Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis

BACKGROUND: Specific immunotherapy is the only treatment modality that has the potential to alter the natural course of allergic diseases. Sublingual immunotherapy has been developed to facilitate access to this form of treatment and to minimize serious adverse events. OBJECTIVE: To investigate the efficacy and safety of sublingual grass allergen tablets in seasonal allergic rhinoconjunctivitis. METHODS: A multinational, multicenter, randomized, placebo-controlled trial conducted during 2002 and 2003. Fifty-five centers in 8 countries included 855 participants age 18 to 65 years who gave a history of grass pollen-induced allergic rhinoconjunctivitis and had a positive skin prick test and elevated serum allergen-specific IgE to Phleum pratense. Participants were randomized to 2500, 25,000, or 75,000 SQ-T grass allergen tablets (GRAZAX; ALK-Abelló, H?rsholm, Denmark) or placebo for sublingual administration once daily. Mean duration of treatment was 18 weeks. RESULTS: Average rhinoconjunctivitis scores during the season showed moderate reductions of symptoms (16%) and medication use (28%) for the grass allergen tablet 75,000 SQ-T (P = .0710; P = .0470) compared with placebo. Significantly better rhinoconjunctivitis quality of life scores (P = .006) and an increased number of well days (P = .041) were also observed. Efficacy was increased in the subgroup of patients who completed the recommended preseasonal treatment of at least 8 weeks before the grass pollen season (symptoms, 21%, P = .0020; and medication use, 29%, P = .0120). No safety concerns were observed. CONCLUSION: This study confirms dose-dependent efficacy of the grass allergen tablet. Although further studies are required, the greater tolerability of the tablet may permit immunotherapy to be available to a much broader group of patients with impaired quality of life caused by grass pollen allergy. CLINICAL IMPLICATIONS: For patients with grass pollen allergy, sublingual immunotherapy is well tolerated and can reduce symptoms and improve quality of life.     

Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis

BACKGROUND: Allergen immunotherapy (desensitization) by injection is effective for seasonal allergic rhinitis and has been shown to induce long-term disease remission. The sublingual route also has potential, although definitive evidence from large randomized controlled trials has been lacking. OBJECTIVE: The aim was to confirm the efficacy of a rapidly dissolving grass allergen tablet (GRAZAX, ALK-Abelló, H?rsholm, Denmark) compared with placebo in patients with seasonal rhinoconjunctivitis. METHODS: A longitudinal, double-blind, placebo-controlled, parallel-group study that included 51 centers from 8 countries. Subjects were randomized (1:1) to receive a grass allergen tablet or placebo once daily. A total of 634 subjects with a history of grass pollen-induced rhinoconjunctivitis for at least 2 years and confirmation of IgE sensitivity (positive skin prick test and serum-specific IgE) were included in the study. Subjects commenced treatment at least 16 weeks before the grass pollen season, and treatment was continued throughout the entire season. RESULTS: The primary efficacy analysis showed a reduction of 30% in rhinoconjunctivitis symptom score (P < .0001) and a reduction of 38% in rhinoconjunctivitis medication score (P < .0001) compared with placebo. Side effects mainly comprised mild itching and swelling in the mouth that was in general well tolerated and led to treatment withdrawal in less than 4% of participants. There were no serious local side effects and no severe systemic adverse events. CONCLUSION: Sublingual immunotherapy with grass allergen tablets was effective in grass pollen-induced rhinoconjunctivitis. The tablet was well tolerated with minor local side effects. CLINICAL IMPLICATIONS: The grass allergen tablet represents a safe alternative to injection immunotherapy suitable for home use.     

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.     

Efficacy and safety of specific immunotherapy with a high-dose sublingual grass pollen preparation: a double-blind, placebo-controlled trial.

