Grass Pollen-induced Allergic Rhinoconjunctivitis Research Articles

Clinical relevance of pre- and coseasonal sublingual immunotherapy with a 300 index of reactivity 5-grass SLIT tablet in allergic rhinoconjunctivitis.

There is considerable interest in improving the scoring methods for evaluating the efficacy of allergen immunotherapy (AIT) and to show if this is associated with clinically meaningful results from the patient's perspective. We aimed to assess the efficacy and clinical relevance of a 300 index of reactivity (IR) 5-grass pollen sublingual immunotherapy (SLIT) tablet in children, adolescents and adults with moderate to severe grass-induced allergic rhinoconjunctivitis (ARC) with or without controlled asthma using the combined symptom and medication score CSMS0-36 . The data of the European population that participated in 3 Phase III, international, randomized double-blind placebo-controlled clinical trials were analyzed post hoc. A total of 864 patients randomized to 300 IR 5-grass tablet or placebo were analyzed. Over the primary evaluation period, the difference in CSMS0-36 between the 300 IR and placebo groups was statistically significant (point estimates: -2.51, CI95% [-3.88; -1.14], p<0.0001 in clinical trial1; -2.31, CI95% [-3.39; -1.23], p<0.0001 in CT2; and -2.31, CI95% [-3.58; -1.03], p=0.0004 in CT3). The relative differences between the 300 IR 5-grass tablet and placebo were -29.7%, -33.8%, and -26.3%, respectively. The results based on CSMS0-36 were consistent with those obtained with the primary endpoints of the trials and support the consideration of the 2-point threshold of the CSMS0-36 for clinical relevance of AIT. Post hoc analysis of 3 CTs with the 300 IR 5-grass SLIT tablet confirmed its significant and clinically relevant effect in the European population with grass pollen-induced ARC with or without controlled asthma.

Face masks suitable for preventing COVID-19 and pollen allergy. Astudy in the exposure chamber.

BackgroundSince the outbreak of the coronavirus pandemic, the population in Germany has been asked to wear face masks in public areas. The masks are accepted by the public. People with a pollen allergy have an interest in knowing whether masks can also provide protection against pollen and thus prevent symptoms even without medication.MethodIn order to evaluate the potential ‘antipollen effect’ of face masks, 14 adults with confirmed grass pollen-induced allergic rhinoconjunctivitis were exposed to grass pollen for a period of two hours following a standardised protocol. The test was conducted outside of the grass pollen season. The subjects wore either no mask, a medical mask or a FFP2 mask.ResultsSubjects wearing either mask were clearly able to avoid both nasal and conjunctival symptoms. There were no significant differences between the two masks in terms of effect. Mask wearing to prevent pollen exposure clearly supports overall well-being.ConclusionWearing a mask during pollen season can be recommended as an effective nondrug option for people with a pollen allergy.Supplementary InformationThe online version of this article (10.1007/s40629-021-00180-8) contains supplementary material, which is available to authorized users.

Persistence of the clinical effect of grass allergen peptide immunotherapy after the second and third grass pollen seasons

Grass allergen peptides are in development for the treatment of grass pollen-induced allergic rhinoconjunctivitis. Aprevious randomized, placebo-controlled study demonstrated that grass allergen peptides significantly improved total rhinoconjunctivitis symptom scores (TRSSs) after posttreatment challenge (PTC) to rye grass in an environmental exposure unit after 1 intervening grass pollen season (GPS1). We sought to evaluate the efficacy/safety of 4 dosing regimens of grass allergen peptides after a second (GPS2) and third (GPS3) intervening GPS in the environmental exposure unit. Eligible subjects who were randomized in the parent study (GPS1) during the first year of recruitment were invited to participate in GPS2 and GPS3, which took place 1 and 2 years after treatment cessation, respectively. Participants were not treated further, and both participants and study personnel remained blinded. The primary efficacy end point was the change in mean TRSS (reported every 30 minutes) from GPS1 baseline to the follow-up PTC calculated across all time points over days 2 to 4 for GPS2 and across hours 1 to 3 over days 2 to 4 for GPS3. Secondary efficacy end points and safety were also assessed. One hundred twenty-two and 85 participants were enrolled in GPS2 and GPS3, respectively. Anumerically greater, but not statistically significant improvement from baseline in mean TRSS at PTC was observed in the group receiving one 6-nmol intradermal injection every 2 weeks for 14 weeks group compared with the placebo at GPS2 (-6.0 vs -3.6, P= .0535) and GPS3 (-6.2 vs -3.6, P= .1128). Similar findings were observed for the group receiving one 6-nmol intradermal injection every 2 weeks for 14 weeks at GPS3 (-6.4 vs -3.6, P=.0759). No adverse safety signals were detected. Treatment with grass allergen peptides led to an improvement in allergic rhinoconjunctivitis symptoms after 3 intervening GPSs, corresponding to up to 2 years off treatment.

