A non-stationary Markov model for economic evaluation of grass pollen allergoid immunotherapy.

INTRODUCTION: Allergic rhino-conjunctivitis (ARC) is an IgE-mediated disease that occurs after exposure to indoor or outdoor allergens, or to non-specific triggers. Effective treatment options for seasonal ARC are available, but the economic aspects and burden of these therapies are not of secondary importance, also considered that the prevalence of ARC has been estimated at 23% in Europe. For these reasons, we propose a novel flexible cost-effectiveness analysis (CEA) model, intended to provide healthcare professionals and policymakers with useful information aimed at cost-effective interventions for grass-pollen induced allergic rhino-conjunctivitis (ARC). METHODS: Treatments compared are: 1. no AIT, first-line symptomatic drug-therapy with no allergoid immunotherapy (AIT). 2. SCIT, subcutaneous immunotherapy. 3. SLIT, sublingual immunotherapy. The proposed model is a non-stationary Markovian model, that is flexible enough to reflect those treatment-related problems often encountered in real-life and clinical practice, but that cannot be adequately represented in randomized clinical trials (RCTs). At the same time, we described in detail all the structural elements of the model as well as its input parameters, in order to minimize any issue of transparency and facilitate the reproducibility and circulation of the results among researchers. RESULTS: Using the no AIT strategy as a comparator, and the Incremental Cost Effectiveness Ratio (ICER) as a statistic to summarize the cost-effectiveness of a health care intervention, we could conclude that: SCIT systematically outperforms SLIT, except when a full societal perspective is considered. For example, for T = 9 and a pollen season of 60 days, we have ICER = €16,729 for SCIT vs. ICER = €15,116 for SLIT (in the full societal perspective).For longer pollen seasons or longer follow-up duration the ICER decreases, because each patient experiences a greater clinical benefit over a larger time span, and Quality-adjusted Life Year (QALYs) gained per cycle increase accordingly.Assuming that no clinical benefit is achieved after premature discontinuation, and that at least three years of immunotherapy are required to improve clinical manifestations and perceiving a better quality of life, ICERs become far greater than €30,000.If the immunotherapy is effective only at the peak of the pollen season, the relative ICERs rise sharply. For example, in the scenario where no clinical benefit is present after premature discontinuation of immunotherapy, we have ICER = €74,770 for SCIT vs. ICER = €152,110 for SLIT.The distance between SCIT and SLIT strongly depends on under which model the interventions are meta-analyzed. CONCLUSIONS: Even though there is a considerable evidence that SCIT outperforms SLIT, we could not state that both SCIT and SLIT (or only one of these two) can be considered cost-effective for ARC, as a reliable threshold value for cost-effectiveness set by national regulatory agencies for pharmaceutical products is missing. Moreover, the impact of model input parameters uncertainty on the reliability of our conclusions needs to be investigated further.

Next generation immunotherapy for tree pollen allergies.

Tree pollen induced allergies are one of the major medical and public health burdens in the industrialized world. Allergen-Specific Immunotherapy (AIT) through subcutaneous injection or sublingual delivery is the only approved therapy with curative potential to pollen induced allergies. AIT often is associated with severe side effects and requires long-term treatment. Safer, more effective and convenient allergen specific immunotherapies remain an unmet need. In this review article, we discuss the current progress in applying protein and peptide-based approaches and DNA vaccines to the clinical challenges posed by tree pollen allergies through the lens of preclinical animal models and clinical trials, with an emphasis on the birch and Japanese red cedar pollen induced allergies.

Molecular diagnosis and immunotherapy.

PURPOSE OF REVIEW: To describe recent insights into how molecular diagnosis can improve indication and selection of suitable allergens for specific immunotherapy and increase the safety of this therapy. RECENT FINDINGS: As specific allergen immunotherapy targets specific allergens, identification of the disease-eliciting allergen is a prerequisite for accurate prescription of treatment. In areas of complex sensitization to aeroallergens or in cases of hymenoptera venom allergy, the use of molecular diagnosis has demonstrated that it may lead to a change in indication and selection of allergens for immunotherapy in a large proportion of patients when compared with diagnosis based on skin prick testing and/or specific IgE determination with commercial extracts. These changes in immunotherapy prescription aided by molecular diagnosis have been demonstrated to be cost-effective in some scenarios. Certain patterns of sensitization to grass or olive pollen and bee allergens may identify patients with higher risk of adverse reaction during immunotherapy. SUMMARY: Molecular diagnosis, when used with other tools and patients' clinical records, can help clinicians better to select the most appropriate patients and allergens for specific immunotherapy and, in some cases, predict the risk of adverse reactions. The pattern of sensitization to allergens could potentially predict the efficacy of allergen immunotherapy provided that these immunotherapy products contain a sufficient amount of these allergens. Nevertheless, multiplex assay remains a third-level approach, not to be used as screening method in current practice.