BACKGROUND: Sublingual immunotherapy (SLIT) is increasingly being used for the treatment of allergic rhinitis, but there are conflicting study results demonstrating clinically relevant efficacy. OBJECTIVE: To show clinical efficacy and safety of a new high-dose grass pollen preparation for SLIT. METHODS: In a 2-year, double-blind, placebo-controlled trial, 185 subjects with rhinitis or rhinoconjunctivitis, with or without asthma, were treated with a recently developed, high-dose, 6-grass pollen mixture for SLIT once daily. RESULTS: The primary end point, a combined symptom-medication score, showed almost no change in the placebo group during a 42-day evaluation period in the grass pollen season from 2003 to 2005, whereas active treatment was associated with a significant and clinically relevant improvement (full analysis set, P = .01; main data set, P = .002). The effect was irrespective of asthma diagnosis. Allergen-specific IgE showed no difference in both groups, and specific IgG4 and IgG1 increased with active treatment in the first and second study years compared with placebo, clearly indicating the immunogenic effect of the active treatment. The SLIT was well tolerated. No serious adverse drug reactions occurred. CONCLUSIONS: High-dose, sublingual, specific immunotherapy with an extract of a 6-grass pollen mixture showed a significant and clinically relevant improvement in subjects with grass pollen-associated rhinitis or rhinoconjunctivitis, with or without asthma. The treatment with the sublingual solution was well tolerated.     

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.     

Sublingual immunotherapy: a double‐blind, placebo‐controlled trial with Parietaria judaica extract standardized in mass units in patients with rhinoconjunctivitis, asthma, or both

BACKGROUND: New routes of administering immunotherapy in respiratory allergy are being studied as an alternative to conventional injective immunotherapy. We carried out a study to evaluate the clinical efficacy and effects of sublingual immunotherapy in patients with Parietaria judaica-induced respiratory allergy. METHODS: A double-blind, placebo-controlled design was followed. Thirty patients with P. judaica rhinoconjunctivitis, mild asthma, or both were randomly chosen for sublingual immunotherapy (14 patients) or placebo treatment (16 patients). The patients underwent preseasonal rush induction treatment followed by coseasonal maintenance treatment during the Parietaria pollen season. Symptom and drug scores, as well as specific IgE and specific IgG4, were recorded. RESULTS: Significantly lower symptom and drug scores were found (P=0.04), especially during the Parietaria pollination period, in the immunotherapy group. No significant difference in specific IgE and specific IgG4 was detected between the active and placebo groups; a statistically significant increase of specific IgE was detected in both groups (P=0.05). No patient undergoing active sublingual immunotherapy reported local or systemic side-effects. CONCLUSIONS: Our data suggest that sublingual immunotherapy is both clinically effective and safe in treating patients with Parietaria-induced rhinoconjunctivitis and mild asthma.     

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.     

Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care

BACKGROUND: Sublingual immunotherapy (SLIT) is considered safer and more convenient than subcutaneous therapy and therefore has been proposed as especially suitable for children and in primary care. Most efficacy studies in children lack power to be conclusive, and all have been performed in referral centers. OBJECTIVE: To investigate the efficacy of SLIT with grass pollen allergen in children and adolescents with rhinoconjunctivitis in a primary care setting. METHODS: Youngsters aged 6-18 years with hay fever were enrolled from general practices and randomly assigned to receive placebo or grass pollen mix for 2 years. The primary outcome was the mean daily total symptom score (scale 0-15) comprising sneezing, itching nose, watery running nose, nasal blockage, and itching eyes during the months May-August of the second treatment year. RESULTS: Out of 204 youngsters randomized, 168 entered the intention-to-treat analysis (91 verum, 77 placebo). The mean daily total symptom score did not differ between participants allocated to verum and those allocated to placebo (difference for verum minus placebo: -0.08, 95%CI, -0.66-0.50; P = .78). No differences were found for rescue medication-free days, disease-specific quality of life, and overall evaluation of the treatment effect. Local side effects were more frequent in the verum group (39% vs 17% of participants; P = .001). CONCLUSION: Sublingual immunotherapy with grass pollen in a primary care setting is not effective in children and adolescents. CLINICAL IMPLICATIONS: Currently, SLIT cannot be recommended for general practitioners as a therapeutic modality in youngsters with grass pollen allergy.     