Reliability of a New Symptom Score in a Titrated Quantitative Conjunctival Provocation Test Supported by an Objective Photodocumentation

Background: Allergen provocation tests are useful methods for proving the clinical relevance of an allergen-specific sensitization. Among these methods, the conjunctival provocation test (CPT) represents an easy-to-use tool. However, its readout parameters have not yet been internationally standardized or validated. Photodocumentation has been shown as a good option for objectifying a CPT reaction, supporting the local investigator assessment. Based on test-retest reliability of the score and an objective digital photoanalysis of the conjunctival redness, this study aimed to prove the reproducibility of a new CPT scoring system for use in clinical trials (ClinicalTrials.gov identifier: NCT02690740). Methods: A titrated quantitative CPT was conducted outside of the pollen season in a final cohort of 23 adult patients with birch or grass pollen-induced allergic rhinoconjunctivitis. Conjunctival symptoms were analyzed using a standardized symptom score. Conjunctival redness was also evaluated by an external observer and correlated with a digital photoanalysis using MATLAB software. Results: A test-retest correlation of 0.6 (p < 0.01) was found for the symptom score results. Likewise, a correlation of 0.65 (p < 0.01) was observed in the digital photoanalysis. The total symptom score showed a decrease in the mean value of 0.48 score points in the retest. Conclusions: This study reveals both a valuable test-retest correlation of the proposed score as well as a good correlation of eye redness with the (objective) photodocumentation. Based on our results, we can recommend the use of this scoring system as a valuable clinical protocol for future clinical trials.

Safety of 300IR 5-Grass Tablet in Children with Grass Pollen-Induced Allergic Rhinoconjunctivitis: Results of an Observational, Post-Marketing Safety Study

Safety of 300IR 5-Grass Tablet in Children with Grass Pollen-Induced Allergic Rhinoconjunctivitis: Results of an Observational, Post-Marketing Safety Study

Dose-Finding Study of Carbamylated Monomeric Allergoid Tablets in Grass-Allergic Rhinoconjunctivitis Patients

To determine the optimal effective and safe dose of sublingual immunotherapy tablets containing carbamylated monomeric allergoids in patients with grass pollen-induced allergic rhinoconjunctivitis. In this prospective, randomized, double-blind, active-controlled, multicenter, Phase II study, four different daily doses were applied preseasonally for 12 weeks. Of 158 randomized adults, 155 subjects (safety population) received 300 units of allergy (UA)/day (n=36), 600 UA/day (n=43), 1000 UA/day (n=39), or 2000 UA/day (n=37). After treatment, 54.3, 47.6, 59.0 and 51.4% of patients, respectively, ceased to react to the highest allergen concentration in a conjunctival provocation test. Furthermore, the response threshold improved in 70.4, 62.9, 76.7 and 66.7% of patients, respectively. No serious adverse events occurred. This study found 1000 UA/day to be the optimal effective and safe dose.