Comparison of six disease severity scores for allergic rhinitis against pollen counts a prospective analysis at population and individual level.

BACKGROUND: Many different symptom (medication) scores are nowadays used as measures of allergic rhinoconjunctivitis severity in individual patients and in clinical trials. Their differences contribute to the heterogeneity of the primary end-point in meta-analyses, so that calls for symptom (medication) score harmonization have been launched. OBJECTIVE: To prospectively compare six different severity scores for allergic rhinitis (AR) against pollen counts at both population and individual levels. METHODS: Two groups of children with seasonal AR and grass pollen sensitization were recruited in Ascoli, Italy (n = 76) and Berlin, Germany (n = 29). Symptoms and drug intake were monitored daily for 40 and 30 days of the grass pollen season in 2011 (Ascoli) and 2013 (Berlin), respectively, through an Internet-based platform (AllergyMonitor(™) , TPS Production srl, Rome, Italy). From the gathered data, the informatics platform automatically generated one symptom score (RTSS) and five symptom-medication scores (RC-ACS(©) , ACS, RTSS[LOCF], RTSS[WC] and AdSS). Values were then statistically normalized for reciprocal comparison and matched against the daily variations of local grass pollen counts (Spearman's rank correlation). RESULTS: The grass pollen counts were higher in Ascoli than in Berlin (peak values 194 vs. 59 grains/m(3) ). At population level, the trajectories of the normalized average values of the six scores differed only slightly in both studies and correlated well with the pollen counts (ranges r(2) : 0.38-0.50 in Ascoli, 0.41-0.56 in Berlin). By contrast, in individual patients, trajectories of different scores were often quite heterogeneous. The RTSS[WC] had a very low discriminatory power and generated in many patients long, flat horizontal segments. CONCLUSIONS: Disease severity scores for seasonal AR, as evaluated via an Internet-based platform, tend to provide similar results at population level but can often produce heterogeneous slopes in individual patients. The choice of the disease severity score might have only a low impact on the outcome of a very large clinical trial, but it may be crucial in the management of individual patients.

Comparison of outcome measures in allergic rhinitis in children, adolescents and adults.

BACKGROUND: Grass pollen-induced allergic rhinoconjunctivitis (AR) is very common worldwide. However, its symptoms may vary with the patient's age. The present study compared symptom profiles and quality of life (QoL) in children, adolescents and adults with grass pollen-induced AR. METHODS: This was a four-week, multicentre, observational study of children (aged 6-11), adolescents (12-17) and adults (18-65) consulting specialist physicians in France. The management of AR was at the physicians' discretion. Participants regularly rated their symptoms (the rhinoconjunctivitis total symptom score (RTSS) and a visual analogue scale (VAS)) and QoL (the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: A total of 806 patients (253 children, 250 adolescents and 303 adults, of whom 83.5% suffered from moderate-to-severe, persistent AR) provided data for at least the first 2 weeks of the study. Ocular pruritus (the most bothersome symptom in children (35%), adolescents (22%) and adults (16%)) was associated with poor QoL in all groups, whereas nasal obstruction and pruritus were associated with poor QoL in adolescents and children. Over 4 weeks, the weekly mean RTSS and VAS scores fell by around half. This change was associated with an improvement in the RQLQ scores. In all age groups, the VAS score was well correlated with the weekly mean RTSS score (Pearson's r: 0.79-0.88) and moderately correlated with the weekly mean RQLQ score (Pearson's r: 0.64-0.80). CONCLUSIONS: In moderate-to-severe grass pollen-induced AR, symptom perception differs in children vs. older patients. However, the assessments of treatment outcomes (using the RTSS, VAS and RQLQ) were similar in all age groups.

Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. OBJECTIVE: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. METHODS: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. RESULTS: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent. CONCLUSION: Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance.

