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

Background The optimal dose (300IR) of a five‐grass pollen sublingual immunotherapy tablet in terms of efficacy was previously demonstrated from the first pollen season. Objective Here, we aim to confirm whether this dose remained optimal during the peak of the pollen season by assessing the efficacy and quality of life data. Methods A total of 628 subjects with grass pollen rhinoconjunctivitis were randomized in a double‐blind, placebo‐controlled, multi‐centre, pan‐European trial. Subjects received once‐daily tablets (Stallergenes, Antony, France) of 100IR, 300IR, 500IR or placebo, starting 4 months before and throughout the 2005 grass pollen season. The pollen season was defined as the first day of 3 consecutive days with a grass pollen count above 30 grains/m³ of air, recorded using Hirst‐type volumetric pollen traps, to the last day before 3 consecutive days with a pollen count below 30 grains/m³. Results The grass pollen season lasted an average of 30 days, with a peak of 12 days. The mean treatment duration before the grass pollen season was similar in the four treatment groups (121.4±31.1 to 128.6±15.4 days in the safety population). Both the 300IR and 500IR groups had highly significant improvements in Rhinoconjunctivitis Total Symptom Score (RTSS) vs. placebo at the peak pollen season (P=0.0005 and 0.0014, respectively), which agreed with improvements in RTSS in the primary evaluations. The average RTSS scores were slightly elevated during the peak pollen season in all treatment groups. The overall Rhinoconjunctivitis Quality of Life Questionnaire score confirmed the optimal dosage 300IR at peak (P<0.0001) and at the end (P0.0031) of the pollen season. All doses were well tolerated. Conclusion At the peak pollen season, the efficacy and quality of life data for both 300IR and 500IR groups was significantly improved vs. the placebo group. These results confirm the conclusions of the primary evaluations and validate the use of 300IR tablets for clinical practice.     

Efficacy and safety of 5-grass pollen sublingual immunotherapy tablets in patients with different clinical profiles of allergic rhinoconjunctivitis

Background The optimal dose of grass pollen tablets for sublingual immunotherapy (SLIT) in allergic rhinoconjunctivitis patients was previously established in a multinational, randomized, double‐blind, placebo‐controlled study in 628 adults. Patients were randomized to receive once‐daily 5‐grass pollen sublingual tablets of 100 IR (index of reactivity), 300 IR or 500 IR, or placebo starting 4 months before the pollen season. Objective The aim of this complementary analysis was to determine whether 300 IR 5‐grass pollen SLIT‐tablets is effective in different subtypes of patients who are allergic to grass pollen. Methods Different subgroups could be identified regarding comorbidities (with or without asthma during the grass‐pollen season), sensitization (mono/polysensitization) and symptom severity. An additional exploratory analysis was performed within four subgroups based on pre‐treatment assessment: Group 1=high specific IgE; Group 2=high symptom scores; Group 3=high skin sensitivity; Group 4=any of Group 1, 2 or 3. Results Asthma and sensitization status were not significant covariates as the average Rhinoconjunctivitis Total Symptom Score (RTSS) was identical for patients with and without grass‐pollen asthma, as well as for mono‐ and polysensitized patients. Across the four subgroups, average RTSSs (± SD) for the optimal dosage (300 IR) were 3.91 ± 3.16, 3.83 ± 3.14, 2.55 ± 2.13 and 3.61 ± 2.97, for subgroups 1, 2, 3 and 4, respectively. ancova showed that in Group 1 average RTSS did not differ significantly with different doses of SLIT. In Groups 2, 3 and 4, doses of 300 IR and 500 IR were significantly more effective than 100 IR and placebo (P0.035). All doses of SLIT administered in this study can be considered safe in the patients investigated. Conclusions The risk–benefit ratio validates the use of 300 IR tablets in clinical practice in all of these patient subgroups, regardless of severity profile, sensitization status and presence of asthma.     

Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study

Background:  Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment.
Methods:  Patients (7.9–64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG₄ measured.
Results:  Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8−92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between −11.3% and −14.8% for placebo ( P  < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and −1.51% for placebo ( P  < 0.05). Combined score ( P  = 0.0508) and symptom score improvements ( P  = 0.0144) with SLIT continued during follow up. Increases in specific IgG₄ observed in the first season were sustained for SLIT vs placebo throughout treatment ( P  = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported.
Conclusions:  Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.     

Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study

Background:  Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment.
Methods:  Patients (7.9–64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG₄ measured.
Results:  Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8−92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between −11.3% and −14.8% for placebo ( P  < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and −1.51% for placebo ( P  < 0.05). Combined score ( P  = 0.0508) and symptom score improvements ( P  = 0.0144) with SLIT continued during follow up. Increases in specific IgG₄ observed in the first season were sustained for SLIT vs placebo throughout treatment ( P  = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported.
Conclusions:  Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT.     

Efficacy and safety of high-doses sublingual immunotherapy in ultra-rush scheme in children allergic to grass pollen

Background Although sublingual immunotherapy (SLIT) has been used with increasing frequency, the data on the efficacy of SLIT in pediatric asthma are limited.
Aim The aim of our study was to evaluate the efficacy and the safety of high-dose SLIT given pre-seasonally and co-seasonally in an ultra-rush scheme in children with bronchial asthma allergic to grass pollen.
Methods Fifty children with asthma, aged 6–17, sensitive to grass pollen, participated in the 2-year prospective, randomized, double-blind, placebo-controlled trial, to investigate the efficacy and safety of SLIT (Staloral 300 IR, Stallergenes SA, 25 μg major allergens) as a standardized extract of five grass pollen with ultra-rush induction.
Results SLIT significantly improved asthma symptom scores (41% vs. placebo group), reduced nasal symptoms (25% vs. placebo group) and the use of rescue medications (10% vs. placebo group), improved forced expiratory volume in 1 s, but had no effect on ocular symptoms, nasal hyper-reactivity, peak expiratory flow and forced expiratory volume between 25% and 75% of vital capacity. Serum levels of immunoglobulin E and IgG4 did not change after SLIT. After the second season of SLIT, an improvement in bronchial hyperresponsiveness was observed; however, compared with placebo, this effect was not significant. Among all subjects in SLIT group, predominantly local reactions have been recorded in 59% of subjects in the first year of treatment and in 35% in the second.
Conclusions Our study indicated that high-dose ultra-rush, co-seasonal SLIT given for 2 years, was safe and reduced a multiple symptom–medication score.     

Clinical efficacy of sublingual-swallow immunotherapy: a double-blind, olacebo-controlled trial of a standardized five-grass-pollen extract in rhinitis

Sublingual-swallow immunotherapy (SLIT) using high doses of standardized allergen extracts has been found to be effective in reducing allergic symptoms and medication needs. A double-blind, placebo-controlled study was carried out in a large number of patients to determine whether medication needs can be reduced by SLIT. Some 136 patients with grass-pollen rhinitis with or without mild asthma were studied. Patients received either placebo or SLIT with a standardized grass-pollen extract administered daily with increasing doses up to 300 IR (index of reactivity) from January to the end of July 1994. During the grass-pollen season, patients were instructed to use medications as required and to visit their doctors in case of asthma. Symptom-medications scores were assessed during the pollen season, and serum-specific IgG4 was measured before and at the end of SLIT. In the SLIT group, drug consumption dropped significantly throughout the pollen season ( P <0.02). Moreover, at the peak of the pollen season, betamethasone consumption was significantly reduced in the SLIT group ( P <0.02). Only one patient in the SLIT group had an asthma attack compared to eight patients in the placebo group ( P <0.02). IgG4 levels increased significantly in the SLIT group ( P <0.001) but without correlation with symptoms. Side-effects were comparable in both groups. This study indicates that SLIT in grass-pollen rhinitis is well tolerated, improves overall clinical symptoms, and reduces drug consumption and the need for oral corticosteroids.     