Safety Review of 5-Grass Pollen Tablet from Pooled Data of Clinical Trials

The 5-grass pollen sublingual tablet has been approved for the treatment of grass pollen-induced allergic rhinoconjunctivitis in subjects with or without intermittent asthma. To provide a comprehensive analysis of the safety profile of the 5-grass tablet on the basis of pooled data from 8 clinical trials. Subjects (5-65 years old) with medically confirmed grass pollen-induced allergic rhinoconjunctivitis were included in the double-blind studies. Those with intermittent asthma not requiring treatment other than inhaled beta-2 agonists could participate. Randomized subjects received a 5-grass or placebo tablet daily 2 or 4 months preseasonally and coseasonally (5single-season studies, over 3 years in a long-term study) or outside the season (phase I studies). Adverse events were pooled and analyzed descriptively. Among 2,512 subjects enrolled, 1,514 received the 5-grass tablet. A total of 1,038 adults and 154 pediatric (5-17years old) subjects were treated with the 300 Index of Reactivity dose (vs 840 and 158 placebo recipients, respectively); 17% had intermittent asthma, and 62% were polysensitized. Adverse reactions (ADRs) reported in more than 10% of actively treated subjects were mild or moderate application-site reactions, for example, oral pruritus 25% (placebo 4%) and throat irritation 21% (placebo 3%). These generally occurred during the first week of treatment and decreased over time. They led to discontinuation in less than 2.5% of subjects. None of the 3serious ADRs were reports of anaphylaxis. No notable differences were detected in terms of incidence, nature, and severity of ADRs between adult and pediatric populations, nor between subjects with or without asthma. The pooled analysis in 1,514 subjects from 8 clinical studies demonstrates that the 5-grass pollen sublingual tablet has a similar good safety profile in adult and pediatric patients with or without mild, intermittent asthma.

Treatment with grass allergen peptides improves symptoms of grass pollen–induced allergic rhinoconjunctivitis

Synthetic peptide immunoregulatory epitopes are a new class of immunotherapy to treat allergic rhinoconjunctivitis (ARC). Grass allergen peptides, comprising 7 synthetic T-cell epitopes derived from Cyn d 1, Lol p 5, Dac g 5, Hol l 5, and Phl p 5, is investigated for treatment of grass pollen-induced ARC. We sought to evaluate the efficacy, safety, and tolerability of intradermally administered grass allergen peptides. A multicenter, randomized, double-blind, placebo-controlled study evaluated 3 regimens of grass allergen peptides versus placebo in patients with grass pollen-induced allergy (18-65years). After a 4-day baseline challenge to rye grass in the environmental exposure unit (EEU), subjects were randomized to receive grass allergen peptides at 6nmol at 2-week intervals for a total of 8 doses (8x6Q2W), grass allergen peptides at 12nmol at 4-week intervals for a total of 4 doses (4x12Q4W), or grass allergen peptides at 12nmol at 2-week intervals for a total of 8 doses (8x12Q2W) or placebo and treated before the grass pollen season. The primary efficacy end point was change from baseline in total rhinoconjunctivitis symptom score across days 2 to 4 of a 4-day posttreatment challenge (PTC) in the EEU after the grass pollen season. Secondary efficacy end points and safety were also assessed. Two hundred eighty-two subjects were randomized. Significantly greater improvement (reduction of total rhinoconjunctivitis symptom score from baseline to PTC) occurred across days 2 to 4 with grass allergen peptide 8x6Q2W versus placebo (-5.4 vs -3.8, respectively; P=.0346). Greater improvement at PTC also occurred for grass allergen peptide 8x6Q2W versus placebo (P=.0403) in patients with more symptomatic ARC. No safety signals were detected. Grass allergen peptide 8x6Q2W significantly improved ARC symptoms after rye grass allergen challenge in an EEU with an acceptable safety profile.

ASCIA‐P51: SAFETY OF 300IR 5‐GRASS POLLEN SUBLINGUAL TABLET FOR THE TREATMENT OF GRASS POLLEN‐INDUCED ALLERGIC RHINOCONJUNCTIVITIS IN ADULTS AND PEDIATRIC SUBJECTS WITH INTERMITTENT ASTHMA

Allergic asthma is frequently associated with grass pollen-induced allergic rhinoconjunctivitis (ARC). Here we present the safety experience across the development program for the 300IR 5-grass pollen sublingual tablet by asthma status. Subjects with medically confirmed grass pollen-induced ARC were included in one of seven double-blind studies. Those with intermittent asthma not requiring treatment other than inhaled beta-2 agonists (GINA treatment Step 1) could participate. Adverse events (AEs) pooled from the studies were analyzed descriptively. Asthma status was recorded at randomization. The analysis included 1,878 adults and 312 pediatric subjects. Of these, 328 (17%) adults (300IR = 179, Placebo = 149) and 66 (21%) pediatrics (300IR = 32, Placebo = 34) had intermittent asthma at baseline. Percentages of actively-treated subjects reporting drug-related AEs were similar in those with and without asthma (adults: 59% vs. 58%; pediatrics: 53% for both). In both subsets, the respective incidences of AEs leading to discontinuation (mostly application-site reactions) were 6.7% vs. 4.3% (adults) and 3.1% vs. 4.9% (pediatrics). Of the subjects with asthma, 60 adults (300IR: 31/179 [17%]; Placebo: 29/149 [19%]) and 29 pediatrics (300IR: 14/32 [44%]; Placebo: 15/34 [44%]) reported an AE of asthma or a related symptom during treatment. Two actively-treated participants (including one pediatric) and 9 who received placebo (including one pediatric) were administered oral corticosteroids as treatment for an AE suggestive of asthma. There were no serious drug-related AEs in any subject with asthma who received 300IR. Treatment with 5-grass pollen sublingual tablet had a similar safety and tolerability profile in adults and children whether they had or not intermittent asthma.

