Safety and efficacy of Juniperus ashei sublingual-swallow ultra-rush pollen immunotherapy in cypress rhinoconjunctivitis. A double-blind, placebo-controlled study

BACKGROUND: The safety and efficacy of high-dose sublingual-swallow immunotherapy (SLIT) has been established in pollen rhinoconjunctivitis. This treatment has now been evaluated using an ultra-rush incremental dose regimen with a Juniperus ashei allergen extract in patients allergic to Cupressus sempervirens and Cupressus arizonica. METHODS: Patients received either placebo or SLIT. Evaluation of safety was based on the frequency of adverse events during the incremental dose period (half a day) and during maintenance therapy (4 months). Evaluation of efficacy was based on symptom and medication scores at the pollen peak. RESULTS: Seventy of the 76 patients included completed the study. There were no drop-outs during the rush procedure. One patient in the active group dropped out during the maintenance therapy due to adverse events: gastric pain and vomiting. There was also 1 drop-out in the placebo group due to pregnancy. Adverse events were infrequent, local and mild. Symptom scores for rhinitis and conjunctivitis were not statistically different between groups, but there was a marked and significant (p < 0.03) decrease of the medication score (about 50%) and nasal steroid consumption (about 75%) in the active treatment group. An increase from baseline of serum IgE and IgG4 J. ashei-specific antibodies was only observed in actively treated patients (p < 0.04 and p < 0.01, respectively). CONCLUSIONS: The tolerability and safety of high-dose ultra-rush SLIT were comparable to those reported in previous SLIT studies. SLIT with J. ashei extract, due to its high Jun a 1 content, significantly reduced nasal steroid consumption in patients allergic to European cypress.     

Immunotherapy with a calcium phosphate-adsorbed five-grass-pollen extract in seasonal rhinoconjunctivitis: a double-blind, placebo-controlled study

BACKGROUND: Calcium phosphate-adsorbed allergen extracts are used for subcutaneous immunotherapy to avoid the use of aluminium adjuvants. OBJECTIVES: A double-blind, placebo-controlled study was performed in order to confirm the safety and assess the efficacy of a standardized five-grass-pollen extract adsorbed onto calcium phosphate for specific immunotherapy (IT). METHODS: Twenty-nine patients with seasonal rhinoconjunctivitis were randomized to receive either the active preparation (16 patients) or placebo (13 patients), in a 1-year study. During the increasing dose phase, an extract ranging from 0.1 IR per ml to 50 IR per ml was administered at a rate of one subcutaneous injection per week until a maintenance dose was reached. The patients were assessed by symptom diary and rescue medications during seasonal exposure and specific nasal and skin reactivity before and after IT. Immunological parameters (specific IgE and IgG4 antibodies) were assessed before, during and after IT. RESULTS: The overall symptoms score (mean AUC) was not significantly different between the IT group and the placebo group during grass-pollen exposure (49.6 vs. 56, respectively). The total medication score (mean AUC) was significantly lower in the IT group than in the placebo group (11 vs. 41, P < 0.01, Mann-Whitney U-test). The cumulative symptom/medication score was significantly lower in the IT group than in the placebo group (64.5 vs. 102.3, P < 0.05, U-test). A significant increase in nasal reactivity threshold was observed after IT in the IT group (21. 4 IR/mL before IT vs. 63.4 IR/mL after IT, P < 0.01, Wilcoxon), whereas no significant changes were observed in the placebo group (31.0 IR/mL before IT vs. 37.7 IR/mL after IT). IT induced a significant reduction in grass pollen cutaneous reactivity in the actively treated group (P < 0.001). A significant increase in serum-specific IgG4 antibody response was observed in the IT group (3.1% before IT vs. 10.1% after IT, P < 0.001). Nine patients in the IT group developed moderate immediate systemic reactions vs. two patients in the placebo group. CONCLUSION: Specific immunotherapy with calcium phosphate-adsorbed standardized grass pollen extract was safe and effective for the treatment of patients with seasonal allergic rhinoconjunctivitis.     