Dose dependence of immunological response to sublingual immunotherapy

BACKGROUND: Sublingual-swallow immunotherapy (SLIT) is an accepted treatment for allergic rhinitis but its optimal dosage is scantly investigated. We studied the dose dependence of clinical efficacy and immunological response to SLIT by administering two different dosages of the same allergen in rhinitic children monosensitized to grass pollen. METHODS: Seventy-one patients with comparable age and symptoms were randomized to receive SLIT by the same grass pollen extract from Stallergenes (Antony, France), 40 of them with the 100 IR and 31 with the 300 IR extract. All patients recorded diary cards for symptoms, medications and side-effects of the treatment, and had measurements of specific IgE and IgG4 in serum by the CAP System FEIA (Pharmacia, Uppsala, Sweden) and in nasal secretion by an in situ incubation method with the same reagents of CAP System FEIA. RESULTS: Symptom/medication scores during the pollen season were significantly higher in patients treated with the lower dosage compared with those treated with the 300 IR dosage. Side-effects occurred with a comparable rate (25.8%vs 27.5%) in the two groups. Serum-specific IgE and IgG4 had no significant changes after 3 months of SLIT in both groups, while a significant seasonal increase of nasal IgE (P = 0.015) and IgG4 (P = 0.019) was found only in patients treated with the lower dosage. CONCLUSIONS: A rise of specific IgG4 and a blunting of seasonal increase of specific IgE in serum was repeatedly reported during subcutaneous immunotherapy (SCIT) with pollen extracts. Our findings show such blunting of specific nasal IgE along with a low symptom/medication score in patients treated with SLIT with the higher dosage, but not a concomitant rise of specific nasal IgG4. This suggests a local immunological effect of SLIT, different from systemic mechanisms of SCIT.     

Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization

For evaluation of the efficacy and the safety of specific sublingual immunotherapy with high allergen dose, 66 children with seasonal asthma, rhinitis, and conjunctivitis due to sensitization to olive pollen were enrolled in a double-blind, randomized, placebo-controlled study between October 1994 and October 1996 in Greece. Thirty-four patients were randomly allocated to the active group, and 32 received placebo. Immunotherapy consisted of olive-allergen extracts (Stallergenes SA) administered sublingually pre- and coseasonally from January to July for 2 consecutive years. Serial concentrations from 1 to 300 IR were used up to the maintenance dose of 20 drops of 300 IR daily. The cumulative dose for each patient was 300 times higher than in parenteral immunotherapy, and the cumulative dose of the major allergen Ole e 1 was 8.1 mg/2 years. The patients were assessed by clinical parameters (symptom and medication scores from patients' daily diaries) and immunologic measurements (specific IgE. lgG4. eosinophil cationic protein [ECP]) were performed. The actively treated patients had a significantly lower score for dyspnea (P<0.04 during the first season; P<0.03 during the second season). At the poUinic peak during the second year, a lower score of conjunctivitis was recorded (P<0.05) in the actively treated patients. The analysis of intragroup evolution showed that the total score of rhinitis increased significantly during the pollinic peak in the group under placebo, whereas there was no symptomatic peak for the same period in the group under active treatment. However, the difference between the groups was not significant. The medication score did not differ significantly between the groups. Oral steroids were the only variables with a P value near the significance level (P=0.06) in favor of the actively treated group. A significant decrease in skin reactivity was recorded in the active group after 2 years of treatment. No significant variation in specific IgE and IgG4 was detected. A significantly lower level of serum ECP was observed at the pollinic peak in the actively treated patients during the first pollen season (P=0.01), but this was not confirmed the second year when the ECP levels doubled in both groups without correlation to the clinical findings. Tolerance was excellent with only a few minor side-effects reported. In conclusion, high-dose specific sublingual immunotherapy appears to be safe and effective in improving mild seasonal asthma and conjunctivitis linked to olive-pollen sensitization.     

