Double-blind, placebo-controlled immunotherapy with a high-molecular-weight, formalinized allergoid in grass pollen allergy

Specific immunotherapy is effective in grass pollen allergy with standardized extracts and formalinized allergoids; but systemic reactions are not uncommon. A high-molecular-weight (greater than 85,000 daltons), formalinized allergoid was investigated in a double-blind, placebo-controlled study to assess its safety and efficacy. Twenty patients received a placebo and 39 the allergoid using a rather aggressive protocol. Five patients developed a mild and transient systemic reaction with high doses of allergoid and one had a more severe reaction requiring treatment. Nasal challenges performed with orchard grass pollen grains showed that the threshold number of grains eliciting nasal symptoms was significantly (p less than 0.01) greater in the treated group. This group had significantly (p less than 0.01) less nasal symptoms during the season and specific IgG levels were significantly (p less than 0.01) elevated. There was a significant (p less than 0.01) correlation between nasal challenges and nasal symptoms during the season but no correlation between IgG and symptoms. There was no dose-dependent effect of allergoids.     

Grass pollen immunotherapy: symptomatic improvement correlates with reductions in eosinophils and IL-5 mRNA expression in the nasal mucosa during the pollen season

BACKGROUND: Tissue eosinophilia and infiltration by T(H)2-type T cells are characteristic features of allergic rhinitis both after allergen challenge and during natural allergen exposure. Specific immunotherapy inhibits allergen-induced nasal eosinophilia. OBJECTIVES: We sought to assess, in the context of a randomized trial, the relationships between symptomatic improvement after immunotherapy and eosinophil numbers and IL-5 expression in the nasal mucosa during the pollen season. METHODS: Nasal biopsy specimens were taken from 37 adults with severe summer hay fever at baseline (out of season) and at peak season after 2 years of treatment with a depot grass pollen extract or placebo. Biopsy specimens were processed for immunohistochemistry by using mAbs against eosinophils (EG2), T cells (CD3), and IL-2 receptor-positive cells (CD25), as well as for in situ hybridization by using a sulfur 35-labeled antisense riboprobe directed against IL-5. RESULTS: Immunotherapy significantly reduced symptoms (49%, P =.01) and medication requirements (80%, P =.007) compared with placebo. There was a 400% increase (P =.004) in eosinophils during the pollen season in placebo-treated patients, which was inhibited in the immunotherapy group (20% increase, P =.04 between groups). Seasonal increases were also observed for CD25(+) cells (P =.002), CD3(+) cells (P =.02), and IL-5 mRNA-expressing cells (P =.03) in the placebo group but not in the immunotherapy group. A significant correlation was observed between eosinophils and IL-5 expression (r = 0.5, P <.05). Both eosinophils (r = 0.6, P <.02) and IL-5 (r = 0.6, P <.02) correlated with symptoms after immunotherapy. CONCLUSION: Improvement in symptoms after grass pollen immunotherapy may result, at least in part, from inhibition of IL-5-dependent tissue eosinophilia during the pollen season.     

Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial

BACKGROUND: Grass pollen immunotherapy significantly reduces hay fever symptoms and medication requirements. Effects on seasonal asthma are less clear, and concerns over safety persist. OBJECTIVE: The goal of this study was to assess the effects of grass pollen immunotherapy on symptoms, bronchial hyperresponsiveness, and quality of life in seasonal rhinitis and asthma. METHODS: Forty-four patients with severe summer hay fever (of whom 36 reported seasonal chest symptoms and 28 had seasonal bronchial hyperresponsiveness) participated in a randomized, double-blind, placebo-controlled, parallel group study. After symptom monitoring for one summer, participants received injections of a depot grass pollen vaccine (n = 22) or matched placebo injections (n = 22) in a rapid updosing cluster regimen for 4 weeks, followed by monthly injections for 2 years. Outcome measures included hay fever symptoms and medication use, health-related quality of life, and measurements of nonspecific bronchial responsiveness. RESULTS: Significant reductions were observed in the immunotherapy group compared with the placebo group in hay fever symptoms (49%, 15%; P =.01), medication scores (80%, 18%; P =.007), and seasonal chest symptoms (90%, 11%; P <.05). Impairment of overall quality of life (mean score of 7 domains) during the pollen season was less in the immunotherapy group than in the placebo group (median difference [95% CI], 0.8 [0.18-1.5]; P =.02). During the pollen season there was no change in airway methacholine PC(20) (provocation concentration producing a 20% fall in FEV(1)) in the immunotherapy-treated group (P =.5), compared with an almost 3 doubling-dose decrease in the placebo-treated group (P =.01, between-group difference). There were no significant local or systemic side effects during the study. CONCLUSION: Grass pollen immunotherapy improves quality of life in seasonal allergic rhinitis and reduces seasonal asthma symptoms and bronchial hyperresponsiveness.     

Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT-study)

BACKGROUND: Children with allergic rhinitis are likely to develop asthma. OBJECTIVE: The purpose of this investigation was to determine whether specific immunotherapy can prevent the development of asthma and reduce bronchial hyperresponsiveness in children with seasonal allergic rhinoconjunctivitis. METHODS: From 6 pediatric allergy centers, 205 children aged 6 to 14 years (mean age, 10.7 years) with grass and/or birch pollen allergy but without any other clinically important allergy were randomized either to receive specific immunotherapy for 3 years or to an open control group. All subjects had moderate to severe hay fever symptoms, but at inclusion none reported asthma with need of daily treatment. Symptomatic treatment was limited to loratadine, levocabastine, sodium cromoglycate, and nasal budesonide. Asthma was evaluated clinically and by peak flow. Methacholine bronchial provocation tests were carried out during the season(s) and during the winter. RESULTS: Before the start of immunotherapy, 20% of the children had mild asthma symptoms during the pollen season(s). Among those without asthma, the actively treated children had significantly fewer asthma symptoms after 3 years as evaluated by clinical diagnosis (odds ratio, 2.52; P <.05). Methacholine bronchial provocation test results improved significant in the active group (P <.05). CONCLUSION: Immunotherapy can reduce the development of asthma in children with seasonal rhinoconjunctivitis.     

Clinical efficacy of microencapsulated timothy grass pollen extract in grass-allergic individuals.

BACKGROUND: Conventional allergen immunotherapy is clinically effective in reducing the symptoms of allergic rhinitis and asthma. It differs from other pharmacotherapies in that it can induce long-term clinical remission of these diseases. However, it requires years of treatment and is associated with serious allergic reactions. OBJECTIVE: To evaluate the safety, clinical efficacy, and immunologic mechanisms of immunotherapy with an oral, microencapsulated form of timothy grass allergen. METHODS: In this double-blind, placebo-controlled study, 24 patients aged 19 to 55 years with grass pollen allergy were randomized to receive either microencapsulated timothy grass pollen extract or placebo once a day for 10 weeks. The dose of study drug was doubled weekly. Safety was evaluated through weekly visits, daily symptom diaries, and routine laboratory tests. Efficacy was evaluated by comparing medication use and symptoms scores during peak grass pollen season before and after treatment. Allergen-specific T-cell responses, cytokine production, and IgG, IgE, and skin reactivity were measured to evaluate immunologic mechanisms. RESULTS: Eleven of 12 patients in the active treatment group had a decrease in the combined medication and symptom score, but only 4 of 10 patients in the placebo group had a decrease in scores. The proliferative response to timothy grass was reduced by at least 30% in 9 of the 12 grass-treated patients, but only 3 of 11 placebo patients had a proliferative response reduction. Timothy grass-induced interleukin-5 messenger RNA was reduced in the active group, but not in the placebo group. There were no significant changes in either group in IgG, IgE, and skin reactivity. CONCLUSIONS: Oral immunotherapy with microencapsulated allergen induces a form of immunologic tolerance to the allergen and is a safe, efficient, and effective method of allergen immunotherapy.     