Diagnosis of cypress pollen allergy: in vivo and in vitro standardization of a Juniperus ashei pollen extract

BACKGROUND: Cypress pollen allergy is a major cause of rhinoconjunctivitis and asthma in the Mediterranean area. The nonstandardized cypress allergen extracts currently available for the diagnosis of cypress allergy have a low level of activity. The search for an active material has led to the selection of Juniperus ashei (Ja) pollen because of its very high cross-reactivity with cypress extracts and its superior allergenic activity. The aim of this study was to characterize in vitro and calibrate in vivo an in-house reference extract (IHRS) of J. ashei pollen and determine the specificity and sensitivity of a standardized Ja extract for the prick test diagnosis of cypress allergy. METHODS: Juniperus ashei pollen extract was analysed by 2-D electrophoresis. The IHRS Ja extract was calibrated by skin prick testing in 28 cypress-allergic patients. The sensitivity and specificity of cypress allergy diagnosis using a standardized Ja extract was studied by skin prick test in 42 cypress-allergic patients and 53 nonallergic patients. Jun a 1 content of the IHRS was determined by a monoclonal antibody-based electrophoretic technique. RESULTS: The Jun a 1 content of the 100 IR/ml Ja IHRS extract was 180 microg/ml. For in vivo diagnosis of cypress allergy, Ja pollen extract demonstrated a sensitivity of 95%, a specificity of 100%, a negative predictive value of 96%, and a positive predictive value of 100%. CONCLUSION: Standardized Ja pollen extract is therefore a very appropriate tool for the in vivo diagnosis of cypress pollen allergy and good candidate for specific immunotherapy.     

Immunotherapy with mosquito (Culex quinquefasciatus) extract: a double-blind, placebo-controlled study.

BACKGROUND: Mosquito allergy is well established, but mosquito immunotherapy requires validation using clinical and immunologic variables. OBJECTIVE: To evaluate the tolerability and efficacy of specific immunotherapy with Culex quinquefasciatus (mosquito) extract. METHODS: We performed a randomized, double-blind, placebo-controlled trial of immunotherapy for 1 year in 40 patients with asthma, rhinitis, or both. Patients were evaluated by means of intradermal testing, symptom and drug scores, and histamine provocation testing before and after 1 year of immunotherapy. Mosquito specific IgE and IgG subclass antibody responses were evaluated at the basal level and after 1 year. RESULTS: Patients receiving allergen immunotherapy for 1 year showed a significant improvement compared with baseline and patients receiving placebo regarding skin reactions, symptom scores (rhinitis and asthma), and forced expiratory volume in 1 second. Provocation concentration of histamine that caused a decrease in forced expiratory volume in 1 second of 20% by inhalation was elevated in the group receiving immunotherapy. In the active group serologic analysis showed a slight reduction in IgE levels (P = .02) but a significant elevation in IgG4 levels (P = .001), with a significant decrease in the IgE/IgG4 ratio (P = .001). All these changes in the placebo group were nonsignificant. CONCLUSIONS: Allergen immunotherapy with mosquito extract was well tolerated, with improvement in symptoms and airway reactivity. Good clinical outcome was associated with increased IgG4 antibody levels.     

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.     

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.     

