sustained efficacy and safety of a 300ir daily dose of a sublingual solution of birch pollen allergen extract in adults with allergic Rhinoconjunctivitis results of a double blind placebo controlled study
Clinical and Translational Allergy, 2014Co-Authors: Margitta Worm, Michel Melac, Hans-jørgen Malling, Frederic De Blay, Veronique Cadic, Robert K. ZeldinAbstract:Background 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.
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post treatment efficacy of discontinuous treatment with 300ir 5 grass pollen sublingual tablet in adults with grass pollen induced allergic Rhinoconjunctivitis
Clinical & Experimental Allergy, 2013Co-Authors: Alard Didier, Michel Melac, Hans-jørgen Malling, S Soulie, Margitta Worm, Gordon Sussman, Friedrich Horak, Robert K. ZeldinAbstract:BACKGROUND: Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic Rhinoconjunctivitis. OBJECTIVE: To assess the efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet during the post-treatment pollen season of this long-term study. METHODS: Adults aged 18-50, sensitized to grass pollen, with a history of allergic Rhinoconjunctivitis for more than two pollen seasons, and a retrospective Rhinoconjunctivitis total symptom score ≥ 12 (0-18 scale), were randomized to receive Placebo or a 300IR tablet daily beginning either 4 months (4M) or 2 months (2M) prior to each pollen season and continuing for its duration for three consecutive years. They were followed over the subsequent immunotherapy-free pollen season. Post-treatment efficacy was evaluated using the Average Adjusted Symptom Score (AAdSS, adjusting the Rhinoconjunctivitis Total Symptom Score for rescue medication usage) during the post-treatment pollen period. Secondary endpoints included Average Rhinoconjunctivitis Total Symptom Score (ARTSS), Average Rescue Medication Score (ARMS), overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score and safety evaluation. Efficacy variables were analysed using ancova. RESULTS: Overall, 435 patients contributed to the Year 4 efficacy analyses. The Least-Squares (LS) mean differences (95% confidence interval) in AAdSS between active treatment and Placebo over the fourth pollen period were -1.14 (-2.03; -0.26) (P = 0.0114) and -1.43 (-2.32; -0.53) (P = 0.0019) in the (4M) and (2M) groups, corresponding to -22.9% and -28.5% relative LS mean differences (vs. Placebo) respectively. The active groups also showed statistically significant differences compared to Placebo in ARTSS, ARMS and overall RQLQ score. No safety risk was identified during the post-treatment period. CONCLUSIONS AND CLINICAL RELEVANCE: Pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet administered discontinuously for three consecutive years is efficacious post-treatment, safe and well tolerated. Benefits of treatment were meaningful to patients.
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optimal dose efficacy and safety of once daily sublingual immunotherapy with a 5 grass pollen tablet for seasonal allergic rhinitis
The Journal of Allergy and Clinical Immunology, 2007Co-Authors: Alard Didier, Hans-jørgen Malling, Armelle Montagut, Olivier Beaumont, Margitta Worm, Friedrich Horak, Siegfried Jager, Claude Andre, Michel MelacAbstract:Background Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults, but it lacks optimum dose definition. Objective To assess the efficacy, safety, and optimal dose of grass pollen tablets for immunotherapy of patients with allergic Rhinoconjunctivitis. Methods In this multinational, randomized, double-blind, placebo-controlled study, 628 adults with grass pollen Rhinoconjunctivitis (confirmed by positive skin prick test and serum-specific IgE) received 1 of 3 doses of a standardized 5–grass pollen extract, or placebo, administered sublingually using a once-daily tablet formulation. The treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was Rhinoconjunctivitis Total Symptom Score; secondary outcomes included 6 individual symptom scores, rescue medication use, quality of life, and safety assessments. Results Both the 300–index of reactivity (IR) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score (3.58 ± 3.0, P = .0001; and 3.74 ± 3.1, P = .0006, respectively) compared with placebo (4.93 ± 3.2) in the intent-to-treat and per-protocol analyses. The 100-IR group (4.70 ± 3.1) score was not significantly different from placebo. Analysis of all secondary efficacy variables (sneezing, runny nose, itchy nose, nasal congestion, watery eyes, itchy eyes, rescue medication usage, and quality of life) confirmed the efficacy of the 300-IR and 500-IR doses. No serious side effects were reported. Conclusion In the first pollen season, the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed. The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo. Clinical implications The risk-benefit ratio favors the use of 300-IR tablets for clinical practice.