A double-blind, placebo-controlled trial by the sublingual route of immunotherapy with a standardized grass pollen extract

Fifty-eight patients with well-documented history of seasonal rhinoconjunctivitis caused by grass pollens were allocated randomly on a double-blind basis to receive either sublingual therapy with a solution of purified, standardized allergen preparation (Stallergenes) or a matched placebo for 17 weeks. The assessment of the effect of oral immunotherapy, done with drops of five-grass allergen extract, was on the clinical symptoms and on the medication score of the authorized rescue treatments. The actively treated patients had significantly (P<0.05 to P<0.01) fewer symptoms of rhinitis (sneezing and rhinorrhea) and of conjunctivitis (redness and tears) during the pollen season than the placebo group. Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group (P<0.01). Side-effects were negligible. This study concludes that perlingual immunotherapy with grass pollen extract in grass-pollen-sensitive seasonal hay fever and conjunctivitis patients is effective, easy to perform, inexpensive, and safe.     

The effect of preseasonal immunotherapy on the production of histamine-releasing factor (HRF) by mononuclear cells from patients with seasonal asthma: results of a double-blind, placebo-controlled, randomized study

The effect of immunotherapy on the production of histamine-releasing factor (HRF) by mononuclear cells (MNC) from patients with seasonal asthma was investigated in a double-blind, placebo-controlled, randomized study. Twenty-four patients with asthma were randomly divided into a placebo-treated group and a grass pollen-treated group. In vitro production of HRF by MNCs and the provocative concentration of histamine that causes 20% fall in FEV1 were measured before and after immunotherapy, and symptoms were monitored during the pollen season. MNCs from the patients were either cultured alone, spontaneous HRF production (spHRF), or in the presence of grass allergens (grass-stimulated HRF production), and the supernatants were assayed for HRF activity with basophils from a single donor after the study. We found that MNCs from patients with seasonal asthma to grass pollen spontaneously produce substantial amounts of HRF. The group of patients treated with placebo developed typical symptoms in the pollen season and also an increase in HRF production. In contrast, patients treated with grass pollen demonstrated reduced symptoms and no increase in spHRF production. A high degree of correlation between spHRF productions and symptom scores in both treated groups was noted. After 2 years of immunotherapy, allergen-stimulated HRF production decreased significantly, whereas spHRF production decreased significantly only in the patients who were clinically benefitted. The change in the provocative concentration of histamine that causes 20% fall in FEV1 during the pollen season highly correlated with the change in HRF production. The results of this study suggest that HRF might be involved in the pathogenesis of atopic asthma.     

Efficacy of grass–maize pollen oral immunotherapy in patients with seasonal hay-fever: a double-blind study

Forty patients with a well-documented history of seasonal hay fever and a positive skin-prick test specific to grass pollen, including Bermuda grass and maize pollen ( Zea maize ), were allocated randomly on a double-blind basis to receive either an oral mixed grass–maize pollen extract or a matched placebo during the 1981/1982 grass pollen season. After 12 months the code was broken and patients on placebo were transferred to active therapy while patients on active therapy continued with maintenance therapy for another 12 months during the 1982/1983 grass pollen season. The assessment of the effect of the orally administered grass–maize pollen extract was on the clinical symptoms. During the first year the patients on active therapy had significantly fewer hay fever symptoms during the summer months compared with the placebo group. During the second study year, with all patients on active therapy, both groups had markedly milder symptoms compared with the placebo group. Side–effects were negligible. This study concludes that oral immunotherapy with grass-maize pollen extract in grass pollen-sensitive seasonal hay fever patients is safe and effective.     

Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis

BACKGROUND: The best way to prevent allergy symptoms is to treat the allergic condition. Specific immunotherapy with grass allergen tablets 75,000 SQ-T (Grazax, Phleum pratense, ALK-Abelló) is safe and efficacious in rhinoconjunctivitis patients. As rhinoconjunctivitis often co-exists with asthma, we aimed to confirm safety and efficacy in grass allergic subjects with asthma and rhinoconjunctivitis. METHODS: A randomized, double-blind, placebo-controlled, multicentre trial was performed 10-14 weeks prior to and during the grass pollen season 2004. About 114 subjects were randomized 2 : 1 to grass allergen tablets or placebo. The primary end points were average asthma medication and symptom scores during the grass pollen season, and secondary variables were average rhinoconjunctivitis symptom and medication scores during the grass pollen season. Additionally, number of well days was defined post hoc. RESULTS: Differences in asthma medication and symptom scores between the treatment groups were negligible. The mean difference in asthma medication score was below 0.1 and 0.3 for asthma symptom score [a single inhalation of salbutamol (200 microg) was scored 2]. No serious adverse events were reported. A reduction in rhinoconjunctivitis symptom score of 37% (P = 0.004) and a 41% (P = 0.036) reduction in medication score was found in the grass pollen season for subjects treated with the grass allergen tablet compared with placebo. Well days increased by 54% (P = 0.002). CONCLUSIONS: Self-administration of the grass allergen tablet was safe. The treatment did not impair asthma control and confirmed considerable symptom prevention and reduced medication use. It addresses the allergic condition and represents a baseline treatment for grass pollen allergy.     

IL-9 and c-Kit+ mast cells in allergic rhinitis during seasonal allergen exposure: effect of immunotherapy

Background IL-9 is an important stimulus for tissue infiltration by mast cells, a feature requiring concomitant activation of c-Kit. Objectives We assessed IL-9 expression and c-Kit + mast cells in the nasal mucosa of patients with allergic rhinitis during seasonal pollen exposure and observed the effects of allergen immunotherapy. Methods We studied 44 patients with seasonal rhinitis and asthma before and 2 years after a double-blind trial of grass pollen immunotherapy. Nasal mucosal IL-9 + cells and c-Kit + mast cells were assessed by means of immunochemistry. Cell types expressing IL-9 protein were determined by means of dual immunofluorescence. IL-9 mRNA-positive cells were assessed by means of in situ hybridization, and their phenotype was determined by using sequential immunohistochemistry and in situ hybridization. Results Nasal mucosal c-Kit + mast cells were increased during the pollen season ( P = .0001). IL-9 mRNA-positive cells also tended to increase ( P = .1) and correlated with nasal EG2 + eosinophils ( r = 0.47, P = .05) and IL-5 mRNA-positive cells ( r = 0.54, P = .02). The cell sources of IL-9 included T cells, eosinophils, neutrophils, and mast cells. When compared with placebo, successful pollen immunotherapy markedly inhibited seasonal increases in nasal mucosal c-Kit + mast cells ( P = .001) and the seasonal expression of IL-9 mRNA-positive cells ( P = .06). Immunotherapy also inhibited IL-9 protein expression from nonendothelial cell sources ( P = .0007). Conclusion IL-9 is upregulated in the nasal mucosa during the pollen season and correlates with tissue infiltration by eosinophils. Successful pollen immunotherapy is associated with inhibition of seasonal increases in both nasal c-Kit + mast cells and eosinophils. This effect might be explained, at least in part, by the reduced local expression of IL-9.     

Grass pollen immunotherapy as an effective therapy for childhood seasonal allergic asthma

BACKGROUND: Few studies have investigated the use of specific immunotherapy (SIT) for childhood seasonal allergic asthma. OBJECTIVE: We sought to examine the efficacy and safety of SIT with Alutard SQ grass pollen (Phleum pratense Alutard SQ; ALK-Abelló, H?rsholm, Denmark) in children with seasonal allergic asthma. METHODS: A randomized, double-blind, placebo-controlled study assessing the efficacy of grass pollen SIT over 2 pollen seasons was performed. Children (3-16 years) with a history of seasonal allergic asthma sensitized to grass pollen (P pratense) and requiring at least 200 microg of inhaled beclomethasone equivalent per day were enrolled. Subjects with symptomatic asthma or rhinoconjunctivitis outside the grass pollen season were excluded. The primary outcome measure was a combined asthma symptom-medication score during the second pollen season. Secondary outcome measures included end-point titration skin prick testing and conjunctival and bronchial provocation testing to allergen, sputum eosinophilia, exhaled nitric oxide, and adverse events. RESULTS: Thirty-nine subjects were enrolled. Thirty-five subjects provided data for analysis. The use of SIT was associated with a substantial reduction in asthma symptom-medication score compared with that after placebo (P = .04). There were also significant reductions in cutaneous (P = .002), conjunctival (P = .02), and bronchial (P = .01) reactivity to allergen after SIT compared with that after placebo. The 2 groups had similar levels of airway inflammation, despite a trend toward less inhaled steroid use in the active group. No serious adverse events were reported, and no subjects withdrew because of adverse events. CONCLUSION: The study has shown that SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen.     

Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid

BACKGROUND: The clinical efficacy and safety of a six-grass pollen allergoid has been studied. The advent of more exacting clinical guidelines and a better appreciation of the possible mechanisms of treatment prompted this reappraisal. METHODS: A 2-year double-blind multicentre placebo-controlled phase 3 clinical trial was undertaken in 154 patients suffering symptoms of rhinoconjunctivitis with or without asthma (GINA I or II). Therapy comprised two consecutive preseasonal short-courses of subcutaneous injections using a grass pollen allergoid adsorbed to aluminium hydroxide. RESULTS: A combined symptom and medication score (SMS) was used as the primary end-point for clinical efficacy. SMS from the first year showed a significant difference of 26.6% between the two study groups (P=0.026) and this was improved after the second year when there was a 48.4% difference in SMS between active and placebo treatment in favour of the allergoid (P = 0.018). Highly significant increases in grass pollen allergen-specific IgG1 and IgG4 antibody concentrations were measured in association with active treatment. Allergen tolerance was increased as judged by a conjunctival provocation test and significant improvements in quality of life were documented using a standardized questionnaire. The allergoid was well tolerated. CONCLUSIONS: The grass pollen allergoid was shown to be safe and clinically efficacious in the management of hay fever with or without asthma (GINA I or II).     

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.     

Double-blind, placebo-controlled study with a modified therapeutic vaccine of Salsola kali (Russian thistle) administered through use of a cluster schedule

BACKGROUND: The inhalation of Salsola kali pollen is a common cause of respiratory diseases in Europe and North America. OBJECTIVE: To evaluate the efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic vaccine of S kali. METHODS: The trial was randomized, double-blind, and placebo-controlled using a rush protocol in the build-up phase. Sixty patients with rhinoconjunctivitis (19 also had mild asthma) were randomly allocated to receive either active treatment (polymerized extract) or placebo. The final distribution was 41 patients in the active and 19 in the placebo group. Side effects were registered. Symptom and medication scores and the number of days free of symptoms during the pollen season were assessed to evaluate the clinical efficacy. A Rhinoconjunctivitis Quality of Life Questionnaire was completed in the previous pollen season (before treatment) and during the pollen season 1 year later (in the trial). Dose-response skin tests were performed at baseline and at the end of the trial. RESULTS: There was a significant difference (P < .05) in symptom and medication scores between both groups during the pollen season, with the active group the one that had fewer symptoms and lower intake of medication. The number of days without symptoms was higher in the active group (P < .05). This group also had a significant improvement in the Rhinoconjunctivitis Quality of Life Questionnaire and a reduction in skin sensitivity. No moderate or severe systemic reactions were registered. CONCLUSION: Immunotherapy with this modified vaccine of S kali pollen is safe and efficacious to treat patients clinically sensitive to this pollen. CLINICAL IMPLICATIONS: Patients allergic to S kali (Russian thistle) can be successfully treated with immunotherapy to improve symptoms of allergic rhinitis and asthma, reduce medication use, and improve quality of life parameters.     

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.     