Safety and tolerability of grass pollen tablets in sublingual immunotherapy--a phase-1 study

BACKGROUND: A single-centre, randomized, double-blind, placebo-controlled study. Aims: To compare the safety and tolerability of four different sublingual immunotherapy (SLIT) regimes in grass pollen allergic rhinitis. METHODS: Thirty subjects sensitized to grass pollen were enrolled and allocated to four groups. Sublingual immunotherapy was administered in tablets daily for 10 days. Groups 1 and 2 received incremental sublingual doses of 100, 200, 300, 400 and 500 IR, Group 1 daily and Group 2 increments every second day. Repeated constant dose regimens of 300 IR and 500 IR were administered in Groups 3 and 4 respectively. Safety assessments included adverse events (AE), vital signs, electrocardiogram (ECG) and clinical laboratory tests. RESULTS: Sublingual immunotherapy 300 IR (Group 3) administered in a constant dose and incremental doses up to 500 IR (Groups 1 and 2) were generally well tolerated. The majority of AEs were mild to moderate, the most common being oral pruritus, throat irritation and swollen tongue. Severe local AEs (swelling of throat) were observed only for Group 4. No serious systemic AEs were reported. There were no relevant changes in clinical laboratory, vital signs and ECG data. CONCLUSION: Adverse events were mostly local (sublingual), were not severe and resolved rapidly. Using a 5-day induction regimen high-dose treatment up to 500 IR could be administered without important side-effects, in contrast to initiating with a constant dose of 500 IR. The data indicate that a short dose increase phase may reduce the incidence of AEs when high-dose SLIT is administered.     

Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children

BACKGROUND: Subcutaneous immunotherapy has been the principal approach of immunotherapy in the treatment of allergic diseases. Several clinical studies with birch, alder or hazel pollen extract conducted as subcutaneous immunotherapy have been published suggesting a well-tolerated and clinically effective treatment. Only a few clinical studies of sublingual immunotherapy (SLIT) with these allergens have been published. This study investigated the clinical efficacy, safety and dose-response relationship of SLIT in children suffering from rhinoconjunctivitis with/without asthma. METHODS: Eighty-eight children (5-15 years) with a history of tree pollen-induced allergic rhinoconjunctivitis with/without seasonal asthma for >or=2 years were included. Allergy to tree pollen was confirmed by positive skin-prick test, positive specific IgE and positive conjunctival provocation test. The extract used was a glycerinated mixture of Betula verrucosa, Corylus avellana and Alnus glutinosa 100,000 SQ-U/ml. Children were randomized into three groups receiving SLIT 5 days a week for up to 18 months; dose group 1: accumulated weekly dose of 24,000 SQ-U; dose group 2: accumulated weekly dose of 200,000 SQ-U; and placebo. RESULTS: In the birch pollen season, dose group 2 showed a significant reduction of symptom (P = 0.01) and medication scores (P = 0.04) compared with placebo. Dose group 1 showed a significant reduction of symptom scores (P = 0.03). There were no statistical differences between dose groups 1 and 2. All children tolerated the treatment well. CONCLUSION: SLIT with tree pollen extract provided dose-dependent benefits in tree pollen-allergic children in terms of significantly reduced symptoms and medication use. The treatment was well tolerated.     

Sublingual immunotherapy abrogates seasonal bronchial hyperresponsiveness in children with Parietaria-induced respiratory allergy: a randomized controlled trial

