Treatment with the SQ tree sublingual immunotherapy tablet is safe and well tolerated in real-life.

BACKGROUND: The SQ tree sublingual immunotherapy (SLIT)-tablet is authorised for treatment of allergic rhinoconjunctivitis with or without asthma in trees of the birch homologous group in 21 European countries. The primary objective of this study was to explore the safety in real-life. METHODS: In a prospective, non-interventional post-authorisation safety study (EUPAS31470), adverse events (AEs) and adverse drug reactions (ADRs) at first administration and follow-up visits, symptoms, medication use, and pollen food syndrome were recorded by physicians in 6 European countries during the first 4-6 months of treatment. RESULTS: ADRs with the SQ tree SLIT-tablet were reported in 57.7% of 1069 total patients (median age 36.0 years, 53.7% female) during the entire observation period (severity, mild-to-moderate: 70.1%, severe: 4.7%, serious: 0.7%) and in 45.9% after first administration. ADRs were not increased with pollen exposure at first administration. With coadministration of the SQ tree and grass SLIT-tablet AEs were reported in 73.8% of patients and in 52.8% with the SQ tree SLIT-tablet alone. Nasal and eye symptoms improved in 86.9% and 80.9% of patients and use of symptomatic medication in 76.0%. PFS with symptoms was reported in 43.0% of patients at baseline and in 4.3% at the individual last visit. CONCLUSIONS: The results of this non-interventional safety study with the SQ tree SLIT-tablet confirm the safety profile from placebo-controlled clinical trials and support effectiveness in real-life according to the published efficacy data. Safety was not impaired by pollen exposure at first administration or co-administration with other SLIT-tablets.

Malaysian Society of Allergy and Immunology Consensus Statement on Sublingual Immunotherapy in Allergic Rhinitis.

Allergic rhinitis (AR) is an IgE-mediated inflammatory disease of the upper airway. AR affects the patients' quality of life, is a known risk factor for asthma and a socio-economic burden. Allergen-specific immunotherapy (AIT), comprising sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT), involves administering increasing doses of the causative allergen to induce clinical and immunologic tolerance to the allergens. It is the only currently available treatment for AR that has been proven to induce disease-modifying effects (i.e., long-term remission of allergic symptoms or potential prevention of asthma and new sensitizations). Although AIT is conventionally recommended for patients who are non-responsive to symptom-relieving pharmacotherapy, it is presently recommended as a first-line treatment for patients with moderate to severe AR who prefer a treatment with the potential for long-term remission. In light of the relatively recent implementation of AIT in Malaysia, guidelines on its appropriate indication and application are important to attain optimal outcomes. This consensus statement was developed by an expert group formed by the Malaysian Society of Allergy and Immunology to provide evidence-based recommendations for the practice of AIT in Malaysia. Patient and product selection, choice of AIT, and strategy towards an effective treatment outcome in AIT are presented.

Development and Validation Features of the Patient Benefit Index for the Treatment of Allergic Rhinoconjunctivitis with Allergen Immunotherapy.

Purpose: Allergic rhinoconjunctivitis (ARC) is one of the most common diseases worldwide. Allergen immunotherapy (AIT) is the only causal treatment available so far. Due to health policy provisions, the assessment of treatment benefit from the patient's perspective is of high relevance. To date, no instrument for assessing treatment needs and benefits of patients with ARC who receive AIT has been published. The aim of the study was to validate an instrument to assess the patient-relevant treatment benefit of patients with ARC who receive AIT. Methods: We developed the Patient Benefit Index questionnaire for AIT (PBI-AIT), consisting of 33 items. Longitudinal data of patients with ARC were used to test feasibility, reliability and validity. The PBI was compared between the beginning of the study (t1) and the end of the study (t5). Results: N = 279 patients with AIT completed the PBI-AIT at t1, n = 333 at t5; n = 226 at both timepoints. Mean number of missing values per patient was 0.7 in the Patient Needs Questionnaire (PNQ) at t1 and 1.2 in the Patient Benefit Questionnaire (PBQ) at t5. The internal consistencies measured by Cronbach's alpha were 0.98 (PNQ) and 0.99 (PBQ). The mean PBI of the patients with AIT was significantly lower at t1 and improved at t5. The PBI-AIT correlated with all tested external criteria at t5. The correlation between PBI-AIT and satisfaction with previous treatment (r = -0.57, p < 0.001) was higher than the correlation between PBI-AIT and current disease severity (r = -0.26, p < 0.001). Conclusion: The results indicate feasibility, reliability, convergent and discriminant validity as well as sensitivity to change of the PBI-AIT.