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the safety and efficacy of subcutaneous birch pollen immunotherapy a one year randomised double blind placebo controlled study
Allergy, 2002Co-Authors: Uffe Bodtger, Lars K Poulsen, Henrik H Jacobi, Hans-jørgen MallingAbstract:Background: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America. Methods: Thirty-five patients with severe Rhinoconjunctivitis (hay fever) to birch pollen were allocated to double-blinded clustered IT with a depot birch pollen extract (Betula verrucosa) or placebo injections. Seven patients in each group had concomitant self-reported seasonal asthma. Treatment was conducted as a clustered regimen and was performed in a specialist unit. Symptom scores from nose, eyes, and lungs, and use of oral and topical antihistamines, beta-2-agonists, and oral corticosteroids were recorded daily during the season of 2000. Sensitivity to allergen provocation in skin, conjunctiva, and nasal mucosa was measured before and after 10 months of treatment. Post-seasonal assessment of symptom severity was performed using a simple questionnaire. Results: IT reduced the symptom score for both Rhinoconjunctivitis and asthma (P-values < 0.05), total medication score (P < 0.02) and use of oral antihistamines (P < 0.01). IT reduced specific conjunctival sensitivity (P < 0.05), skin prick test, and especially cutaneous late-phase response diameters (P < 0.00001), and increased general well-being on post-seasonal evaluation (P < 0.01). IT was safe, with side-effects at the same level as placebo. Conclusions: High-dose, subcutaneous IT is efficacious and safe in patients with severe birch pollen Rhinoconjunctivitis and asthma.
Michel Melac - One of the best experts on this subject based on the ideXlab platform.
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sustained efficacy and safety of a 300ir daily dose of a sublingual solution of birch pollen allergen extract in adults with allergic Rhinoconjunctivitis results of a double blind placebo controlled study
Clinical and Translational Allergy, 2014Co-Authors: Margitta Worm, Michel Melac, Hans-jørgen Malling, Frederic De Blay, Veronique Cadic, Robert K. ZeldinAbstract:Background 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.
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post treatment efficacy of discontinuous treatment with 300ir 5 grass pollen sublingual tablet in adults with grass pollen induced allergic Rhinoconjunctivitis
Clinical & Experimental Allergy, 2013Co-Authors: Alard Didier, Michel Melac, Hans-jørgen Malling, S Soulie, Margitta Worm, Gordon Sussman, Friedrich Horak, Robert K. ZeldinAbstract:BACKGROUND: Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic Rhinoconjunctivitis. OBJECTIVE: To assess the efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet during the post-treatment pollen season of this long-term study. METHODS: Adults aged 18-50, sensitized to grass pollen, with a history of allergic Rhinoconjunctivitis for more than two pollen seasons, and a retrospective Rhinoconjunctivitis total symptom score ≥ 12 (0-18 scale), were randomized to receive Placebo or a 300IR tablet daily beginning either 4 months (4M) or 2 months (2M) prior to each pollen season and continuing for its duration for three consecutive years. They were followed over the subsequent immunotherapy-free pollen season. Post-treatment efficacy was evaluated using the Average Adjusted Symptom Score (AAdSS, adjusting the Rhinoconjunctivitis Total Symptom Score for rescue medication usage) during the post-treatment pollen period. Secondary endpoints included Average Rhinoconjunctivitis Total Symptom Score (ARTSS), Average Rescue Medication Score (ARMS), overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score and safety evaluation. Efficacy variables were analysed using ancova. RESULTS: Overall, 435 patients contributed to the Year 4 efficacy analyses. The Least-Squares (LS) mean differences (95% confidence interval) in AAdSS between active treatment and Placebo over the fourth pollen period were -1.14 (-2.03; -0.26) (P = 0.0114) and -1.43 (-2.32; -0.53) (P = 0.0019) in the (4M) and (2M) groups, corresponding to -22.9% and -28.5% relative LS mean differences (vs. Placebo) respectively. The active groups also showed statistically significant differences compared to Placebo in ARTSS, ARMS and overall RQLQ score. No safety risk was identified during the post-treatment period. CONCLUSIONS AND CLINICAL RELEVANCE: Pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet administered discontinuously for three consecutive years is efficacious post-treatment, safe and well tolerated. Benefits of treatment were meaningful to patients.