BACKGROUND: The use of immunotherapy in asthmatic children is still controversial. Sublingual immunotherapy (SLIT) may represent an advance, due to the good safety profile, but little is known about its effects on lung function and nonspecific bronchial responsiveness. OBJECTIVE: The aim of this study was to assess the effects of SLIT on these parameters, in children with Parietaria pollen-induced asthma. METHODS: Thirty children with asthma solely due to Parietaria who participated in a previous randomized, placebo-controlled trial with SLIT were studied: pulmonary function test and methacholine challenge were carried out at baseline in winter 1999 (out season), during the 1999 season (before randomization), and during the 2001 season. RESULTS: Before randomization, there was a significant fall in methacholine provocation concentration during the pollen season vs baseline in both groups (SLIT group 9.78 +/- 5.95 mg/ml vs 3.37 +/- 2.99 mg/ml; placebo 8.70 +/- 6.25 mg/ml vs 2.44 +/- 2.25 mg/ml; P =.005). In the second pollen season, the response to methacholine returned to baseline values in the active group (9.10 +/- 7.7 mg/ml; P = NS vs baseline), whereas in the placebo group a significant increase in reactivity was still present (2.46 +/- 2.26; P = 0.008 vs baseline). No significant difference in FEV(1) and FEF(25-75) between the two groups was observed at all times. CONCLUSIONS: Our data show that SLIT abrogates the seasonal bronchial hyperreactivity in children with asthma due to Parietaria. This may be regarded as an indirect evidence of the effect on bronchial inflammation.     

A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen

BACKGROUND: Especially in childhood, sublingual immunotherapy (SLIT) could offer advantages over subcutaneous therapy. However, limited data on its efficacy is available. METHODS: In four German centres 97 children (age 3-14 years) with allergic rhinoconjunctivitis to grass pollen were enrolled in a prospective, double-blind trial comparing SLIT (Pangramin SLIT; ALK-SCHERAX, 0.5 microg major allergens, three times per week, 32 months) with placebo. Primary endpoint was a multiple symptom-medication score for changes in seasonal diary entries between the first and third year of the study (SLIT n=39; placebo n=38). RESULTS: The multiple symptom-medication score was significantly reduced by SLIT to 77.3% of the placebo group (P=0.0498). The subsequent analysis of the single endpoints did not reveal significant differences for symptom scores in favour of SLIT (85.1% of placebo group; P=0.22). However, the medication score improved significantly (67.1% of placebo group; P=0.0025). Furthermore, secondary endpoints assessing in vivo immune responses did not differ significantly between the groups. However, retrospective analysis showed some inhomogeneity for clinical and in vitro parameters at the beginning of the study. Allergic side effects with possible relation to the study drug were reported in both groups (SLIT 49%, placebo 27%, P=0.026). CONCLUSION: Our study indicates that SLIT had a positive effect on the reduction of a multiple symptom-medication score, mainly by significantly reducing rescue medication use, but had no significant effect on symptoms alone in children with rhinoconjunctivitis to grass pollen compared with a placebo.     

Sublingual‐swallow immunotherapy (SLIT) in patients with asthma due to house‐dust mites: a double‐blind, placebo‐controlled study

A double-blind, placebo-controlled study was carried out in 85 patients with a well-documented history of perennial asthma caused by house-dust mites. Patients received either placebo or sublingual immunotherapy (SLIT) with a standardized Dermatophagoides pteronyssinus (DP)-D. farinae (DF) 50/50 extract. After a run-in period, patients received increasing doses up to 300 IR every day for 4 weeks and then three times a week for the following 24 months. The cumulative dose was about 104000 IR, equivalent to 4.2 mg Der p 1 and 7.3 mg Der f 1. Symptom and medication scores and respiratory function were assessed throughout the trial. Serum specific IgE and IgG4 were determined before SLIT (t0) and after 6 (t1), 11 (t2), 17 (t3), and 25 months (t4) of SLIT. Mite exposure was evaluated at t0, t2, and t4 by semiquantitative guanine determinations. Patients aged 15 years and older were asked to assess their quality of life (QoL) by completing the SF20 (Short Form Health Status Survey) plus two items at t0, t2, and t4. Use of inhaled corticosteroids and beta2-agonists was significantly decreased after 25 months of treatment in both groups (P<0.03). SLIT patients showed significant improvements in respiratory function at t4 (% predicted FEV1 (P = 0.01), VC (P = 0.002), morning (P = 0.01) and evening (P = 0.03) PEFR), and reduction in daytime asthma score (P = 0.02). In the SLIT group, the post-treatment PD20 was 1.75 times higher than the baseline value. There was no change in PD20 in the placebo group. Compared to the placebo group, the SLIT group showed a significant increase in specific IgE DP(P = 0.05), IgE DF(P = 0.02), IgG4 DP(P = 0.001), and IgG4 DF (P = 0.001) levels after SLIT. QoL scores were similar in both groups at t0 and t2. At t4, all scores were better in the SLIT group than in the placebo group, with the differences being most marked for the general perception of health (P = 0.01) and physical pain (P = 0.02). Adverse events were similar in the two groups. This study shows that SLIT in house-dust-mite-related asthma has a good safety profile and improves respiratory function, bronchial hyperreactivity, and QoL.     