Grass allergen tablet immunotherapy relieves individual seasonal eye and nasal symptoms, including nasal blockage

BACKGROUND: Symptoms of allergic rhinitis have a considerable impact on the quality of life of the sufferer. Sneezing, runny nose, blocked nose and headache are some of the most common symptoms of allergic rhinitis, which affects work, home and social life for many patients. Sublingual immunotherapy has shown to induce a protective immune response and provide sustained symptom prevention for allergic patients. AIMS OF THE TRIAL: The overall aims were to investigate the efficacy and safety of a sublingual grass allergen tablet (Grazax) 75 000 SQ-T; ALK-Abelló A/S, Denmark). Reported here are the effects of Grazax on individual eye and nasal symptoms. METHODS: The trial was a double-blind placebo-controlled trial including 634 participants with significant rhinoconjunctivitis because of grass pollen. Participants were randomized 1 : 1 to Grazax (a fast dissolving, once daily immunotherapy tablet for home administration) or placebo and received treatment for at least 16 weeks prior to and continuing during the grass pollen season of 2005. Four nasal symptoms and two eye symptoms were scored on a scale from 0 (no symptoms) to 3 (severe symptoms) every day during the entire grass pollen season. Nasal symptoms included runny nose, blocked nose, sneezing and itchy nose; eye symptoms included gritty feeling/red/itchy eyes and watery eyes. RESULTS: Consistent and highly significant reductions in individual eye and nasal symptoms (from 22 to 44%) were observed following treatment with Grazax as compared with placebo (P < 0.0001). CONCLUSIONS: Grazax has effects on multiple allergic symptoms, including nasal blockage, and is an effective treatment of rhinoconjunctivitis, thereby reducing the need for topical anti-allergic drugs.     

Use of glutaraldehyde-modified timothy grass pollen extract in nasal hyposensitisation treatment of hay fever.

12 patients suffering from grass pollen hay fever were treated for 14 weeks pre- and co-seasonally by intranasal self-administration of an aqueous solution of a glutaraldehyde-treated timothy grass pollen allergen. These patients had a statistically significant decrease in nasal symptom scores during the grass pollen peak period and in nasal challenge end-point titre after the season compared to placebo-treated patients. No significant effect was seen on the eye symptoms. 1 patient withdrew from the trial as a consequence of too strong local nasal reactions during treatment. Most other patients treated with active material reported mild local reactions during the first minutes after administration of the nasal spray. In the actively treated group a significant increase in serum and nasal secretion of grass pollen specific IgE, IgG and IgA antibodies was obtained during the treatment. In contrast, in the placebo group a significant increase in IgE antibody levels in serum and secretion occurred during the pollen season. The reduction in symptoms and increase in antibody production together with the simplicity of the procedure makes this approach to immunotherapy attractive.     

The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis

BACKGROUND: Binding of allergens with IgE to the IgE receptors on mast cells and basophils results in the release of inflammatory mediators as sulfidoleukotrienes (SLTs), triggering allergic cascades that result in allergic symptoms, such as asthma and rhinitis. OBJECTIVE: We sought to investigate whether anti-IgE (Oma-lizumab), a humanized monoclonal anti-IgE antibody, in addition to specific immunotherapy (SIT) affects the leukotriene pathway. METHODS: Ninety-two children (age range, 6-17 years) with sensitization to birch and grass pollens and with seasonal allergic rhinitis were included in a phase III, placebo- controlled, multicenter clinical study. All subjects were randomized to one of 4 treatment groups. Two groups subcutaneously received birch SIT and 2 groups received grass SIT for at least 14 weeks before the start of the birch pollen season. After 12 weeks of SIT titration, placebo or anti-IgE was added for 24 weeks. The primary clinical efficacy variable was symptom load (ie, the sum of daily symptom severity score and rescue medication score during pollen season). Blood samples taken at baseline and at the end of study treatment after the grass pollen season were used for separation of leukocytes in this substudy. After in vitro stimulation of the blood cells with grass and birch pollen allergens, SLT release (LTC4, LTD4, and LTE4) was quantified by using the ELISA technique. RESULTS: Before the study treatment, SLT release to birch and grass pollen exposure did not differ significantly among the 4 groups. Under treatment with anti-IgE + SIT-grass (n = 23), a lower symptom load occurred during the pollen season compared to placebo + SIT-grass (n = 24, P =.012). The same applied to both groups receiving birch SIT (n = 23 and n = 22, respectively; P =.03). At the end of treatment, the combination of anti-IgE plus grass SIT, as well as anti-IgE plus birch SIT, resulted in significantly lower SLT release after stimulation with the corresponding allergen (416 ng/L [5th-95th percentile, 1-1168] and 207 ng/L [1-860 ng/L], respectively) compared with placebo plus SIT (2490 ng/L [384-6587 ng/L], P =.001; 2489 ng/L [1-5670 ng/L], P =.001). In addition, treatment with anti-IgE was also followed by significantly lower SLT releases to the allergens unrelated to SIT (grass SIT: 300 ng/L [1-2432 ng/L] in response to birch allergen; birch SIT: 1478 ng/L [1-4593 ng/L] in response to grass pollen) in comparison with placebo (grass SIT: 1850 ng/L [1-5499 ng/L], P =.001; birch SIT: 2792 ng/L [154-5839 ng/L], P =.04]. CONCLUSION: Anti-IgE therapy reduces leukotriene release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy independent of the type of SIT allergen used.     