Efficacy of 300IR 5-Grass Pollen Sublingual Tablet in the Treatment of Rhinitis Symptoms in Polysensitized Subjects with Grass Pollen-Induced Allergic Rhinoconjunctivitis

Efficacy of 300IR 5-Grass Pollen Sublingual Tablet in the Treatment of Rhinitis Symptoms in Polysensitized Subjects with Grass Pollen-Induced Allergic Rhinoconjunctivitis

Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract

Allergen immunotherapy is an effective treatment of allergic rhinoconjunctivitis. Clinical efficacy is associated with improvement of basophil sensitivity and an increase in allergen-specific immunoglobulin concentration. We sought to determine whether changes in allergen component-specific serum IgE and IgG4 levels during the updosing phase of subcutaneous immunotherapy (SCIT) are biomarkers of the immunologic changes that can lead to treatment efficacy. Twenty-four subjects with grass pollen-induced allergic rhinoconjunctivitis were randomized 3:1 to receive SCIT (Alutard SQ) or to an open control group. IgE and IgG4 concentrations were determined for the major allergens Phl p 1 or Phl p 5 by using ImmunoCAP and for 8 grass pollen molecules by using Immuno Solid-phase Allergy Chip (ISAC) before treatment and after updosing. Levels of specific IgE against the dominant major allergens Phl p 1 and Phl p 5 increased from a mean of 23.0 to 48.8 kU/L (P=.01, n=18) during the updosing phase in ImmunoCAP measurements but decreased from a median of 4.6 ISAC specific units (ISU) to 2.14 ISU (P<.0001, n=102) when measured by using ISAC against 8 grass allergen components. The updosing phase induced a specific IgG4 level increase from a median of 0 ISU before treatment to 0.83 ISU after 12weeks (P<.0001, n=102) but only for allergen molecules to which pretreatment-specific IgE antibodies were detected (Spearman σ=0.72, P<.0001, n=102). Pretreatment allergen component-specific IgE appears to determine the induction of IgG4 in the updosing phase. Induced IgG4 seems to suppress IgE levels on ISAC, resulting in a marked decrease in ISAC-measured specific IgE levels after updosing of SCIT. Thus this decrease in ISAC IgE levels can be used to monitor the blocking effect of allergen-specific immunotherapy-induced non-IgE antibodies.

Prolonged efficacy of the 300IR 5-grass pollen tablet up to 2years after treatment cessation, as measured by a recommended daily combined score.

BackgroundThe 300IR (index of reactivity) 5-grass pollen tablet has favorable short-term and sustained clinical efficacy in patients with grass pollen-induced allergic rhinoconjunctivitis (ARC). Here, we report maintenance of efficacy and safety over 2 years following treatment discontinuation.MethodsRandomized, double-blind, placebo-controlled, parallel-group, multicenter Phase 3 trial in patients aged 18–50 years with ARC. During study years 1–3, patients received a daily sublingual tablet containing either 300IR 5-grass pollen extract or placebo, according to a discontinuous pre- and coseasonal protocol. Study years 4 and 5 were treatment-free. In response to health authorities’ recommendations, the daily combined score (DCS) was assessed in a post-hoc analysis as the efficacy endpoint. Components of the DCS were daily rhinoconjunctivitis total symptom score (DRTSS) and daily rescue medication score (DRMS).Results633 patients with ARC were randomized to placebo (n = 219) or 300IR 5-grass pollen tablet, beginning 4 months (4 M, n = 207) or 2 months (2 M, n = 207) prior to the estimated start of the grass pollen season and continuing until season’s end. During the first post-treatment year, a statistically significant difference versus placebo in least squares (LS) mean DCS was noted in patients previously receiving active treatment (300IR (2 M) point estimate: −0.16, 95% confidence interval (CI95%): [−0.26, −0.06], p = 0.0019; −31.1%; 300IR (4 M) point estimate: −0.13, CI95%: [−0.23, −0.03], p = 0.0103, −25.3%). During the second post-treatment year, patients in the 300IR (4 M) group, but not the 300IR (2 M) group, showed a statistically significant difference in LS mean DCS versus placebo (point estimate: −0.11, CI95%: [−0.21; 0.00], p = 0.0478, −28.1%). This significant efficacy seen during the post-treatment years in patients previously treated with 5-grass pollen tablet compared favorably with that during the 3 prior years of active treatment. A statistically significant difference versus placebo was also noted in secondary efficacy measures in both post-treatment years (except for DRTSS in year 5). In the absence of any active treatment, the safety profile was similar in the active groups versus placebo group during either post-treatment year.ConclusionsIn adults with grass pollen-associated ARC, 5-grass pollen tablet therapy beginning 4 months before the pollen season and continuing to season’s end demonstrated efficacy across all variables during active treatment, and this effect was prolonged for up to 2 years post-treatment.Trial registrationClinicalTrials.gov identifier: NCT00418379.

Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German

The present guideline (S2k) on allergen-specific immunotherapy (AIT) was established by the German, Austrian and Swiss professional associations for allergy in consensus with the scientific specialist societies and professional associations in the fields of otolaryngology, dermatology and venereology, pediatric and adolescent medicine, pneumology as well as a German patient organization (German Allergy and Asthma Association; Deutscher Allergie- und Asthmabund, DAAB) according to the criteria of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF).

PRS56 - Impact of Allergen Immunotherapy on Quality of Life and Health Care Costs in Adults and Children With Grass Pollen-Induced Allergic Rhinitis in Germany

• According to the World Health Organization (WHO), allergic respiratory diseases have been recognized as the fourth most important chronic disease in the world and represent a major public health problem with significant quality of life (QoL) impairment. Approximately 90 million Europeans are affected by allergic respiratory diseases. • In Germany, 25% of the adult population and 21% of the paediatric population suffer from allergic rhinoconjunctivitis (AR). • According to the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines, 10–40% of patients suffer from co-existing allergic asthma. A health economic assessment, reflective of German clinical practice, was conducted to determine the relative impact of treatment with Oralair, Grazax, ALK Depot SQ or SDT on clinical effects and healthcare costs in adults and children with moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis.

PRS52 - Impact of Allergen Immunotherapy on Symptom-Free Days and Health Care Costs in Patients With Grass Pollen-Induced Allergic Rhinitis in Germany

• According to the World Health Organization (WHO), allergic respiratory diseases respiratory diseases have been recognized as the fourth most important chronic disease in the world and represent a major public health problem with significant quality of life (QoL) impairment. Approximately 90 million Europeans are affected by allergic respiratory diseases. • In Germany, 25% of the adult population and 21% of children suffer from allergic rhinoconjunctivitis (AR). • According to the ARIA (Allergic Rhinitis and its Impact on Asthma) guidelines, 10–40% of patients suffer from co-existing allergic asthma. • Treatment of AR mainly consists of symptom control achieved by allergen avoidance or use of symptomatic drug treatment (SDT). In poorly controlled AR patients in Germany, causal treatments such as allergen immunotherapy (AIT) may be required. A health economic assessment, reflective of German clinical practice, was conducted to determine the relative impact on clinical effects, expressed as SFD, and healthcare costs when treating patients with moderate-to-severe grass polleninduced allergic rhinoconjunctivitis with Oralair® or Grazax®.

Negative clinical results from a randomised, double-blind, placebo-controlled trial evaluating the efficacy of two doses of immunologically enhanced, grass subcutaneous immunotherapy despite dose-dependent immunological response.