Assessment of specific immunotherapy efficacy using a novel placebo score-based method.

BACKGROUND: In trials of allergen immunotherapy, allergen exposure is typically assessed by pollen counts, but these may misrepresent exposure if performed remotely from multiple study centers. OBJECTIVE: To assess whether symptomatology in placebo-treated patients is a better measure of local allergen burden at individual centers in such trials. METHODS: Data from a multicenter, placebo-controlled trial of preseasonal grass pollen immunotherapy were reanalyzed to identify the 4 weeks at each center in which the placebo-treated subjects had the highest combined symptom/medication scores (CSMS). The difference in CSMS between active and placebo groups was compared during the 4 peak placebo score weeks (PlSW) and the 4 peak pollen count weeks (PoCW). RESULTS: The benefit of immunotherapy over placebo in the PlSW analysis (18.5%) was greater than in the PoCW analysis (13.6%), with increased statistical significance (P = .0001, .0038, respectively). Similar improved discrimination was observed when analyzing benefits in subgroups of patients with severe symptoms, a high disease burden, and in different geographical locations. CONCLUSION: This novel PlSW analysis results in better discrimination of the effects of allergen immunotherapy compared with placebo and may be widely applicable in similar studies, both prospectively and retrospectively.

Nasal nitric oxide measurements in the assessment of nasal allergen challenge.

BACKGROUND: Several objective methods are used to assess the result of nasal allergen challenge. OBJECTIVE: The aim of this study was to compare the diagnostic value of nasal nitric oxide (nNO) measurements with that of peak nasal inspiratory flow (PNIF), nasal lavage fluid beta-tryptase levels, and changes in cell count after nasal challenge with grass pollen. METHODS: The study population comprised 24 patients allergic to grass pollen and 24 healthy controls. All participants underwent grass allergen challenge preceded by administration of placebo. A visual analog scale was administered. nNO and PNIF were determined, and nasal lavage fluid was collected before and 30 minutes after administration of placebo and allergen. The study was performed outside the pollen season. RESULTS: Significant changes in nNO, PNIF, nasal lavage fluid beta-tryptase level, and cell count were observed only in allergic patients after administration of the allergen. Receiver operating characteristic (ROC) curves were drawn for each determination. A change in nNO levels of -11.987% was indicated as the best cutoff point for differentiating between allergic patients and healthy participants with a sensitivity of 60.9%, specificity of 100%, negative predictive value of 71%, and positive predictive value of 100%. Comparison of the area under the ROC curve did not show significant differences between the diagnostic value of changes in nNO levels and other objective methods of assessing the outcome of the challenge. CONCLUSION: Changes in nNO levels do not differ significantly from other methods used to objectively assess the outcome of nasal challenge. Given their insufficient sensitivity, nNO measurements have limited value as the sole diagnostic tool when assessing the outcome of nasal challenge.

Cost effectiveness analysis of immunotherapy in patients with grass pollen allergic rhinoconjunctivitis in Germany.

OBJECTIVES: An economic evaluation was conducted to assess the outcomes and costs as well as cost-effectiveness of the following grass-pollen immunotherapies: OA (Oralair; Stallergenes S.A., Antony, France) vs GRZ (Grazax; ALK-Abelló, Hørsholm, Denmark), and ALD (Alk Depot SQ; ALK-Abelló) (immunotherapy agents alongside symptomatic medication) and symptomatic treatment alone for grass pollen allergic rhinoconjunctivitis. METHODS: The costs and outcomes of 3-year treatment were assessed for a period of 9 years using a Markov model. Treatment efficacy was estimated using an indirect comparison of available clinical trials with placebo as a common comparator. Estimates for immunotherapy discontinuation, occurrence of asthma, health state utilities, drug costs, resource use, and healthcare costs were derived from published sources. The analysis was conducted from the insurant's perspective including public and private health insurance payments and co-payments by insurants. Outcomes were reported as quality-adjusted life years (QALYs) and symptom-free days. The uncertainty around incremental model results was tested by means of extensive deterministic univariate and probabilistic multivariate sensitivity analyses. RESULTS: In the base case analysis the model predicted a cost-utility ratio of OA vs symptomatic treatment of €14,728 per QALY; incremental costs were €1356 (95%CI: €1230; €1484) and incremental QALYs 0.092 (95%CI: 0.052; 0.140). OA was the dominant strategy compared to GRZ and ALD, with estimated incremental costs of -€1142 (95%CI: -€1255; -€1038) and -€54 (95%CI: -€188; €85) and incremental QALYs of 0.015 (95%CI: -0.025; 0.056) and 0.027 (95%CI: -0.022; 0.075), respectively. At a willingness-to-pay threshold of €20,000, the probability of OA being the most cost-effective treatment was predicted to be 79%. Univariate sensitivity analyses show that incremental outcomes were moderately sensitive to changes in efficacy estimates. The main study limitation was the requirement of an indirect comparison involving several steps to assess relative treatment effects. CONCLUSION: The analysis suggests OA to be cost-effective compared to GRZ and ALD, and a symptomatic treatment. Sensitivity analyses showed that uncertainty surrounding treatment efficacy estimates affected the model outcomes.