Immunotherapy with a modified birch pollen extract in allergic rhinoconjunctivitis: clinical and immunological effects

Background Modification of allergens by glutaraldehyde in extracts used for immunotherapy reduces the risk for side‐effects, but the therapeutic efficacy of such extracts still requires further evaluation. The aim of this study was to show the efficacy and safety of immunotherapy with a single‐strength glutaraldehyde‐modified aluminium hydroxide‐adsorbed extract of birch pollen. Methods In a multi‐centre, randomized, placebo‐controlled double‐blind setting, starting in 2001 between 1 August and 15 December, birch pollen‐allergic subjects (n=62) were injected subcutaneously with increasing doses of the allergen extract or placebo at weekly intervals over a 6‐week period (or longer if adverse reactions occurred). Maintenance dose was given monthly for at least 18 months till June 2003. Efficacy was evaluated on the basis of the clinical index score (CIS), a combined symptom and medication score. Results Fifty‐eight patients could be evaluated for clinical efficacy. Treatment with the birch pollen extract resulted in a lower CIS for the eye and nose during the peak birch pollen season of 2003, compared with placebo (reductions of 42% and 31%, respectively) (P=0.017 and 0.039). Active treatment induced IgG and IgG4 antibodies reacting with Bet v 1 (P<0.001). Sera from treated patients had a blocking effect on Bet v 1‐induced basophil activation (P<0.04). No major adverse reactions occurred, and local reactions, if occurring, were mild. Conclusion Immunotherapy with a modified slow‐release birch pollen extract, administered in a single‐strength preparation with a rapid dose increase, is safe and efficacious. IgG and IgG4 antibodies against native Bet v 1 are induced, which block basophil activation.     

A double-blind,placebo-controlled immunotherapy dose-response study with standardized cat extract

BACKGROUND: Allergen immunotherapy with doses of cat extract containing approximately 15 microg of the major allergen, Fel d 1, have been proved clinically effective in several double-blind, placebo-controlled studies. However, the maintenance doses used in allergy practice in the United States are often considerably less than this proven dose. OBJECTIVE: The purpose of this investigation was to determine whether maintenance immunotherapy with cat dander extract containing 0.6 microg or 3.0 microg of Fel d 1 was more effective than placebo and similar in efficacy to treatment with extracts containing 15.0 microg Fel d 1, immunologic parameters being used as the outcome. METHODS: Twenty-eight cat-allergic patients were randomly entered, 7 in each group, into a double-blind, placebo-controlled comparison of the immunologic response to treatment with placebo or cat dander extract containing 0.6 microg, 3.0 microg, or 15.0 microg of Fel d 1. Maintenance doses were achieved in 8 visits over a period of 4 weeks through use of a cluster regimen; each subject then received 1 weekly maintenance injection before posttreatment measurements were made. The response to immunotherapy was assessed before immunotherapy and after the first weekly maintenance injection. Studies included responses to titrated skin prick tests to cat extract and an unrelated allergen and serum allergen-specific IgE and IgG4. Titrated nasal challenges were performed with cat extract; measurement of mRNA and secreted cytokines (IL-4, IL-5, and IFN-gamma) was done at 6 hours. Serum cytokines (IL-4, IL-5, IFN-gamma) were measured, and flow cytometric analysis of intracellular cytokines (IL-4, IL-5, IFN-gamma) was performed. Cat allergen-stimulated lymphocyte proliferation was performed with measurement of cytokines in the supernatant (IL-4, IL-5, IFN-gamma). RESULTS: All 28 subjects completed the study. Significant and dose-dependent differences were encountered in the titrated skin prick tests (P =.008), the cat-specific IgG(4) (P =.01), and the reduction in CD4+/IL-4+ PBMCs on flow cytometry (P =.03). There were no significant differences between placebo and cat dander extract containing Fel d 1 0.6 microg. Both extracts containing 3.0 microg and 15.0 microg produced significant decreases in skin prick test sensitivity (P =.02 and P =.002, respectively). The extracts containing 3.0 microg and 15.0 microg produced significant increases in cat-specific IgG4 (P =.01 and P =.006, respectively). Only the 15.0-microg-per-dose extract produced a significant reduction in the percent of CD4+/IL-4+ PBMCs (P =.003). CONCLUSION: In this double-blind, placebo-controlled study, a maintenance dose of cat dander extract containing 15.0 microg Fel d 1 produced the most consistent immunologic response. A dose of 3.0 microg reduced skin prick test sensitivity and increased cat-specific IgG4 but did not reduce the circulating CD4+/IL-4+ PBMCs, a change that is likely related to the clinically significant response to allergen immunotherapy. These findings suggest that a maintenance dose of 15.0 microg of Fel d 1 is most apt to be clinically effective for allergen immunotherapy.     

