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      Health economic comparison of SLIT allergen and SCIT allergoid immunotherapy in patients with seasonal grass-allergic rhinoconjunctivitis in Germany

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          Abstract

          Background

          Allergoids are chemically modified allergen extracts administered to reduce allergenicity and to maintain immunogenicity. Oralair® (the 5-grass tablet) is a sublingual native grass allergen tablet for pre- and co-seasonal treatment. Based on a literature review, meta-analysis, and cost-effectiveness analysis the relative effects and costs of the 5-grass tablet versus a mix of subcutaneous allergoid compounds for grass pollen allergic rhinoconjunctivitis were assessed.

          Methods

          A Markov model with a time horizon of nine years was used to assess the costs and effects of three-year immunotherapy treatment. Relative efficacy expressed as standardized mean differences was estimated using an indirect comparison on symptom scores extracted from available clinical trials. The Rhinitis Symptom Utility Index (RSUI) was applied as a proxy to estimate utility values for symptom scores. Drug acquisition and other medical costs were derived from published sources as well as estimates for resource use, immunotherapy persistence, and occurrence of asthma. The analysis was executed from the German payer’s perspective, which includes payments of the Statutory Health Insurance (SHI) and additional payments by insurants. Comprehensive deterministic and probabilistic sensitivity analyses and different scenarios were performed to test the uncertainty concerning the incremental model outcomes.

          Results

          The applied model predicted a cost-utility ratio of the 5-grass tablet versus a market mix of injectable allergoid products of € 12,593 per QALY in the base case analysis. Predicted incremental costs and QALYs were € 458 (95% confidence interval, CI: € 220; € 739) and 0.036 (95% CI: 0.002; 0.078), respectively. Compared to the allergoid mix the probability of the 5-grass tablet being the most cost-effective treatment option was predicted to be 76% at a willingness-to-pay threshold of € 20,000. The results were most sensitive to changes in efficacy estimates, duration of the pollen season, and immunotherapy persistence rates.

          Conclusions

          This analysis suggests the sublingual native 5-grass tablet to be cost-effective relative to a mix of subcutaneous allergoid compounds. The robustness of these statements has been confirmed in extensive sensitivity and scenario analyses.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s13601-015-0045-z) contains supplementary material, which is available to authorized users.

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          Most cited references45

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          Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study.

          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. We evaluated the long-term clinical effect and the preventive effect of developing asthma 7-years after termination of SIT. 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. 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. 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. 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.
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            Allergic Rhinitis and its Impact on Asthma (ARIA): Achievements in 10 years and future needs

            Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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              Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis.

              Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults, but it lacks optimum dose definition. To assess the efficacy, safety, and optimal dose of grass pollen tablets for immunotherapy of patients with allergic rhinoconjunctivitis. 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. 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. 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. The risk-benefit ratio favors the use of 300-IR tablets for clinical practice.
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                Author and article information

                Contributors
                bverheggen@pharmerit.com
                kwesterhout@pharmerit.com
                HSchreder@stallergenes.de
                m.augustin@uke.de
                Journal
                Clin Transl Allergy
                Clin Transl Allergy
                Clinical and Translational Allergy
                BioMed Central (London )
                2045-7022
                21 January 2015
                21 January 2015
                2015
                : 5
                : 1
                Affiliations
                [ ]Pharmerit International, Marten Meesweg, 107 3068AV Rotterdam, The Netherlands
                [ ]Stallergenes GmbH, Kamp-Lintfort, Germany
                [ ]University Medical Center and Hamburg Center for Health Economics, Hamburg, Germany
                Article
                45
                10.1186/s13601-015-0045-z
                4330981
                fe8cc641-4794-4eee-90bd-ecf4425d39c6
                © Verheggen et al.; licensee BioMed Central. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 6 May 2014
                : 2 January 2015
                Categories
                Research
                Custom metadata
                © The Author(s) 2015

                Immunology
                Immunology

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