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.

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.

Management of Allergic Rhinitis in the United Arab Emirates: Expert Consensus Recommendations on Allergen Immunotherapy.

Allergic rhinitis (AR) is a chronic inflammatory condition of the upper airways caused by a type I hypersensitivity reaction triggered by environmental allergens. AR is associated with significant morbidity and affects patients' quality of life, emotional well-being, productivity, and cognitive functioning. As AR prevalence and morbidity have increased significantly worldwide, similar observations have been noted in the United Arab Emirates (UAE) with AR becoming a potential public health issue. Management of AR in the UAE is mainly provided by non-allergy specialists relying on first-line treatments such as intranasal steroids and antihistamines, with often suboptimal and short-term efficacy. Allergen Immunotherapy (AIT) is the only currently available disease-modifying treatment option in the form of either subcutaneous or sublingual allergen immunotherapy that has been proven to have long-term benefits. This article aims to provide recommendations regarding the use of AIT for managing AR in the UAE, considering both the current landscape in the Emirati healthcare system and local experience.

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.

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.

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.

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.

Different swelling mechanisms in nasal septum (Kiesselbach area) and inferior turbinate responses to histamine: an optical rhinometric study.

OBJECTIVE: To determine whether the inferior turbinate, which contains swelling bodies, and the nasal septum (Kiesselbach area), characterized by a dense arterial mesh, exhibit different swelling mechanisms in allergic nasal reactions. DESIGN: Two optical rhinometers were used to examine 11 patients in the clinic. Optical rhinometry is based on the transillumination of the nasal septum and inferior turbinate or the whole nose with monochromatic light. The instrument's wavelength can be adjusted to the absorption characteristics of reduced hemoglobin, oxygen-saturated hemoglobin, and water. SETTING: Outpatient university otolaryngology clinic. PATIENTS: Eleven young, healthy, nonsmoking, nonpregnant subjects (6 men and 5 women), mean age, 32.4 years (age range, 27-37 years), with no history of exposure to toxic substances, allergies, or other significant diseases. INTERVENTIONS: Optic rhinometry evaluation during the course of nasal histamine administration. MAIN OUTCOME MEASURES: Light extinction at various wavelengths. RESULTS: Following administration of histamine, in the nasal septum, the wavelength of 950 nm (edema) showed the strongest increase of light extinction; in the inferior turbinate, it was the wavelength of 786 nm (oxygenated hemoglobin). In the whole nose, the wavelength of 880 nm (edema plus hemoglobin) exhibited the largest increase of extinction. CONCLUSIONS: Swelling of the nasal septum (Kiesselbach area) in nasal allergic reactions is caused mainly by edema, whereas swelling of the inferior turbinate is due mainly to an increase in volume of blood that is highly saturated with oxygen. Swelling of the whole nose is characterized by the combination of both, edema and increase in blood volume.

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.

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.

Experimental percutaneous cannulation of the supraorbital arteries: implication for future therapy.

PURPOSE: There is some evidence to suggest that thrombolysis has a beneficial effect in retinal vessel occlusion. However, there is concern that this therapeutic approach carries the risk of hemorrhage. Retrograde cannulation of the supraorbital arteries followed by irrigation with fibrinolytic agents may have the potential to minimize the risk of major complications. The study was conducted to investigate the anatomic and sonographic features of the supraorbital arteries. METHODS: This cadaver dissection study was performed on the orbits of 12 cadaveric specimens. In each orbit, the supraorbital region was dissected, followed by cannulation of the supraorbital vessels and injection of ink. In six orbits, the orbital vessels and the distribution of the injected ink were investigated. Continuous-wave Doppler sonographic analysis of the supratrochlear and the supraorbital artery was performed in 40 orbits of 20 volunteers to measure the distance between the arteries and the midline. RESULTS: Cannulation with retrograde injection of ink was successfully performed in both the supratrochlear and the supraorbital arteries. The supratrochlear artery exhibited a more superficial course and a larger diameter than the supraorbital artery (1.08 +/- 0.19 mm vs. 0.86 +/- 0.19 mm [SD]). Dissection to the orbital apex revealed a spread of ink into the ophthalmic and the central retinal arteries. The average distance between the exit of the supratrochlear artery and the midline was found to be 16.4 +/- 1.7 mm (range, 13-20). The average distance between the exit of the supraorbital artery and the midline measured 26.5 +/- 2.6 mm (range, 23-35). CONCLUSIONS: The findings of this anatomic and sonographic study support the concept of percutaneous supraorbital vessel cannulation as a potential approach to thrombolysis in retinal vessel occlusion. The supratrochlear artery appears to provide the most reliable access route.

Extension of intracranial thrombosis after unilateral dissection of the internal jugular vein.

OBJECTIVE: Resection of the internal jugular vein can be necessary in cases of radical neck dissection or even in cases involving benign neoplasms such as glomus tumors. According to the triad described by Virchow (ie, stasis of blood flow, damage to the endothelium, and changes in hemostasis), the development of a thrombosis in the venous vessels superior to the resected internal jugular vein seems to be possible. The aim of this study was to determine the extension of possible intracranial thrombosis after wound healing. DESIGN: A total of 17 patients requiring resection of the internal jugular vein were evaluated prospectively using magnetic resonance imaging and 2-dimensional (time-of-flight) magnetic resonance angiography after the surgical treatment. Preoperative magnetic resonance images were obtained in all 17 patients for staging purposes as well as to exclude preoperative thrombosis of the internal jugular vein. Sixteen patients had malignant tumors, and 1 patient had a glomus tumor. RESULTS: Intracranial thrombosis with thrombosis of the sigmoid sinus was found in 4 patients, and thrombosis of the transverse sinus was found in 3 patients. There were no complications such as intracranial hemorrhage or signs of increased intracranial pressure in any patients. There was no evidence of intracranial thrombosis in 10 cases. In these cases, thrombosis of the venous vessels superior to the resected vein ranged from none to complete thrombosis of the superior bulb of the internal jugular vein. After unilateral resection of the internal jugular vein, the venous blood leaves the brain mainly via the venous network of the contralateral side of the neck. CONCLUSIONS: Although intracranial thrombosis of the sigmoid or transverse sinus seems to occur more frequently than was previously thought, intracranial complications such as venous infarction or increased intracranial pressure appear to be very rare. After unilateral radical neck dissection, the venous blood leaves the brain mainly via the venous system of the other side of the neck and the ipsilateral collateral veins.

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.