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-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 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 of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: a double-blind placebo-controlled study

BACKGROUND: Local application of allergen extracts in specific immunotherapy is accompanied by increased compliance and significantly reduced side effects. However, efficacy of local immunotherapy in children has yet not been sufficiently demonstrated. This study was performed to determine clinical efficacy of high dose sublingual swallow immunotherapy (SLIT) by a double-blind placebo-controlled study in children with grass pollen allergy using high dose allergen extracts. METHODS: A total of 161 children with seasonal rhinoconjunctivitis of which, 68 had also asthma symptoms were enrolled in a multicenter double-blind placebo-controlled study for 1 year and treated on a daily basis with sublingually applied allergen drops. After 1 year all children were given treatment for another 2 years in an open-controlled setting. Symptom scores and medication were assessed during the pollen seasons with structured interviews. Applied allergen dosage, compliance, and side effects were documented by daily diary cards. Primary endpoint was a clinical index (CI) combining symptom scores with medication index. Titrated skin prick tests (SPT) and specific antibody measurements were performed each year. RESULTS: Combining symptom with medication scores to CI was highly reliable (reliability coefficient = 0.89, standard error = 9.6%). Allergen-specific IgE- and IgG-subclass antibodies increased significantly in patients treated with SLIT indicating an activation of the immune response induced by the locally applied grass pollen extract. SPT reactivity did not change during therapy. After 1 year of SLIT in the original design we observed no significant difference in the CI between treatment and placebo analyzing all patients included in the study per intention to treat and per protocol. However, subgroup analysis in a repeated measures model revealed that patients with SLIT and severe symptoms before the beginning of treatment (CI > mean/ > 1.51) showed a significant improvement of clinical symptoms after 3 years. CONCLUSION: In this study SLIT was accompanied by a significant placebo effect. Efficacy of treatment could only be seen in children with severe clinical symptoms and this became clinically marked after 3 years of therapy.     

Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial

BACKGROUND: We assessed the efficacy of preseasonal local allergoid immunotherapy in a group of children with asthma and/or rhinitis and/or rhinoconjunctivitis due to grass pollen. METHODS: We randomly assigned 24 children allergic to grass pollen to receive local allergoid immunotherapy for 3 months before the pollen season and 24 such patients to receive identically appearing placebo. The immunotherapy consisted of tablets of monomeric allergoid grass pollen allergens held in the mouth until they dissolved and then swallowed. The study was double-blind. Symptoms and medications were scored on diary cards during the pollen season. Nasal eosinophil cationic protein levels were measured by the monoclonal antibodies EG1 and EG2 outside the pollen season and at low and at high pollen concentration during the pollen season. RESULTS: The active-treatment group had a statistically significant reduction of total symptoms (P<0.05), especially bronchial symptoms (P<0.05), in comparison with the placebo group. Immunotherapy was well tolerated and compliance was good. Nasal levels of EG2 and EG1 increased significantly during the pollen season, but there was no difference between groups. EG2/EG1 increased significantly only in the placebo group during natural allergen exposure (P<0.01). CONCLUSIONS: Our results suggest that this immunotherapy is effective for the treatment of asthma due to grass pollen in children.     