Postmarketing study for assessment of tolerability of a grass allergen immunotherapy tablet (GRAZAX) in patients with rhinitis or rhinoconjunctivitis.

BACKGROUND AND OBJECTIVE: Many patients with grass pollen allergy in Spain have concomitant sensitization to other allergens such as profilin. Since this type of sensitization is more common in Mediterranean countries than in countries where most patients were enrolled in clinical trials on GRAZAX (Phleum pratense 75,000 SQ-T/2, 800 BAU, ALK), the aim of this study was to analyze tolerability to GRAZAX under clinical practice conditions in patients with grass pollen allergy. METHODS: A total of 155 patients were enrolled consecutively in a prospective, open-label, observational study. Adverse reactions were recorded during the first month of treatment at 3 different timepoints: after the first dose, when patients were kept under observation for 30 minutes, and on days 15 and 30 after starting treatment RESULTS: With the first dose, 117 adverse reactions were recorded in 63 patients (40.7%). The commonest reactions (>10% patients) were oral pruritus (25.2%) and throat irritation (24.5%). Ear pruritus was recorded in 7.7%. All reactions but 1 occurred within 30 minutes of administration and all were mild-to-moderate. At the end of treatment, the percentage of patients with adverse reactions had decreased significantly (21.3%). Most adverse reactions (95.2%) were mild-to-moderate and only 3 (1.4%) were severe. No serious adverse reactions were recorded. CONCLUSION: GRAZAX seems to be well tolerated, and most reactions were mild-to-moderate. Many of these reactions occur with the first dose. Therefore, according to the Summary of Product Characteristics, the first dose has to be administered under medical supervision.

Implementation of pre-seasonal sublingual immunotherapy with a five-grass pollen tablet during optimal dosage assessment.

BACKGROUND: The optimal dose (300IR) of a five-grass pollen sublingual immunotherapy tablet in terms of efficacy was previously demonstrated from the first pollen season. OBJECTIVE: Here, we aim to confirm whether this dose remained optimal during the peak of the pollen season by assessing the efficacy and quality of life data. METHODS: A total of 628 subjects with grass pollen rhinoconjunctivitis were randomized in a double-blind, placebo-controlled, multi-centre, pan-European trial. Subjects received once-daily tablets (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before and throughout the 2005 grass pollen season. The pollen season was defined as the first day of 3 consecutive days with a grass pollen count above 30 grains/m(3) of air, recorded using Hirst-type volumetric pollen traps, to the last day before 3 consecutive days with a pollen count below 30 grains/m(3). RESULTS: The grass pollen season lasted an average of 30 days, with a peak of 12 days. The mean treatment duration before the grass pollen season was similar in the four treatment groups (121.4+/-31.1 to 128.6+/-15.4 days in the safety population). Both the 300IR and 500IR groups had highly significant improvements in Rhinoconjunctivitis Total Symptom Score (RTSS) vs. placebo at the peak pollen season (P=0.0005 and 0.0014, respectively), which agreed with improvements in RTSS in the primary evaluations. The average RTSS scores were slightly elevated during the peak pollen season in all treatment groups. The overall Rhinoconjunctivitis Quality of Life Questionnaire score confirmed the optimal dosage 300IR at peak (P<0.0001) and at the end (P< or =0.0031) of the pollen season. All doses were well tolerated. CONCLUSION: At the peak pollen season, the efficacy and quality of life data for both 300IR and 500IR groups was significantly improved vs. the placebo group. These results confirm the conclusions of the primary evaluations and validate the use of 300IR tablets for clinical practice.