Immunotherapy with an alum-adsorbed Parietaria-pollen allergoid: a 2-year, double-blind, placebo-controlled study

A double-blind, placeo-controlled study was performed in order to confirm the safety, suitability, and efficacy of an alum-adsorbed Parietaria judaica -pollen allergoid, Allergovit®, for allergen-specific immunotherapy. Parietaria pollen is an important cause of pollinosis, particularly in the Mediterranean zone, where it may be encountered for up to 8–9 months of the year. It is an aggressive allergen, and the doses tolerated during immunotherapy are less than those achieved with grass pollen. This factor increases the desirability of using therapeutic preparations with minimal IgE-binding activity, such as allergoids, in order to reduce the risk of side-effects and enable patients to tolerate a higher dose of allergen, thereby increasing the chances of successful specific immunotherapy. Forty patients with rhinitis and/or asthma were allocated at random to active- or placebo-treatment groups at the beginning of the study. All patients received the active preparation during the second year of the study. Immunotherapy was well tolerated by all patients and the incidence of side-effects was low. Treatment resulted in significant reductions in specific cutaneous reactivity and increases in nasal tolerance. A progressive improvement in nasal inspiratory peak flow in association with the immunotherapy indicated a reduction in nasal inflammation. These objective assessments of efficacy endorsed the results from the patients' diary cards, which indicated significant improvements in symptoms and reductions in the use of medication. The immunologic activity of the therapeutic preparation was demonstrated by the induction of a significant specific-IgG antibody response, with increases in IgG4 during the second year of treatment. We conclude that the safety and efficacy of immunotherapy with the Parietaria allergoid make it suitable for consideration in the treatment of patients with Parietaria -pollen-induced rhinitis or asthma.     

Immunotherapy with Alpare® in patients with respiratory allergy to Parietaria pollen: a two year double-blind placebo-controlled study

Allergy to Parietaria judaica pollen causes significant morbidity in many areas of the world. In addition to rhinitis, patients who are allergic to this pollen have a high incidence of asthma. The pollinating season is long, making this particular allergy challenging for clinicians to treat. This study was designed to determine if immunotherapy with an alum adsorbed partially purified Parietaria extract (Alpare Parietaria) containing a targeted maintenance dose of 12 500 BUs was effective in decreasing rhinitis symptoms in patients allergic to Parieiaria. Using a double-blind placebo-controlled technique 36 patients received placebo or active extract for 2 years. Twenty (11 placebo and nine active) completed the 2 year study. Efficacy of treatment was evaluated by determining changes in skin reactivity, visual analog scores, diary symptom scores and end of study assessments. Reactions were monitored as well. Skin-test suppression was marginally significant in the actively treated group after 1 year and showed even more significant suppression after the second year. Nasal block, rhinorrhoea and sneezing all were significantly decreased in the active group. The nasal provocation test did not show a significant change after 1 year, in either group, but after 2 years of treatment the active group did show significant improvement. Although almost all patients in the actively treated group experienced local reactions, the incidence of systemic reactions was not different between the two groups. In conclusion, immunotherapy with this extract at this dose was effective in ameliorated rhinitis symptoms in patients allergic to Parietaria judaica.     

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.     