The moderating role of allergy immunotherapy in asthma progression: Results of a population-based cohort study.

BACKGROUND: Allergic asthma causes substantial morbidity and constitutes a public health burden, which increases with asthma severity. There is evidence that allergy immunotherapy (AIT) prevents the progression of allergic rhinitis (AR) to asthma. However, evidence is missing on the potential of AIT to prevent progression from milder to more severe asthma. METHODS: This population-based cohort study utilized healthcare data (2005 to 2014) from a statutory health insurance in Germany. The severity of asthma was classified according to the treatment steps recommended by the global initiative for asthma (GINA). The effect of AIT on the transition between the GINA steps was analyzed using multivariable Cox regression models adjusted for age and sex. RESULTS: From the total cohort of 1,739,440 patients, 39,167 individuals aged 14 years or older were classified as having incident asthma during the observation period and were included in the study. From these, 4111 patients (10.5%) received AIT. AIT exposure was associated with a significantly decreased likelihood of asthma progression from GINA step 1 to GINA step 3 (HR 0.87; 95% CI 0.80-0.95) and GINA step 3 to GINA step 4 (HR 0.66; 95% CI 0.60-0.74). GINA medication for step 2 and step 5 was rarely prescribed. CONCLUSIONS: This observational study in a real-world setting indicates that patients with allergic asthma who receive AIT are less likely to experience progression of asthma severity than asthma patients not receiving AIT.

Is allergy immunotherapy with birch sufficient to treat patients allergic to pollen of tree species of the birch homologous group?

Pollen from various Fagales tree species prolongs the season and makes tree pollen allergy a major health problem. Despite involving the same causative allergens, allergy immunotherapy (AIT) treatment habits differ significantly across different geographical regions. Diagnosis and treatment with AIT in patients allergic to tree pollen were discussed by a group of German medical experts who give practical recommendations based on the available data. Regulatory perspective: According to current guidelines on allergen products, birch pollen are the representative allergen source of the birch homologous group including several Fagales trees based on sequence and structural similarity of their allergen proteins. Immunological perspective: A high level of IgE cross-reactivity towards allergens from the birch homologous group has been observed in basic research and clinical trials. Clinical perspective: Clinical trial data show that the efficacy of birch pollen AIT is not only related to birch pollen allergy but extends to pollen from other trees, especially alder, hazel and oak. In order to optimize diagnosis and treatment of tree pollen allergy, the experts recommend to focus diagnosis and respective treatment with AIT primarily to birch as the representative allergen of the Fagales tree homologous group, but further diagnostics may be needed for some patients to determine adequate treatment.

Intra-Seasonal Initiation of the SQ-Standardised Grass Allergy Immunotherapy Tablet Routinely Applied by Allergy Specialists and General Practitioners with Experience in Treatment of Allergy: A Non-Interventional Observational Study.

INTRODUCTION: Intra-seasonal start of treatment with the SQ® grass sublingual immunotherapy (SLIT) tablet (GRAZAX®, ALK, Denmark) has been previously demonstrated to be well-tolerated. The objective of our study was to investigate the tolerability of intra-seasonal start of treatment comparing patients treated by allergists and general practitioners experienced in treatment of allergy (GPs). METHODS: In a non-interventional, open-label, observational study, data on intra-seasonal start with the SQ® grass SLIT tablet were recorded in patients treated by allergists and GPs in Germany. Adverse events (AEs) were recorded by the physicians at first administration and during the 1-3-month observation period. The tablets taken and any AEs were recorded by the patients in diaries for the first 14 days. RESULTS: Treatment with the SQ® grass SLIT tablet was started in 198 patients, and in 179 intra-seasonal (allergists: 140, GPs: 39) and 19 post-seasonal; average treatment period was 47 days. AEs related to intra-seasonal start were reported in 43.6% of patients; no relevant differences between allergists and GPs were observed. In the subgroup of GPs, patients were younger (p = 0.0191), had more frequently asthma (p = 0.0043), more patients used symptomatic medication in the previous pollen season (p = 0.0198) and were more frequently treated for other diseases (p = 0.0467). In the allergists subgroup, more diagnostic allergy tests were applied (p < 0.0001) with less anti-allergic premedication at first administration (p = 0.0026). CONCLUSION: The intra-seasonal start of treatment with the SQ® grass SLIT tablet in patients routinely treated by allergists or GPs with experience in treatment of allergy was well-tolerated, although patient characteristics were different with respect to age, frequency of asthma and concomitant allergies, use of symptomatic medication in the previous grass pollen season and concomitant treatment of other diseases. The safety profile from a previous placebo-controlled clinical trial and data from a previous real-life study on intra-seasonal start performed by allergists were confirmed.