Prolonged preseasonal treatment phase with Grazax sublingual immunotherapy increases clinical efficacy

BACKGROUND: Sublingual immunotherapy treatment with grass allergen tablets (Grazax) is initiated preseasonally without up-dosing and treatment is continued throughout the entire grass pollen season. Aims of the study: The influence of the duration of preseasonal treatment on clinical efficacy obtained within the grass pollen season was investigated. METHODS: Data from three randomized, double-blind, placebo-controlled, multi-centre trials with varying preseasonal treatment periods were analysed. In the grass pollen season, symptom and medication score reductions relative to placebo were calculated and correlated with the duration of the preseasonal treatment period. RESULTS: The analysis was based on data from 934 patients. A significant reduction in seasonal daily rhinoconjunctivitis symptom and medication scores (17%, CI: 1-33% and 23%, CI: 1-47%, P < 0.05) was observed for patients treated with Grazax compared with placebo after approximately 8 weeks of pretreatment. The magnitude of the reductions in rhinoconjunctivitis symptom and medication scores increased with longer duration of preseasonal treatment (P < 0.0001). CONCLUSIONS: Sublingual immunotherapy with Grazax) must be initiated at least 8 weeks prior to the grass pollen season to provide a significant clinical efficacy. A longer preseasonal treatment period (>8 weeks) improves the clinical efficacy (relative to placebo) during the grass pollen season.     

Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate

BACKGROUND: Immunotherapy is a recognized treatment for allergic respiratory diseases. OBJECTIVE: To study the usefulness of immunotherapy in combination with optimal pharmacological therapy. METHODS: Thirty-eight children (8-14 years) suffering from seasonal asthma+/-rhinoconjunctivitis due to Parietaria poorly controlled by anti-allergic drugs treatment were selected. After randomization according to a double-blind placebo-controlled design they received active sublingual immunotherapy (15 children) or placebo (15 children) for 13 months combined with inhaled fluticasone twice a day during the pollen season. Eight children were taken as control, whereas all patients were instructed to take symptomatic drugs on need. Early and late skin response to the allergen were assessed in all patients before and after treatment. Drug and symptom scores, as well as visual analogue scores (VASs) and Parietaria pollen counts were assessed during the pollen season. RESULTS: Groups were well balanced for age, gender, early and late skin response before treatment. Four children dropped out, in one case in relationship with active sublingual immunotherapy (SLIT) administration. Chest and nose symptoms, as well as drug scores and VASs were significantly better in both the active or placebo SLIT+fluticasone (S+F) as compared to the control group (P between <0.001 and 0.043). Eye symptoms were significantly better in the active S+F group as compared to control (P=0.025). The VASs were significantly better in the active S+F group as compared to the placebo S+F group (P=0.037). The early skin response decreased significantly in the active S+F group (P<0.001), whereas the late skin response changed significantly in all groups, with an increase in the placebo+fluticasone group (P=0.019) and in the control group (P=0.037) and a decrease (P<0.0001) in the active S+F group. CONCLUSION: The clinical efficacy of S+F is equal to that of fluticasone alone, but the addition of SLIT has effects also on non-bronchial symptoms.     