A double-blind, placebo-controlled study of immunotherapy with an alginate-conjugated extract of Parietaria Judaica in patients with Parietaria hay fever

A double-blind, placebo-controlled study was conducted to evaluate the efficacy and safety of immunotherapy (IT) with a partially purified alginate-conjugated extract of Parietaria judaica (Conjuvac® Parietaria , Dome/Hollister-Stier) in patients suffering from rhinoconjunctivitis caused by Parietaria pollen. Eighteen patients (10 women, 8 men, mean age 35 years) received active treatment and 17 (10 women, 7 men, mean age 42.5 years) received placebo. Actively treated patients had significantly lower nasal symptom/medication scores (running nose P = 0.0087 and sneezing P = 0.048) during the Parietaria pollen season. Significant decreases in specific skin ( P > 0.01), nasal ( P > 0.05), and conjunctival ( P > 0.01) reactivity to the Parietaria extract and significant increases of specific IgG ( P > 0.001), IgGI ( P > 0.001), and IgG4 ( P > 0.001) in actively treated patients, but not in placebo, were found. IT was well tolerated, the active extract inducing five mild systemic reactions (four rhinitis and one urticaria) and placebo two (rhinitis). A significant correlation was found between low skin reactivity and high specific IgG ( P = 0.0002) and IgG4 ( P = 0.036). These findings indicate that IT with a partially purified P. judaica extract is an effective and safe treatment for Parietaria pollen allergy. The correlation between low immediate skin reactivity and high specific IgG and IgG4 suggests that, at least in the studied cutaneous model, these antibodies may exert a blocking effect.     

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.     

Effect of azelastine on the seasonal increase in non-specific bronchial responsiveness to methacholine in pollen allergic patients. A randomized, double-blind placebo-controlled, crossover study

Azelastine, a phthalazinone derivative, is a new potent, long acting, orally active anti-allergic compound with particularly strong H1-histamine receptor antagonistic effects which has been proven to possess in vitro and in vivo a number of anti-inflammatory properties. The aim of the present study was to investigate whether azelastine would be able to prevent and/or reverse the seasonal increase in non-specific bronchial responsiveness to methacholine in pollen allergic patients. Twelve atopic patients (5 males, mean age 31 years), skin positive exclusively to grass and/or Parietaria pollen extract, with rhinitis and mild asthma occurring in the spring for at least two years previously, were studied. After a 2 week run-in period, oral azelastine, 4 mg twice daily, or placebo, was given for 2 weeks from the start of the pollen season, according to a randomized, double-blind design. After 2 weeks, the treatments were crossed over. During both the run-in and study periods, patients recorded rhinitis and asthma symptoms, additional antihistamine and bronchodilator drugs taken and peak expiratory flow measurements. A methacholine inhalation test was carried out on four occasions in each patient: before the run-in period, before the start of the treatment, and at the end of the two 2 week treatment periods. Azelastine significantly reduced rhinitis symptoms and the need for antihistamine drugs, whereas asthmatic symptoms, use of bronchodilator drugs, peak flow recordings and bronchial responsiveness to methacholine were unaffected by the treatment. Compliance level and adverse side-effects were not significantly different between active treatment and placebo. In the final subjective evaluation of the two treatments, eight out of 12 patients preferred azelastine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo-controlled study