Tolerability of an Immunologically Enhanced Subcutaneous Immunotherapy Preparation in Patients Treated with Concomitant Allergy Immunotherapy: A Non-Interventional Observational Study.

BACKGROUND: For causal treatment by allergy immunotherapy (AIT) a single or few allergen products for the clinically most relevant allergens are applied to treat multiple allergies, but few data on the tolerability of multiple AIT applications are available. OBJECTIVE: The aim of our study was to investigate safety and tolerability in patients treated by subcutaneous immunotherapy (SCIT) and concomitant SCIT or sublingual immunotherapy (SLIT) products. METHODS: In a non-interventional, observational study in Germany treatment of patients with a primary SCIT and concomitant AIT (SCIT or SLIT) was documented during the first 4 months of treatment. Adverse events (AEs) were recorded by the physicians and by patients in diaries, and coded using the Medical Dictionary for Regulatory Activities (MedDRA). RESULTS: Three hundred and seven patients were treated with the primary SCIT by 79 allergists, and 271 received a concomitant AIT. AEs were reported in 92 (33.9%) patients and adverse drug reactions (ADRs) in 63 (23.2%) patients related to the primary SCIT and in 69 (25.5%) to the concomitant AIT; six (2.2%) patients discontinued due to ADRs. ADRs were mild or moderate in 40 (14.8%) patients, severe in 23 (8.5%), and serious in one patient. The most frequent reactions were local swelling and pruritus. Overall tolerability was assessed as 'good' or 'very good' by 95.6% of patients and 96.7% of physicians. CONCLUSIONS: Compared with data from a large previous study no increase in the frequency of ADRs in real life or change in the tolerability profile was observed for SCIT with concomitant SCIT or SLIT.

Patient preferences in allergy immunotherapy (AIT) in Germany - a discrete-choice-experiment.

BACKGROUND: Allergic Rhinitis (AR) is a common disorder in Europe with Allergic Asthma (AA) as a frequent comorbidity. Allergy immunotherapy (AIT) is the only causal therapy of AR and AA, and can be administered as subcutaneous injections at the physician or as sublingual drops or tablets at home. The usual treatment duration is 3 years. OBJECTIVE: This study aimed to elicit patient preferences to identify the AIT administration mode preferred by patients. METHODS: A discrete-choice-experiment (DCE) was developed to determine how people weight different treatment options using a paper-based questionnaire from June to September 2014, including 16 study centres. Main inclusion criteria: >18 years, grass, birch and/or house dust mite AR with moderate to severe symptoms, AIT-naïve and AIT-indicated. DCE-attributes were: Administration form, number and duration of physician visits, frequency of life-threatening anaphylactic shocks, local side-effects and co-payments. RESULTS: Two-hundred thirty-nine subjects participated, resulting in analysable 1842 choices. All attributes were significant predictors for the treatment-choice. Ranked by importance, the following first three attributes are most preferred by patients: 1(st) Number and duration of physician visits: Fewer visits with shorter duration preferred (0.658*) 2(nd) Frequency of life-threatening anaphylactic shocks: Lower risk of shocks preferred (0.285*) 3(rd) Local side-effects: Preference for rash/swelling on upper arm over itching/swelling under the tongue (0.210*) (*coefficient-size represents relative importance of the attributes) CONCLUSION: The most important attribute is the number and duration of visits to a physician. A lower risk of life-threatening anaphylactic shocks was ranked as the second whereas co-payments and administration form play a limited role.

Health-Related Quality of Life During Routine Treatment with the SQ-Standardised Grass Allergy Immunotherapy Tablet: A Non-Interventional Observational Study.