The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study

BACKGROUND: There is only very limited documentation of the efficacy and safety of high-dose subcutaneous birch pollen immunotherapy (IT) in double-blind, placebo-controlled (DBPC) studies. Birch pollen is a major cause of allergic morbidity in northern Europe and in eastern parts of North America. METHODS: Thirty-five patients with severe rhinoconjunctivitis (hay fever) to birch pollen were allocated to double-blinded clustered IT with a depot birch pollen extract (Betula verrucosa) or placebo injections. Seven patients in each group had concomitant self-reported seasonal asthma. Treatment was conducted as a clustered regimen and was performed in a specialist unit. Symptom scores from nose, eyes, and lungs, and use of oral and topical antihistamines, beta-2-agonists, and oral corticosteroids were recorded daily during the season of 2000. Sensitivity to allergen provocation in skin, conjunctiva, and nasal mucosa was measured before and after 10 months of treatment. Post-seasonal assessment of symptom severity was performed using a simple questionnaire. RESULTS: IT reduced the symptom score for both rhinoconjunctivitis and asthma (P-values < 0.05), total medication score (P < 0.02) and use of oral antihistamines (P < 0.01). IT reduced specific conjunctival sensitivity (P < 0.05), skin prick test, and especially cutaneous late-phase response diameters (P < 0.00001), and increased general well-being on post-seasonal evaluation (P < 0.01). IT was safe, with side-effects at the same level as placebo. CONCLUSIONS: High-dose, subcutaneous IT is efficacious and safe in patients with severe birch pollen rhinoconjunctivitis and asthma.     

A double-blind placebo-controlled evaluation of sublingual immunotherapy with a standardized ragweed extract in patients with seasonal rhinitis. Evidence for a dose-response relationship

BACKGROUND: There is a growing consensus on the benefits of sublingual-swallow immunotherapy in the treatment of allergic diseases. METHODS: This randomized, double-blind placebo-controlled study was undertaken to assess the efficacy and safety of sublingual immunotherapy with standardized ragweed pollen extract tablets, in patients with an allergic rhinitis. A total of 110 outpatients were randomized (immunotherapy [I]: 55; placebo [P]: 55), of whom 99 were analyzable for efficacy (I: 48; P: 51) and 106 analyzable for safety (I: 53; P: 53). After a 28-day progression phase, the patients received a maintenance treatment during 6.5 months. Efficacy variables included a global assessment of efficacy (patient/ investigator), symptoms and medication scores as well as the frequency of asthma attacks. RESULTS: In the active treatment group, 43 patients completed the study, versus 49 on placebo. During the whole period of pollination, the difference favoring immunotherapy was highly significant for the global assessment by the patient (p = 0.004) and by the investigator (p = 0.005). Adverse reactions were reported more often in the active treatment but mild or moderate, and they abated after dose adjustment. A subgroup analysis of those patients receiving the highest dose of immunotherapy (3 tablets 3 times a week) showed a highly significant response for rhinitis and conjunctivitis total scores by comparison to lower dosages. CONCLUSION: This study confirms the efficacy and safety of sublingual immunotherapy and strongly suggests a dose-response relationship.     

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.     

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.     

Allergy immunotherapy tablet: Grazax® for the treatment of grass pollen allergy

Immunotherapy is the only treatment for allergy that alters the natural course of this disease. Sublingual immunotherapy has been developed to make immunotherapy more suitable for allergic patients. In the largest clinical program ever conducted with grass allergen-specific immunotherapy, over 2000 adults and more than 500 children have been exposed to Grazax(?) (ALK-Abello A/S, Hoersholm, Denmark). Grazax is an oral lyophilisate tablet (allergy immunotherapy tablet [AIT]) for sublingual administration, containing 75,000 standardized quality tablet units of allergen extract of grass pollen (Phleum pratense). Grazax is indicated for treatment of grass pollen-induced rhinitis and conjunctivitis in adult and pediatric patients. Results from the GT-08 trial (first, second and third treatment years) showed a reduction of 31, 36 and 29%, respectively, in symptom scores and a reduction of 38, 45 and 40% of medication scores, respectively, compared with placebo. Subjects treated with Grazax also had an increased number of well days and a relevant improvement in quality of life. More subjects experienced excellent and complete rhinoconjunctivitis control in comparison with patients treated with symptomatic medications only. Grazax treatment is also associated with a sustained and relevant increase of specific IgG4. This increase is also observed after stopping AIT treatment. The most common adverse events related to Grazax treatment are local reactions, such as oral itch, edema of the mouth, ear pruritus, throat irritation and sneezing. Clinical efficacy of Grazax is observed also after 1 and 2 years of follow-up after stopping the AIT treatment. Grazax is efficacious and safe for treatment of grass-pollen rhinoconjunctivitis in both adults and children. Grazax is the first AIT showing a disease-modifying effect on grass pollen-induced allergic rhinoconjuctivitis.     

Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen extract in seasonal indigenous cypress pollen rhinoconjunctivitis. A double-blind, placebo-controlled study

BACKGROUND: The efficacy of standardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens. METHODS: Forty adults with European cypress-allergic rhinoconjunctivitis were randomized to receive immunotherapy or a matched placebo. Specific immunotherapy was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point score. RESULTS: Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001; 14 in each group completed year 2002. A statistically significant improvement (41%, p < 0.02) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was not significant. This significant improvement was greater at the peak of the 2002 pollen season (63%, p < 0.01). CONCLUSIONS: This study therefore indirectly validates the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted.     

Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis

Allergic rhinitis is a common condition which, at its most severe, can significantly impair quality of life despite optimal treatment with antihistamines and topical nasal corticosteroids. Allergen injection immunotherapy significantly reduces symptoms and medication requirements in allergic rhinitis but its use is limited by the possibility of severe systemic reactions. There has therefore been considerable interest in alternative routes for delivery of allergen immunotherapy, particularly the sublingual route. The objective was to evaluate the efficacy of sublingual immunotherapy (SLIT), compared with placebo, for reductions in symptoms and medication requirements. The Cochrane Controlled Clinical Trials Register, MEDLINE (1966-2002), EMBASE (1974-2002) and Scisearch were searched, up to September 2002, using the terms (Rhin* OR hay fever) AND (immunotherap* OR desensiti*ation) AND (sublingual). All studies identified by the searches were assessed by the reviewers to identify Randomized Controlled Trials involving participants with symptoms of allergic rhinitis and proven allergen sensitivity, treated with SLIT or corresponding placebo. Data from identified studies was abstracted onto a standard extraction sheet and subsequently entered into RevMan 4.1. Analysis was performed by the method of standardized mean differences (SMD) using a random effects model. P-values < 0.05 were considered statistically significant. Subgroup analyses were performed according to the type of allergen administered, the age of participants and the duration of treatment. Twenty-two trials involving 979 patients, were included. There were six trials of SLIT for house dust mite allergy, five for grass pollen, five for parietaria, two for olive and one each for, ragweed, cat, tree and cupressus. Five studies enrolled exclusively children. Seventeen studies administered the allergen by sublingual drops subsequently swallowed, three by drops subsequently spat out and two by sublingual tablets. Eight studies involved treatment for less than 6 months, 10 studies for 6-12 months and four studies for greater than 12 months. All included studies were double-blind placebo-controlled trials of parallell group design. Concealment of treatment allocation was considered adequate in all studies and the use of identical placebo preparations was almost universal. There was significant heterogeneity, most likely due to widely differing scoring systems between studies, for most comparisons. Overall there was a significant reduction in both symptoms (SMD -0.42, 95% confidence interval -0.69 to -0.15; P = 0.002) and medication requirements [SMD -0.43 (-0.63, -0.23); P = 0.00003] following immunotherapy. Subgroup analyses failed to identify a disproportionate benefit of treatment according to the allergen administered. There was no significant reduction in symptoms and medication scores in those studies involving only children but total numbers of participants was too small to make this a reliable conclusion. Increasing duration of treatment does not clearly increase efficacy. The total dose of allergen administered may be important but insufficient data was available to analyse this factor.