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early onset of action of a 5 grass pollen 300 ir sublingual immunotherapy tablet evaluated in an allergen challenge chamber
The Journal of Allergy and Clinical Immunology, 2009Co-Authors: Friedrich Horak, Michel Melac, Armelle Montagut, Philippe Devillier, Petra Zieglmayer, Rene Zieglmayer, Patrick Lemell, S Galvain, Stephanie Jeanalphonse, Laurence Van OvertveltAbstract:Background The efficacy and safety of a 5-grass-pollen sublingual immunotherapy (SLIT) tablet (Stallergenes SA, Antony, France) have been evaluated in clinical studies during the pollen season. The allergen challenge chamber (ACC) has been developed as a pharmacodynamic assessment tool to control the environmental allergens and to avoid all problems associated with unpredictable pollen seasons. Objective We sought to evaluate the onset of action and efficacy of 300-IR (index of reactivity) SLIT tablets by using an ACC. Methods Patients with grass pollen–induced Rhinoconjunctivitis were randomized into the active or placebo groups. A standardized allergen challenge with grass pollen and symptom evaluation every 15 minutes was performed at baseline, 1 week, and 1, 2, and 4 months of treatment. The primary end point was the average Rhinoconjunctivitis total symptom score (ARTSS). Allergen-specific basophil activation, T-cell proliferation, and plasmatic IgE and IgG responses were assessed before and after treatment. Results In the intention-to-treat population (n = 89) a significant treatment effect was achieved after the first month ( P = .0042) and second month ( P = .0203) and was maintained through to the fourth month ( P = .0007). In the active group the ARTSS (means ± SDs) decreased at each challenge: week 1, 7.40 ± 2.682; month 1, 5.89 ± 2.431; month 2, 5.09 ± 2.088; and month 4, 4.85 ± 1.999. An improvement (vs placebo) of 29.3% for the mean ARTSS (median, 33.3%) was observed at end point. Furthermore, the induction of grass pollen allergen–specific IgGs was associated with clinical response. The most frequent adverse reactions were local: oral pruritus, ear pruritus, and throat irritation. Conclusions In this ACC study the 300-IR 5-grass-pollen SLIT tablets had a significant effect on Rhinoconjunctivitis symptoms (vs placebo) from the first month of treatment onward.
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agreement of efficacy assessments for five grass pollen sublingual tablet immunotherapy
Allergy, 2009Co-Authors: Alard Didier, Michel Melac, Armelle Montagut, Ana Isabel Tabar, M Lheritierbarrand, Margitta WormAbstract:Background: The optimal dose of five-grass pollen sublingual tablet immunotherapy (SLIT) was established recently by the primary criteria Rhinoconjunctivitis Total Symptom Score (RTSS) from the first treatment season. Secondary and exploratory criteria, such as RTSS at peak pollen season, exploratory combined symptom and rescue medication use score, quality of life and immunological markers are calculated and described in this analysis. Methods: Six hundred and twenty-eight patients with grass pollen Rhinoconjunctivitis (≥2 years duration) were randomized in a double-blind, placebo-controlled trial conducted in Europe. Patients received once-daily SLIT (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before grass pollen season and throughout the 2005 season. Patients were instructed to take rescue medication only if symptoms were severe and record symptom severity on using the RTSS. Results: Both 300IR and 500IR doses significantly reduced mean RTSS at pollen peak (P = 0.0005 and P = 0.0014, respectively) and the exploratory combined score (P = 0.0001 and P = 0.0026, respectively) compared with placebo. Compared with patients in the placebo group, those who were taking the 300IR and 500IR doses reported significantly improved quality of life using the mean Rhinoconjunctivitis Quality of Life Questionnaire scores during the peak of the pollen season (P < 0.0001) and at the end of the pollen season (P = 0.0031 and P ≤ 0.0001, respectively). Specific immunoglobulin G4 increased significantly depending on the SLIT dose (P < 0.0001). Conclusions: All secondary efficacy criteria, including efficacy at pollen peak, combined score, quality of life and immunological changes, indicate that 300IR tablets represent the optimal dose and suggest it is appropriate for use in clinical practice.