BACKGROUND AND OBJECTIVE: Allergy immunotherapy (AIT) with the SQ(®) grass sublingual immunotherapy (SLIT)-tablet has been shown to be efficacious, well-tolerated and to improve disease-specific health-related quality of life (HRQoL) in controlled clinical trials. The aim of our study was to investigate HRQoL in patients with allergic rhinoconjunctivitis routinely treated with the SLIT-tablet and taking symptomatic medication as needed compared with patients treated only with symptomatic medication. METHODS: In a non-interventional, open-label study, patients treated with the SLIT-tablet were observed for about 12 months compared with patients only symptomatically treated. Patients assessed their HRQoL with the 12-Item Short Form Health Survey (SF-12) and the Rhinitis Quality of Life Questionnaire (RQLQ) in the grass pollen seasons (GPS) at baseline (GPS1, HRQoL1), after GPS1 (HRQoL2) and in the following GPS (GPS2, HRQoL3). Tolerability, compliance, symptoms and medication use were assessed in the SLIT-tablet group by the physician. RESULTS: Overall, data were analysed in 576 patients. Mean differences (±SD) in overall scores for HRQoL3 versus HRQoL1 (186 patients) of SF-12 were +11.4 ± 16.8 (SLIT-tablet) and -3.4 ± 15.7 (symptomatic medication), (p < 0.0001), and of RQLQ -1.31 ± 1.07 and +0.10 ± 0.74 (p < 0.001), and for HRQoL3 versus HRQoL2 (238 patients) of SF-12 -1.6 ± 15.3 and -10.0 ± 14.1 (p = 0.0003), and of RQLQ +0.22 ± 1.29 and +1.24 ± 1.30 (p < 0.0001). Tolerability and adherence for the SLIT-tablet were comparable with data of other non-interventional studies. CONCLUSIONS: Routine treatment with the SQ(®) grass SLIT-tablet resulted in clear improvements in disease-specific and general quality of life, while no improvements were observed in patients treated only symptomatically.

Allergy immunotherapy for allergic rhinitis effectively prevents asthma: Results from a large retrospective cohort study.

BACKGROUND: Allergic rhinitis (AR) is a main risk factor for the development of asthma. Two randomized open-label trials indicated that allergy immunotherapy (AIT) prevents the onset of asthma in patients with AR. However, these trials have methodological limitations, and it is unclear to what extent this experimental efficacy translates into clinical effectiveness. OBJECTIVES: We sought to investigate the effectiveness of AIT to prevent asthma in patients with AR. METHODS: Using routine health care data from German National Health Insurance beneficiaries, we identified a consecutive cohort of 118,754 patients with AR but without asthma who had not received AIT in 2005. These patients were stratified into one group starting AIT in 2006 and one group receiving no AIT in 2006. Both groups were observed regarding the risk of incident asthma in 2007 to 2012. Risk ratios (RRs) were calculated with generalized linear models by using a Poisson link function with robust error variance and adjustment for age, sex, health care use because of AR, and use of antihistamines. RESULTS: In a total of 2431 (2.0%) patients, AIT was started in 2006. Asthma was newly diagnosed from 2007-2012 in 1646 (1.4%) patients. The risk of incident asthma was significantly lower in patients exposed to AIT (RR, 0.60; 95% CI, 0.42-0.84) compared with patients receiving no AIT in 2006. Sensitivity analyses suggested significant preventive effects of subcutaneous immunotherapy (RR, 0.54; 95% CI, 0.38-0.84) and AIT including native (nonallergoid) allergens (RR, 0.22; 95% CI, 0.02-0.68). AIT for 3 or more years tended to have stronger preventive effects than AIT for less than 3 years. CONCLUSION: AIT effectively prevents asthma in patients with AR in a real-world setting. Confounding by indication cannot be excluded but would lead to an underestimation of the true preventive effects of AIT.

Tolerability of the SQ-standardised grass sublingual immunotherapy tablet in patients treated with concomitant allergy immunotherapy: a non-interventional observational study.