Sublingual-swallow immunotherapy with standardized 3-grass pollen extract: a double-blind, placebo-controlled study.

BACKGROUND: Sublingual immunotherapy (SLIT) is accepted as a safe and effective route for the treatment of grass pollen allergy, but clarification of its clinical and biological efficacy requires more study. OBJECTIVE: To evaluate the efficacy, safety, and compliance of SLIT with a standardized 3-grass pollen extract in patients with grass pollen seasonal allergic rhinoconjunctivitis, with or without mild asthma. METHODS: This multicenter, randomized, double-blind study included 127 patients (aged 12-41 years; mean age, 24.9 years) with grass pollen seasonal allergic rhinoconjunctivitis, with or without mild asthma. They received either SLIT with a high-dose, standardized, 3-grass pollen extract or placebo for 10 months before and during the grass pollen season. The efficacy evaluation compared weekly clinical scores (defined as the sum of the symptom score and rescue medication score) to measure rhinoconjunctivitis and asthma for the first 8 weeks of the pollen season. We also evaluated safety and compliance and measured changes in anti-Dactylis specific IgG4 antibody levels. RESULTS: There was a trend in favor of the study group in the mean adjusted clinical score. The groups were not comparable on inclusion (P = .02): the SLIT group included more subjects with asthma and had a higher mean IgG4 serum level. Additional exploration according to subgroups with and without asthma found that among the patients without asthma, the SLIT group had a significantly better clinical score (P = .045). Anti-Dactylis specific IgG4 levels increased significantly in the SLIT group. CONCLUSION: SLIT with a standardized, high-dose, 3-grass pollen extract is safe and significantly improves the clinical score in patients with hay fever and without asthma during the pollen season.     

Serum interleukin-17 levels are related to clinical severity in allergic rhinitis

Background:  T helper (Th)-17 cells are a subset of T helper lymphocytes that exert regulatory activities. Recently, it has been reported that serum interleukin (IL)-17 levels are high in the most severe cases of birch allergy studied outside the pollen season.
Objective:  The aim of this study was to investigate a possible relationship between serum IL-17 levels and clinical parameters in patients with allergic rhinitis studied during the pollen season.
Methods:  In all, 56 patients with persistent pollen-induced allergic rhinitis were evaluated during the pollen season. Serum IL-17 levels were evaluated by enzyme-linked immunosorbent assay. Symptoms were assessed by visual analogue scale, drug use was monitored and peripheral eosinophils were counted.
Results:  Serum IL-17 levels were significantly related to clinical symptoms, drug use and peripheral eosinophil counts ( P  = 0.0001 for all).
Conclusion:  This study provides evidence that serum IL-17 level assessment might be considered to classify allergy severity.     

Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extract

Background:  Peach allergy is highly prevalent in the Mediterranean area; it is persistent and potentially severe, and therefore a prime target for immunotherapy. We aimed to study the efficacy and safety of sublingual immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3, the peach lipid transfer protein.
Methods:  Randomized, double-blind, placebo-controlled (DBPC) clinical trial. The main efficacy outcome was the change in the response to a DBPC food challenge (DBPCFC) with peach. Secondary efficacy outcomes were the changes in skin prick test (SPT), and in specific immunoglobulin E (IgE) and IgG₄ to Pru p 3. Tolerance was assessed with a careful recording of adverse events.
Results:  After 6 months of SLIT, the active group tolerated a significantly higher amount of peach (three- to ninefold), presented a significant decrease (5.3 times) in SPT, and a significant increase in IgE and IgG₄ to Pru p 3. No significant changes were observed within the placebo group. Statistically significant inter-group differences were only observed in the SPT and IgG₄ responses. No serious adverse events were reported. Systemic reactions were mild, and observed with a similar frequency in both groups. Local reactions were significantly more frequent in the active group (three times) and 95% of them restricted to the oral cavity.
Conclusion:  In this first exploratory clinical trial, SLIT for peach allergy seems to be a promising therapeutic option that could modify the clinical reactivity of the patients to peach intake and the underlying immunological response with a good tolerance.     