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optimal dose efficacy and safety of once daily sublingual immunotherapy with a 5 grass pollen tablet for seasonal allergic rhinitis
The Journal of Allergy and Clinical Immunology, 2007Co-Authors: Alard Didier, Hans-jørgen Malling, Armelle Montagut, Olivier Beaumont, Margitta Worm, Friedrich Horak, Siegfried Jager, Claude Andre, Michel MelacAbstract:Background Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults, but it lacks optimum dose definition. Objective To assess the efficacy, safety, and optimal dose of grass pollen tablets for immunotherapy of patients with allergic Rhinoconjunctivitis. Methods In this multinational, randomized, double-blind, placebo-controlled study, 628 adults with grass pollen Rhinoconjunctivitis (confirmed by positive skin prick test and serum-specific IgE) received 1 of 3 doses of a standardized 5–grass pollen extract, or placebo, administered sublingually using a once-daily tablet formulation. The treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was Rhinoconjunctivitis Total Symptom Score; secondary outcomes included 6 individual symptom scores, rescue medication use, quality of life, and safety assessments. Results Both the 300–index of reactivity (IR) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score (3.58 ± 3.0, P = .0001; and 3.74 ± 3.1, P = .0006, respectively) compared with placebo (4.93 ± 3.2) in the intent-to-treat and per-protocol analyses. The 100-IR group (4.70 ± 3.1) score was not significantly different from placebo. Analysis of all secondary efficacy variables (sneezing, runny nose, itchy nose, nasal congestion, watery eyes, itchy eyes, rescue medication usage, and quality of life) confirmed the efficacy of the 300-IR and 500-IR doses. No serious side effects were reported. Conclusion In the first pollen season, the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed. The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo. Clinical implications The risk-benefit ratio favors the use of 300-IR tablets for clinical practice.
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recommendations for the standardization of clinical outcomes used in allergen immunotherapy trials for allergic Rhinoconjunctivitis an eaaci position paper
Allergy, 2014Co-Authors: Oliver Pfaar, Hans-jørgen Malling, Gerth R. Van Wijk, Stephen R Durham, P Demoly, Jean Bousquet, Giorgio Walter Canonica, S Bonini, Lars Jacobsen, R MosgesAbstract:Background Allergen immunotherapy (AIT) has been thoroughly documented in randomized controlled trials (RCTs). It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic Rhinoconjunctivitis, allergic asthma and insect sting allergy. However, there is a high degree of clinical and methodological heterogeneity among the endpoints in clinical studies on AIT, for both subcutaneous and sublingual immunotherapy (SCIT and SLIT). At present, there are no commonly accepted standards for defining the optimal outcome parameters to be used for both primary and secondary endpoints. Methods As elaborated by a Task Force (TF) of the European Academy of Allergy and Clinical Immunology (EAACI) Immunotherapy Interest Group, this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic Rhinoconjunctivitis. Results Based on a thorough literature review, the TF members have outlined recommendations for nine domains of clinical outcome measures. As the primary outcome, the TF recommends a homogeneous combined symptom and medication score (CSMS) as a simple and standardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner. All outcomes, grouped into nine domains, are reviewed. Conclusion A standardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required. The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic Rhinoconjunctivitis.
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sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years
The Journal of Allergy and Clinical Immunology, 2008Co-Authors: Ronald Dahl, W Emminger, Bente Riis, Jan G.r. De Monchy, Alexander Kapp, Sabina Rak, G L Colombo, Pernille Milvang Gronager, Stephen R DurhamAbstract: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-Abello A/S, Horsholm, 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 Conclusion Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment.
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efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic Rhinoconjunctivitis
The Journal of Allergy and Clinical Immunology, 2006Co-Authors: Ronald Dahl, W Emminger, Jan G.r. De Monchy, Alexander Kapp, Sabina Rak, G L Colombo, Montserrat Fernandez Rivas, Mette Ribel, Stephen R DurhamAbstract: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-Abello, Horsholm, 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 P 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.
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sublingual immunotherapy with once daily grass allergen tablets a randomized controlled trial in seasonal allergic Rhinoconjunctivitis
The Journal of Allergy and Clinical Immunology, 2006Co-Authors: Stephen R Durham, William H Yang, Martin R Pedersen, Niels Johansen, Sabina RakAbstract:Background Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases. Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events. Objective To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic Rhinoconjunctivitis. Methods A multinational, multicenter, randomized, placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen–induced allergic Rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX; ALK-Abello, Horsholm, Denmark) or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks. Results Average Rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T ( P = .0710; P = .0470) compared with placebo. Significantly better Rhinoconjunctivitis quality of life scores ( P = .006) and an increased number of well days ( P = .041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication use, 29%, P = .0120). No safety concerns were observed. Conclusion This study confirms dose-dependent efficacy of the grass allergen tablet. Although further studies are required, the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy. Clinical implications For patients with grass pollen allergy, sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life.