BACKGROUND: The majority of allergic patients are poly-sensitized. For causal treatment by allergy immunotherapy (AIT) a single or few allergen products containing the clinically most relevant allergens are applied, but few data on tolerability of multiple application of AIT is available. The aim of our study was to investigate safety and tolerability in patients who started treatment by sublingual immunotherapy (SLIT) with the standardised SQ(®) grass SLIT-tablet and were treated with concomitant AIT products. METHODS: In a non-interventional, open-label, observational study in Germany treatment of patients with the SQ(®) grass SLIT-tablet and concomitant AIT (SCIT or SLIT) was documented between January 2012 and January 2014. Patients were followed at visits at first administration of the SQ(®) grass SLIT-tablet and after 1-3 months of treatment. Tolerability of the treatment with the SQ(®) grass SLIT-tablet and concomitant AIT were assessed by the physician and administration of AIT and adverse events (AEs) were recorded by the patients in diaries. AEs and adverse drug reactions (ADRs) were coded by using the Medical Dictionary for Regulatory Activities. RESULTS: In total, 181 patients were documented by 48 allergists and 160 patients treated with a concomitant AIT (SCIT 130, SLIT 30). AEs were reported in 58 (36.3 %) patients with concomitant AIT, and AEs considered related with the SQ(®) grass SLIT-tablet in 49 (30.6 %) and with concomitant AIT in 18 (11.3 %) patients. Treatment was discontinued due to ADRs in 12 (7.5 %) patients and severity of ADRs was assessed mild or moderate in 29 (18.1 %), and severe in 20 (12.5 %) patients. Most common reactions were localised at the application site of the SQ(®) grass SLIT-tablet as oral pruritus, throat irritation, oedema mouth and paraesthesia oral; no serious ADRs were reported. Overall tolerability of the SQ(®) grass SLIT-tablet if given with concomitant AIT was assessed as "good" or "very good" by 91.0 % of patients and 91.6 % of physicians. CONCLUSIONS: In comparison to data from previous studies no increase in frequency of AEs or change in the tolerability profile was observed when SLIT with the SQ(®) grass SLIT-tablet was administered with concomitant SCIT or SLIT.

Safety and tolerability of an intra-seasonal initiation of the SQ-standardised grass allergy immunotherapy tablet: a non-interventional observational study investigating the feasibility during routine administration.

BACKGROUND AND OBJECTIVE: For specific immunotherapy to pollen allergy, a pre-seasonal start of treatment is recommended by international guidelines. In a placebo-controlled clinical trial with adults, an intra-seasonal start of therapy with the SQ-standardised grass allergy immunotherapy tablet (AIT) was well-tolerated. The objective of our study was to investigate the feasibility of an intra-seasonal start of grass AIT administered during routine treatment by practising allergists. METHODS: In a multicentre, prospective, open-label, uncontrolled, non-interventional observational study, data on routine treatment with grass AIT were recorded in patients who started administration of tablets within the 2010 grass pollen season in Germany. Adverse events (AEs) were recorded by the physician at visits for the first administration in the clinic and at the end of the 1- to 3-month observation period. AEs and daily administration of the tablet were recorded by the patients in diaries for the first 14 days. Treatment satisfaction, global tolerability and perceived effect of treatment were assessed by the patient and physician at the end of the study. RESULTS: A total of 662 patients were treated with 1 tablet daily by 286 physicians. Grass AIT was started intra-seasonally in 620 patients and post-season in 42. The average treatment period was 51.6 days. AEs were recorded in 52.1 % of all patients and in 35.6 % at first administration, with throat irritation (21.3 %), paraesthesia oral (19.9 %), oral pruritus (14.0 %) and ear pruritus (10.3 %) being the most frequent AEs related to grass AIT. The intensity of the AEs was assessed as mild or moderate in 42.1 % of patients and severe in 8.0 %; AEs related to grass AIT were classified as serious in two patients. Grass AIT was discontinued due to AEs in 7.7 % of patients. Diaries were evaluable for 77.0 % of patients; the average rate of patients with AEs decreased continuously from 44.7 % (day 1) to 26.9 % (day 14) and the average daily rate of patients who forgot to take their tablet was about 5 %. Overall tolerability was assessed by 87.2 % of patients and 91.4 % physicians as "very good" or "good" and effectiveness of treatment was assessed as "very good" or "good" in 81.4 % of patients and 85.8 % of physicians. More than 90 % of patients and physicians were satisfied with the treatment. CONCLUSION: The tolerability data for an intra-seasonal start of grass AIT during routine treatment confirm the safety profile from the previous controlled trial. Tolerability was assessed as good in combination with high satisfaction with the treatment and compliance.