The co-seasonal application of anti-IgE after preseasonal specific immunotherapy decreases ocular and nasal symptom scores and rescue medication use in grass pollen allergic children

BACKGROUND: Specific immunotherapy (SIT) and treatment with anti-immunoglobulin (Ig)E antibody are complementary approaches to treat allergic rhinoconjunctivitis, which may be used for single or combined treatment. OBJECTIVE: A randomized, double-blind, placebo-controlled trial was conducted to compare the efficacy of single and combined treatment with SIT and anti-IgE (Omalizumab) in reducing symptom severity and rescue medication use. METHODS: A total of 221 subjects with birch and grass pollen allergic rhinoconjunctivitis aged 6-17 years were analysed during the grass pollen season. Group A (SITbirch + placebo) served as a reference group obtaining no effective treatment for grass pollen allergy. Group B received anti-IgE monotherapy during grass pollen season, group C SIT grass pollen monotherapy, and group D the combined treatment of SIT and Omalizumab. RESULTS: Preseasonal treatment with grass pollen SIT alone compared with SIT with the nonrelated allergen did not reduce symptoms or rescue medication use. Anti-IgE monotherapy significantly diminished rescue medication use and number of symptomatic days. The combined treatment with SIT and anti-IgE showed superior efficacy on symptom severity compared with anti-IgE alone. CONCLUSIONS: Co-seasonal Omalizumab therapy showed considerable effects in children with seasonal allergic rhinitis. The combination of SIT plus Omalizumab was clinically superior to each treatment alone during the first year of observation.     

Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract

Forty-five grass pollen-allergic patients were randomly assigned to three groups according to their skin test and RAST sensitivities and the severity of seasonal rhinitis. Eleven patients were treated with placebo (group 1), 19 patients (group 2) were treated with a six-mixed grass-pollen allergoid prepared by mild formalinization with a two-step procedure, and 15 other patients were treated with a standardized orchard grass-pollen extract (group 3). Because of a different immunotherapy schedule, only patients placed in groups 1 and 2 received the extracts in a double-blind fashion. Rush immunotherapy was performed in 3 to 6 days, and the maintenance dose was subsequently administered weekly for 4 weeks and every 2 weeks until the end of the grass-pollen season. During the season, a coseasonal treatment was administered. Systemic reactions occurred during the rush protocol in 36.8% of patients treated with allergoid and 20% of patients who received the standardized extract. Only patients treated with allergoid had systemic reactions during maintenance dose. The reactions observed with the standardized extract were more severe. Total doses of allergoid ranged from 2350 to 13,500 protein nitrogen units. Symptoms and medication scores during the peak of the season were analyzed. Patients treated with the standardized allergen had a significant reduction of the number of days of symptoms during the month of June (9.5 +/- 6.7 days; p less than 0.005) and of medication scores (1.3 +/- 1.4; p less than 0.01) compared to patients receiving placebo (19.4 +/- 8.1 days; medication score, 2.8 +/- 2.1).(ABSTRACT TRUNCATED AT 250 WORDS)