House-dust mite sublingual-swallow immunotherapy in perennial conjunctivitis: a double-blind, placebo-controlled study

BACKGROUND: The safety and the efficacy of sublingual-swallow immunotherapy (SLIT) in perennial conjunctivitis caused by house dust mite were evaluated in a double-blind, placebo-controlled study including 60 patients for 24 months. METHODS: Patients received either placebo or SLIT with standardized Dermatophagoides pteronyssinus (D.pt.) and D. farinae (D.f.) 50/50 extract. The evaluation of the efficacy of the SLIT was obtained by using standardized D. pteronyssinus (D.pt.) extracts on the antigen-specific conjunctival provocation test (CPT). Specific CPT, skin sensitivity and serum-specific IgE were performed before starting treatment and 6, 12, 18 and 24 months. RESULTS: Of the 60 patients included, only 45 completed the study (26 in the active group and 19 in the placebo group, P < 0.05). Two out of 30 (6.6%) patients dropped out because of insufficient efficacy in the active group compared to eight out of 30 (26.6%) in the placebo group (P < 0.05). There was a significant increase in the antigen threshold required to obtain a positive CPT from 8.2 IR [95% confidence interval (CI) 5.9-11.4] at baseline to 21.7 IR (95% CI 15.4-30.4) at 2 years (M24) in the active group, compared to 8.1 IR (95% CI 5.4-12.1) at baseline to 8.1 IR (95% CI 5.1-12.4) at M24 in the placebo group (P < 0.04 for overall treatment difference, P < 10-7 for the time-treatment interaction; repeated measures ANOVA). Differences between groups at individual time points were significant from 18 months on. Despite increased antigen concentrations, CPT scores were lower overall in the active than in the placebo group (P < 0.001). No serious adverse effects were reported. CONCLUSION: SLIT effectively increased the antigenic threshold required to obtain a positive CPT to house-dust mite antigen. Tolerance to and innocuity of SLIT were comparable to previous studies. This could justify recommending SLIT for the preventive treatment of perennial conjunctivitis caused by house dust mites.     

Short course of grass allergen peptides immunotherapy over 3 weeks reduces seasonal symptoms in allergic rhinoconjunctivitis with/without asthma: A randomized,multicenter, double‐blind,placebo‐controlled trial

Background

Immunotherapy with peptide hydrolysates from Lolium perenne (LPP) is an alternative treatment for seasonal allergic rhinitis with or without asthma. The aim of this study was to assess the clinical efficacy and safety of a cumulative dose of 170 μg LPP administered subcutaneously over 3 weeks.

Methods

In a randomized, double‐blind, placebo‐controlled trial, 554 adults with grass pollen rhinoconjunctivitis were randomized (1:2 ratio) to receive 8 subcutaneous injections of placebo or 170 μg LPP administered in increasing doses in 4 visits over 3 weeks. The primary outcome was the combined symptom and medication score (CSMS) measured over the peak pollen season. Reactivity to conjunctival provocation test (CPT) and quality of life (QOL) was assessed as secondary endpoints.

Results

The mean reduction in CSMS in the LPP vs placebo group was ?15.5% (P = .041) during the peak period and ?17.9% (P = .029) over the entire pollen season. LPP‐treated group had a reduced reactivity to CPT (P < .001) and, during the pollen season, a lower rhinoconjunctivitis QOL global score (P = .005) compared with placebo group. Mostly mild and WAO grade 1 early systemic reaction (ESR) were observed ≤30 minutes in 10.5% of LPP‐treated patients, whereas 3 patients with a medical history of asthma (<1%) experienced a serious ESR that resolved with rescue medication.

Conclusion

Lolium perenne pollen peptides administered over 3 weeks before the grass pollen season significantly reduced seasonal symptoms and was generally safe and well‐tolerated.