Cost-effectiveness of specific immunotherapy with Grazax in allergic rhinitis co-existing with asthma.

BACKGROUND: In the United Kingdom, approximately 10.8 million people suffer from asthma, placing an economic burden on the society of more than 2 billion pounds sterling per year. For allergic asthma, treatment options consist of allergen avoidance, symptomatic treatment and allergen-specific immunotherapy (SIT). Only SIT addresses the underlying cause of the disease, reducing symptoms and offering the potential for long-term improvement. Grazax--the first tablet-based SIT--is indicated for the treatment of patients with grass pollen-induced rhinoconjunctivitis, including those with co-existing asthma. OBJECTIVE: To assess the cost-effectiveness of Grazax in patients with rhinoconjunctivitis and co-existing asthma. METHODS: A prospective pharmacoeconomic analysis was carried out as part of a multinational clinical trial assessing the efficacy of Grazax (n = 79) compared with placebo (n = 72). Both groups had access to symptomatic medication; thus the placebo group represented current standard care. Pooled data on health resource use, productivity loss because of absence from work and quality of life (Quality Adjusted Life Years, QALYs) were collected in the trial. Reduced productivity at work was estimated from the literature. A societal perspective was adopted with a 9-year time horizon. The NHS price of Grazax of 2.25 pounds sterling per tablet was used. RESULTS: The QALY gain was significantly higher for patients treated with Grazax than the placebo group receiving symptomatic medication alone (0.197 discounted QALYs gained 9 years into the future - equal to an extra 72 days of perfect health over 9 years). The levels of resource use and productivity loss were higher for the placebo group. As a result, the cost per QALY gained with Grazax was 4319 pounds sterling , which is highly cost-effective. Price sensitivity analyses demonstrated that Grazax remained cost-effective up to a tablet price of 5.07 pounds sterling . CONCLUSION: SIT with Grazax is a cost-effective strategy compared with standard management of patients with rhinoconjunctivitis and co-existing asthma.

[Economic evaluation of a tablet-based vaccination against hay fever in Denmark]. / Økonomisk evaluering af tabletbaseret vaccine mod høfeber i Danmark.

INTRODUCTION: Hay fever (allergic rhinoconjunctivitis) is a frequent disease and 12% of the Danish adult population suffer from grass-pollen induced hay fever. Symptomatic medication is the traditional treatment, while immunotherapy with sustained effect is an alternative. Grazax (Phleum pratense, ALK-Abelló) is a new tablet-based vaccination against grass-pollen induced hay fever. The aim was to investigate the cost-effectiveness of the tablet-based vaccination of grass-pollen induced hay fever in Denmark. MATERIALS AND METHODS: Based on a prospective collection of data as part of a clinical trial cost and quality of life (QALY) data for 493 patients, the tablet-based vaccine (Grazax) was compared in a cost-utility analysis (societal perspective) with symptomatic treatment. The analysis was based on three years of immunotherapy followed by six years of sustained effect. RESULTS: Significant more QALYs were gained from using the tablet-based vaccine (0.9799) compared with traditional symptomatic treatment (0.9567), which with a nine-year time horizon corresponds to 0.19 extra QALYs. The costs of vaccination against hay fever were DKK 34,498. With a nine-year time horizon, the cost per extra QALY from using the tablet-based vaccine was DKK 52,646 or DKK 134,105, focussing on direct costs alone. These results are below the unofficial thresholds for what the costs of a QALY should be. CONCLUSION: The analysis has shown that tablet-based immunotherapy (Grazax) for the treatment of hay fever results in an improved quality of life and that it is a cost-effective choice.

Comparison of costs of sublingual immunotherapy and drug treatment in grass-pollen induced allergy: results from the SIMAP database study.