Specific immunotherapy is the only treatment for the underlying allergic disease in patients with respiratory allergies. The primary objective of this trial was to evaluate the efficacy and safety of two maintenance doses of immunologically enhanced, standardised quality (SQ+) grass subcutaneous immunotherapy (SCIT) [4,000 SQ+ and 15,000 SQ+; AVANZ(®) Phleum pratense (ALK)] compared with placebo. This was a randomised, double-blind, placebo-controlled, phase II/III trial. The primary evaluation was based on the combined rhinoconjunctivitis score during the entire grass pollen season. Adult subjects with grass pollen-induced allergic rhinoconjunctivitis interfering with usual activities or sleep despite symptomatic medication use, were enrolled. Four hundred and fifty subjects were randomised to receive either 4,000 SQ+ (n = 150), 15,000 SQ+ (n = 152) or placebo (n = 148). The average grass pollen exposure was 27 grains/m(3)/day. No statistically significant differences between the active groups and the placebo group were found for clinical endpoints (p > 0.05). Highly statistically significant (p < 0.001) increases in IgG4 and IgE-blocking factor were found for both active groups versus placebo. The most frequently reported adverse events were mild-to-moderate local injection-site reactions; events were generally more frequent with 15,000 SQ+ than with 4,000 SQ+ and placebo. The most common adverse events leading to premature discontinuation from the trial were anaphylactic reactions (one subject from the placebo group and five subjects from the 15,000 SQ+ group). The inconclusive results were most probably influenced by a very low grass pollen season. Other factors such as the extent of the pre-seasonal treatment could potentially have contributed. The tolerability profile was acceptable for further development.

Sublingual five-grass pollen tablets (Oralair®): a guide to their use as allergen immunotherapy for grass pollen-induced allergic rhinoconjunctivitis

Sublingual 300 IR five-grass pollen allergen extract tablets (Oralair®) are a valuable option in patients with grass-pollen induced allergic rhinoconjunctivitis. Allergen immunotherapy with sublingual five-grass pollen tablets beginning 4 months before and continuing throughout the grass pollen season reduces the symptoms of allergic rhinoconjunctivitis and the use of symptomatic rescue medications during the pollen season. Precautions should be followed to minimize the risk of systemic and local allergic reactions that may occur with allergen immunotherapy.

P85 ‐ Asthmatic children and adolescents treated in daily medical practice – results from a 2‐year sublingual allergen immunotherapy (AIT) study with grass pollen tablets

Background The aim of this non-interventional study was to document the impact of a sublingual allergen immunotherapy (AIT) with Oralair 5-grass pollen tablets (Stallergenes, France) on symptom severity (rhinitis, conjunctivitis, asthma), use of symptomatic medication and tolerability in patients with grass pollen-induced allergic rhinoconjunctivitis (RC) over 2 years of routine medical practice treatment. This poster focuses on the subgroup of asthmatic children (4-11 yrs) and adolescents (12-17 yrs).

PD14 ‐ Non‐interventional 2‐year study of sublingual immunotherapy in children and adolescents with allergic rhinoconjunctivitis caused by grass pollen

Background The aim of this non-interventional study was to document the impact of a sublingual allergen immunotherapy (AIT) with Oralair 5-grass pollen tablets (Stallergenes, France) on symptom severity, use of symptomatic medication and tolerability in patients with grass pollen-induced allergic rhinoconjunctivitis (RC) over 2 years of routine medical practice treatment. This poster focuses on the subgroups of children (4-11 yrs) and adolescents (12-17 yrs).

Sublingual solution for immunotherapy: Comparison of three different up-dosing schedules

Abstract Background Sublingual immunotherapy for treating allergic rhinoconjunctivitis represents a convenient and well-tolerated alternative to subcutaneous immunotherapy, however protocols for up-dosing prior to reaching maintenance are yet to be developed. Tolerability of three up-dosing schedules for a sublingual immunotherapy solution was evaluated. Patients and methods A parallel, multicentre trial was performed in Poland and 236 adult subjects with a clinically-relevant history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis were randomised to receive a sublingual solution of Phleum pratense (Osiris in France, SLIToneULTRA® in rest of Europe) in one of three 30-day up-dosing/maintenance schedules: the French currently used up-dosing schedule 11 days (group A, 83 subjects) and two simplified with two steps (fast 10 days and slow 20 days) schedules (group B, 73 subjects; group C, 80 subjects). Adverse events and safety were assessed. The trial was not powered to show a statistical difference between the schedules. Results Fifty-three percent of subjects reported drug-related adverse events (group A: 52%; group B: 59%; group C: 50%). The majority were mild, starting within 30 minutes after administration and lasting Conclusion Three up-dosing schedules of Phleum pratense sublingual solution showed similar tolerability profiles. A simplified up-dosing schedule is a well-tolerated alternative to the current French up-dosing schedule.