Immunologic effect and tolerability of intra-seasonal subcutaneous immunotherapy with an 8-day up-dosing schedule to 10,000 standardized quality-units: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: International guidelines recommend that allergen-specific immunotherapy for pollen-induced rhinoconjunctivitis is initiated preseasonally. However, because subjects often present to physicians with allergy symptoms during the pollen season, "within-season" initiation of specific immunotherapy is of special interest. OBJECTIVE: We evaluated the immunomodulatory effects and tolerability of subcutaneous immunotherapy (SCIT) with Standardized Quality (SQ) 6-grass mix and rye allergen extract, using an 8-day intra-seasonal up-dosing schedule to 10,000 SQ-units (SQ-U). METHODS: In a 9-week, multicenter, randomized, double-blind, placebo-controlled trial, adults (mean age, 34.6 years; 99.3% whites) with grass pollen-induced rhinoconjunctivitis (mean disease duration, 15.1 years) were randomized 3:1 to receive SCIT or placebo. Treatment was initiated during the 2008 pollen season, with an 8-day up-dosing from 100 to 10,000 SQ-U (6 daily injections) followed by 2 maintenance injections of 10,000 SQ-U at intervals of 2 and 4 weeks, respectively. The primary end point examined immunologic effects, assessing the difference in IgE-blocking factor (serum components competing with IgE for allergen binding) between SCIT and placebo at week 9. Secondary/explorative end points included the difference in IgE-blocking factor, specific IgG(4), and specific IgE at various times. Tolerability (adverse events, local and systemic allergic reactions) of the up-dosing schedule was also evaluated. RESULTS: Of the 148 treated subjects 144 (SCIT n = 109; placebo n = 35) were analyzed for the primary parameter. Immunologic response (significantly higher increase in IgE-blocking factor and IgG(4) levels) occurred with SCIT versus placebo at week 9 (IgE-blocking factor, P = 0.0017; IgG(4,)P = 0.0215). Significant differences were observed as early as week 3. AEs were reported in 60.7% of SCIT- and 30.6% of placebo-treated subjects, with no treatment-related serious AEs. Local allergic reactions occurred in 46.4% of SCIT and 8.3% of placebo subjects (χ(2) test, P < 0.0001). No significant difference was observed between groups in the incidence of systemic reactions (7.1% SCIT vs 5.6% placebo; χ(2) test, P = 0.7413). CONCLUSIONS: This trial provides the first description of short (8-day) intra-seasonal up-dosing with SCIT, which induced immunologic effects after only 3 weeks, and was generally well tolerated, although it induced a marked increase in the rate of local reactions compared with placebo. ClinicalTrials.gov identifier NCT00807547; ALK trial ID SHX0562.

Immunologic effects and tolerability profile of in-season initiation of a standardized-quality grass allergy immunotherapy tablet: a phase III, multicenter, randomized, double-blind, placebo-controlled trial in adults with grass pollen-induced rhinoconjunctivitis.

BACKGROUND: The summary of product characteristics of the grass allergy immunotherapy tablet (AIT) (Phleum pratense grass pollen allergen extract) states that clinical effect may be observed in the first pollen season of treatment, if treatment is initiated ≥2 months (8 weeks) before the start of the grass pollen season. However, because patients with grass allergy may first present to physicians during the season, immediate treatment initiation (ie, in-season initiation) may increase treatment compliance and reduce the risk for disease progression compared with asking patients to return before the next pollen season to initiate treatment. This "in-season approach" may offer more patients the potentially beneficial treatment option of specific immunotherapy. However, to date, the immunomodulatory effects and tolerability of in-season treatment initiation is unknown. OBJECTIVE: The aim of this study was to assess the immunologic effects and tolerability of in-season initiation of treatment with the grass AIT. METHODS: This multicenter, randomized, double-blind, placebo-controlled trial was carried out in Germany and Austria. Adults with grass pollen allergy (positive skin-prick test and specific grass-pollen immunoglobulin [Ig] E) and grass pollen-induced moderate to severe persistent rhinoconjunctivitis were enrolled. Patients were randomly assigned to receive once-daily grass AIT or placebo, starting during the 2008 grass pollen season and continuing for 8 to 10 weeks. The primary end point was change from baseline in IgE-blocking factor (serum components competing with IgE for allergen binding). Secondary end points included changes from baseline in specific IgE and IgG(4) and measures of tolerability (assessed mainly by adverse events [AEs]). Blood samples for immunologic assessment were obtained by the investigators at baseline and after treatment. All AEs observed by the investigator and/or reported by the patient were recorded throughout the trial and follow-up. RESULTS: A total of 276 patients were enrolled and formed the full analysis set (mean age, 35 years; 55% men, 45% women; 99% white; mean weight, 76 kg; history of asthma, 41%; mean duration of grass allergy, 15.1 years). No major differences in medical history were found between the grass AIT group (n = 219) and the placebo group (n = 57). The change from baseline in mean concentration of IgE-blocking factor was significantly greater with grass AIT compared with placebo (+0.14 vs +0.05; P < 0.0001). The changes from baseline in specific IgE and specific IgG(4) concentrations were significantly greater with AIT compared with placebo (IgE, +0.59 vs +0.21 log kU/L; IgG(4), +0.18 vs +0.04 log relative units; both, P < 0.0001). At least 1 AE was reported in 58% of patients in the AIT group and in 40% of patients in the placebo group. Most AEs considered related to AIT were mild or moderate events in the mouth, throat, and/or ears (eg, oral pruritus). Four serious AEs were reported in the AIT group (sinusitis, road traffic accident, salmonellosis, meniscus lesion), but all were considered unlikely to be related to treatment. Three percent of the grass AIT group and 2% of the placebo group were withdrawn from the trial due to an AE. CONCLUSIONS: In-season initiation of grass AIT was associated with an immunomodulatory response in terms of induction of IgE-blocking factor, specific IgE, and specific IgG(4). In-season initiation of grass AIT was generally well tolerated in this group of adults with moderate to severe grass pollen-induced rhinoconjunctivitis. These findings are consistent with those related to the preseasonal initiation of AIT therapy.