OBJECTIVES: This analysis is focused on the comparison of costs of allergic rhinitis (R) alone or with allergic asthma (R + A) in grass pollen allergy, for subjects treated with sublingual immunotherapy (SLIT) and symptomatic drugs, versus standard care controls. METHODS: The SIMAP (Sublingual IMmunotherapy in Allergic Patients) study is a longitudinal observational database operated by a network of Allergy centers. Patients suffering from grass pollen allergy were included in this analysis and assigned to SLIT (plus drugs as needed) or to treatment with drugs alone. Outcome measures included use of medications, SLIT, visits and tests. Costs were assessed from the perspective of the Italian National Health Service; unit costs were obtained from published sources to produce an average cost/patient for the first year after enrolment. RESULTS: One hundred and two patients were analyzed. Demographics were comparable in the two groups. Overall per patient yearly cost of treatment was higher in SLIT patients, both in the whole sample (euro311 vs. euro180/patient), in the R (euro288 vs. euro116) and R + A (euro362 vs. euro230) subpopulations, with R + A patients generating more costs than R patients in both groups. Nevertheless considerable savings were obtained in the cost of symptomatic drugs (-22% for R; -34% for R + A) in SLIT patients. CONCLUSIONS: Other studies have shown that SLIT can reduce the use of drugs for asthma and rhinitis, but this is the first time this outcome has been demonstrated in a routine care population (in the medical practice environment of an observational study) within the first year of treatment.

Grazax: an oral vaccine for the treatment of grass pollen allergy (hay fever).

Grazax is a self-administered, once-daily, tablet-based vaccine that offers an alternative to allergy shots for adults with grass pollen allergy (hay fever). (2) Evidence from three randomized controlled trials indicates modest improvements in hay fever symptoms, with reduced use of medication to control symptoms (rescue medication use) in adults who took Grazax compared with placebo. No studies have compared Grazax with injection-based allergen immunotherapy. (3) It is not yet known if patients treated with Grazax will have a sustained tolerance to grass pollen following treatment discontinuation. (4) Adverse effects of Grazax are generally mild to moderate local allergic reactions of short duration, and include itching and swelling of the mouth, and throat irritation. (5) If Grazax becomes widely prescribed and is covered by provincial drug plans, the costs to the Canadian health care system and the impact on allergy specialist services could be substantial.

A cost-effectiveness analysis of immunotherapy with SQ allergen extract for patients with seasonal allergic rhinoconjunctivitis in selected European countries.

BACKGROUND: Seasonal allergic rhinoconjunctivitis can, for some people, reduce quality of life and the ability to cope with everyday tasks. SCOPE: In this paper we investigate the cost-effectiveness of immunization therapy with Alutard SQ (ASQ) and compare the cost-effectiveness in countries where the therapy has been in use in order to assess the impact of national therapeutic practices on the results of health economic assessments. Data are obtained from a clinical trial carried out in 2001-2002. To evaluate the cost-effectiveness of immunization we have added data on resource use in Austria, Denmark, Finland, Germany, The Netherlands, and Sweden. FINDINGS: The computations result in cost-effectiveness ratios for allergen immunization between 10,000 euros and 20,000 euros per QALY even without provision for indirect costs, and achieving dominance in most countries where indirect costs have also been taken into account. The country comparisons show that the direct cost of administrating the up-dosing and maintenance differs considerably between countries, and that the cost of medical staff is substantial, constituting in most cases more than half of the direct costs of the immunization therapy. CONCLUSION: The study shows that immunotherapy with SQ allergen extract is cost-effective in a wide range of national environments, and that cost-effectiveness differences by country are largely a result of different practices in the up-dosing phase.

Evaluation of visual analog scales for the assessment of symptom severity in allergic rhinoconjunctivitis.

BACKGROUND: The severity of rhinoconjunctivitis is typically monitored by means of nasal provocation tests (NPTs), where the nasally applied allergens trigger symptoms that are recorded using a scoring system. However, NPTs are time-consuming and stressful for patients; therefore, recording of symptoms during natural allergen exposure on visual analog scales (VASs) is increasingly being used in clinical trials. OBJECTIVES: To evaluate (1) the correlation between VAS symptom recording by patients during natural allergen exposure and symptom scoring by the physician during the NPT and (2) the possibility of replacing the more laborious and distressing allergen provocation tests with the more patient-friendly VAS. METHODS: A total of 119 patients with allergic rhinitis due to grass pollen were enrolled in the study between June 20, 2001, and January 31, 2002. Patients reported the severity of different seasonal symptoms on a VAS and underwent a NPT. RESULTS: No significant correlations between VAS and NPT scores were found. However, all the correlation coefficients between the symptom scores from the NPT and the corresponding symptom scores from the VAS were much higher for the female than the male subgroup. CONCLUSIONS: The VAS does not correlate with the NPT and, therefore, cannot replace the NPT. However, the result may suggest it worthwhile to explore the role of sex in the perception of allergy symptoms.