BACKGROUND: The allergological relevance of Ambrosia in Europe is growing but the efficacy of the injective immunotherapy for this allergen has been documented only in Northern America. OBJECTIVE: We sought to study the safety and efficacy of injective immunotherapy in European patients sensitized to Ambrosia artemisiifolia. METHODS: Thirty-two patients (18 M/14 F, mean age 36.78, range 23-60 years) suffering from rhinoconjunctivitis and/or asthma and sensitized to Ambrosia were enrolled and randomized in a double-blind, placebo-controlled (DBPC) study lasting 1 year. A maintenance dose corresponding to 7.2 microg of Amb a 1 was administered at 4-week intervals after the build-up. During the second and the third year, all patients were under active therapy in an open fashion. Symptom and medication scores, skin reactivity to Ambrosia (parallel line biological assay), and pollen counts were assessed throughout the trial. RESULTS: Twenty-three patients completed the trial. No severe adverse event was observed. During the DBPC phase, actively treated patients showed an improvement in asthmatic symptoms (P=0.02) and drug (P=0.0068) scores days with asthmatic symptoms (P=0.003), days with rhinitis symptoms (P=0.05), and days with intake of drugs (P=0.0058), as compared to before therapy. No improvement for any of these parameters was detected in the placebo group. Moreover, the number of days with rhinitis and asthma was significantly higher in the placebo as compared to the active group (P=0.048 and P<0.0001, respectively). Patients who switched from placebo to active therapy improved in rhinoconjunctivitis, asthma, and drug intake. The skin reactivity decreased significantly (12.2-fold, P=0.0001) in the active group whereas a slight increase (1.07-fold, P=0.87) was observed in the placebo group after the DBPC phase. After switching to active therapy, patients previously under placebo showed a significant decrease of this parameter (4.78-fold, P=0.002). CONCLUSION: Injective immunotherapy is safe and clinically effective in European patients sensitized to Ambrosia.     

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.     

Specific immunotherapy with a standardized latex extract in allergic workers: a double-blind,placebo-controlled study

BACKGROUND: Preventive measures have been proposed to reduce the risk of sensitization to natural rubber latex (NRL), but this is not always feasible. OBJECTIVE: The aim of this study was to determine the efficacy and safety of specific immunotherapy with a standardized latex extract in sensitized workers. METHODS: Twenty-four patients allergic to NRL with contact urticaria (n = 8) and rhinitis or asthma (n = 16) were included (16 in the active group and 8 in the placebo group). Treatment started in a cluster immunotherapy protocol, with injections every week for 3 months and then every other week for another 3 months. RESULTS: Patients in the active group had significantly lower values than patients in the placebo group in skin terms of reactivity to NRL (P <.01), rubbing test results (P =.047), and latex glove use test results (P =.046) after 6 months of treatment. There were no significant differences between the active and placebo groups in symptom scores, use of medication, self-assessment, or methacholine test results either before or after treatment. Differences in nasal and bronchial symptoms during specific inhalation challenges (P = not significant and P =.05, respectively) were observed in favor of the active group. In the active group 32 systemic reactions were observed (8% of doses), mostly during the build-up period, being more frequent in patients with respiratory symptoms (P =.004). All reactions responded promptly to treatment. CONCLUSION: Clinical efficacy was shown mainly on cutaneous symptoms, although an improvement in rhinitis and asthma symptoms was also observed during specific inhalation challenges. Latex-specific immunotherapy might be a useful approach for the treatment of latex allergy in sensitized workers.     

A double-blind, placebo-controlled trial of local nasal immunotherapy in allergic rhinitis to Parietaria pollen

We assessed the efficacy and safety of local nasal immunotherapy (LNIT) using an extract in macronized powder form of Parietaria pollen, a very important allergenic plant in the Mediterranean and other parts of the world. Twenty-six patients aged 13–37 years, with seasonal allergic rhinitis to this pollen, were enrolled in a double-blind placebo-controlled trial, carried out from autumn 1991 to the end of June 1992. They were selected on the basis of a positive skin-prick test, radioallergosorbent test (RAST) and intranasal challenge to Parietaria antigen. Patients were randomly divided into two groups of 13; the first group was given Parietaria antigen, and the second placebo. We recorded mean weekly symptom scores and drug consumption for 17 weeks during the pollen season in the year 1992, and specific serum-IgE and IgG levels. Three patients in the active group withdrew from the study because of bronchial symptoms. A significant difference was observed in mean weekly nasal symptom scores, in drug consumption and in specific nasal threshold to Parietaria allergenic extract in the treated and control groups. No difference was observed in serum IgE and IgG levels. Serum IgE levels rose significantly only in the control group after the pollen season. This study indicates that LNIT may be a useful alternative to traditional subcutaneous immunotherapy in patients with allergic rhinitis.