Optical rhinometry: application on children and adolescents for nasal provocation tests.

Optical rhinometry is a new method that allows the direct, real time measurement of changes in swelling of the nasal mucosa by external measurement. The measurement is carried out with monochromatic near-infrared light. The change of intensity of the swelling is displayed and recorded. Different preceding studies on adults already showed the reliability and absence of side effects of the measuring method. With the help of a prototype of an optical rhinometer specially developed for children, 65 measurements were performed on a total of 13 children and adolescents having one-sided nasal provocation tests with histamine and allergens, negative provocation tests with control solution and decongestion with xylometazoline. The nasal provocation tests were implemented by optical rhinometry while simultaneously using the established method of active anterior rhinomanometry. We found significant differences between positive and negative provocation tests in both methods (p < 0.01). Decongestion was different from all other groups in both methods (p < 0.01). No clear connection could be made between the percentage increase of rhinometric extinction and the percentage increase of obstruction measured by anterior rhinomanometry. The evaluation of the nasal provocation test via continuous direct measurement of swelling of the nasal mucosa membrane seems feasible in children. Data which so far could not be measured, such as the beginning of swelling and the time of the maximum state of swelling, might increase the diagnostic validity of provocation tests.

Comparison of optical rhinometry and active anterior rhinomanometry using nasal provocation testing.

OBJECTIVE: To investigate whether there is a correlation between active anterior rhinomanometry (RMM) and optical rhinometry (ORM) data in the detection of changes in nasal congestion. DESIGN: In 70 subjects both ORM and RMM were performed. Changes in nasal congestion were induced by nasal provocation with histamine, allergens, solvent, and xylometazoline hydrochloride, 0.1%. Using visual analog scales, subjects rated the degree of nasal congestion and how comfortable each of the 2 measures was. In total, 136 measurements were evaluated. SUBJECTS: Seventy subjects were included in the study. All had a normal otorhinolaryngologic status with no acute or chronic infections. INTERVENTIONS: Nasal provocation tests with allergens, histamine, control solution, or xylometazoline were performed. MAIN OUTCOME MEASURES: Congestion or decongestion of the nasal mucosa was measured via nasal resistance (RMM), changes in light absorption of the nasal tissue (ORM), and visual analog scale. RESULTS: When comparing the relative change in light extinction in ORM with nasal airflow in RMM, we found correlation coefficients up to r = -0.69. Results from RMM were correlated with the subjects' ratings of nasal congestion (r = -0.63). In comparison, the correlation coefficient between these ratings and ORM was r = 0.84. In addition, ORM was rated to be more comfortable than RMM. CONCLUSIONS: The subjects' ratings of nasal congestion correlated to a higher degree with the results from ORM than with those from RMM. In addition, ORM was rated as more comfortable than RMM. Overall, ORM appeared to be a valid technique for the assessment of changes in nasal congestion.