Average Adjusted Symptom Score Research Articles

Long-term benefit after allergen immunotherapy to HDM in elderly patients with allergic rhinitis.

Allergen immunotherapy (AIT) is an effective therapy for allergic rhinitis and may have long-term benefits. However, these benefits have not been strictly defined for older people. The evaluation of the effectiveness of AIT in patients over 60 with allergic rhinitis and house dust mites (HDM) allergy over a period of 7 years was performed. Patients after three years of HDM-AIT were observed to assess the sustained clinical effect of treatment. The average adjusted symptom score (AAdSS) and sIgG4 were monitored for 7 years after sublingual (SLIT) and injection AIT (SCIT). After 3 years of HDM-AIT, a significant clinical effect was observed in the group after SLIT and SCIT based on AAdSS compared to the baseline and the placebo group (p < 0.05). After 7 years of follow-up, there was a sustained trend of decrease in clinical symptoms in desensitized patients relative to placebo. Serum sIgG4 was constantly present in all desensitized patients. AIT may be beneficial for treating seniors with allergic rhinitis and allergies to house dust mites.

Predictive methods for efficacy of house dust mite subcutaneous immunotherapy in allergic rhinitis patients: a prospective study in a Chinese population.

Allergen-specific immunotherapy (AIT) is the only available treatment that can induce specific immune tolerance to allergens. However, the treatment course lasts >3 years, and there is no reliable method to predict treatment response. Therefore, in this study we aimed to establish a method that can predict treatment response to AIT in the second year. This prospective study enrolled 119 patients who had undergone 2-years of standard-quality house dust mite subcutaneous immunotherapy. Clinical characteristics, skin-prick test response, and treatment response were evaluated at months 4, 6, 12, and 18. Effective AIT was defined as a 25% reduction in average adjusted symptom score (AAdSS) from baseline at the end of the second year of immunotherapy. The overall efficacy rate at the end of year 2 of the AIT was 67.4%. Age, sex, asthma, body mass index, smoking history, and aeroallergen categories were not associated with efficacy of AIT. Meanwhile, efficacy data at month 4 (odds ratio [OR], 4.250; p = 0.004), month 6 (OR, 10.476; p < 0.000), month 12 (OR, 18.000; p < 0.000), and month 18 (OR, 9.716; p < 0.000) were associated with month 24 efficacy. The area under the curve for improvement at 4, 6, 12, and 18 months was 0.805, 0.834, 0.837, and 0.854, respectively. Efficacy of AIT at months 4, 6, 12, and 18 is strongly associated with efficacy at month 24. Efficacy as early as month 4 can predict efficacy at the second year, and this may help to determine the need for long-term treatment. Our findings may be useful for identifying novel treatment strategies for AIT.

Efficacy of House Dust Mite Sublingual Tablet in the Treatment of Allergic Rhinoconjunctivitis: A Randomized Trial in a Pediatric Population

To investigate the efficacy, safety, and immunologic response of standardized sublingual house dust mite (HDM) tablets in Japanese pediatric patients.Included in the study were patients ≥5 and ≤16 years of age with allergic rhinitis symptoms for ≥2 years, a score of ≥3 on quantitative analysis of specific immunoglobulin E antibody to Dermatophagoides pteronyssinus and/or Dermatophagoides farinae antigens, positive nasal provocation test result for HDM, and Rhinitis Total Symptom Score ≥6 points per day for 7 days before randomization. Those with symptoms from other allergens, mild persistent or more-severe asthma, or inhaled corticosteroid use were excluded.This multicenter, double-blind, randomized placebo-controlled trial was conducted at 51 Japanese medical institutions from October 2015 to December 2016. Subjects were randomly assigned 1:1 to placebo or HDM tablets with an index of reactivity of 300 daily for 52 weeks. Symptoms and rescue medication use were recorded daily in a patient diary. The primary end point was the average adjusted symptom score for week 48 to 52, derived from daily Rhinitis Total Symptom Scores and adjusted for rescue medication use.Of 438 patients who were randomly assigned, 193 patients in the treatment group and 210 patients in the placebo group completed the study. The average adjusted symptom score was significantly lower in the treatment group compared with placebo (6.32 vs 7.27, P = .0005), with a least-squares mean difference of −13.1%. Improvement was seen at weeks 8 to 10 and was maintained throughout. Nasal Individual Symptom Scores were significantly lower in the treatment group, whereas Average Rescue Medication Scores and Ocular Individual Symptom Scores were not. Specific immunoglobulin E antibodies to HDM nearly doubled, whereas specific immunoglobulin G4 antibodies approximately tripled in the treatment group. Mild or moderate adverse events (oral pruritus, mouth edema, throat irritation, ear pruritus, and mouth swelling) occurred in most patients (96.8% of treated patients, 94.5% of placebo patients), typically from days 1 to 14. Two serious adverse events were reported in the placebo group and 6 were reported in the treatment group, leading to drug discontinuation in 1 patient with pseudocroup. Overall, 8% of randomly assigned patients discontinued the study, mostly because of adverse effects. There were no deaths or anaphylactic events requiring intramuscular epinephrine.This study demonstrates efficacy and safety of HDM sublingual tablets in pediatric patients with perennial allergic rhinitis due to HDM allergy. Treatment conferred significant and sustained improvement in symptom scores, with a similar immunologic response and safety profile, as previously shown in older age groups.This study is limited by a lack of objective outcomes, such as peak nasal inspiratory flow or nasal provocation tests. The investigators also excluded patients with persistent asthma and symptomatic rhinitis due to other allergens, which commonly occur in patients with HDM-triggered rhinitis. Although modest improvement in symptoms was shown, daily therapy over a 52-week treatment course may be impractical for pediatric patients. One likely goal of HDM immunotherapy may be to decrease use of other medications, but this was not seen in the current study. Further studies are needed in this population to assess optimal treatment duration and whether treatment confers sustained benefit after drug discontinuation.

Efficacy of house dust mite sublingual tablet in the treatment of allergic rhinoconjunctivitis: A randomized trial in a pediatric population.

BackgroundThe efficacy and safety of 300 index of reactivity (IR) tablets of house dust mite (HDM) allergen extracts in Japanese pediatric (5‐16 years old) patients with allergic rhinitis (AR) were assessed in a double‐blind, randomized, placebo‐controlled study (JAPIC CTI‐152981).MethodsPatients were randomized 1:1 to HDM sublingual tablets or placebo once daily for 52 weeks. The primary end‐point was average adjusted symptom score (AASS; average of daily Rhinitis Total Symptom Scores, comprising sneezing, rhinorrhea, nasal congestion, and nasal pruritus, adjusted for rescue medication use), analyzed during Weeks 48‐52 (mixed‐effects model for repeated measures).ResultsOf 438 patients randomized, 403 (92%; 193 active, 210 placebo) completed the study. AASS (least‐squares [LS] mean [SE]) during Weeks 48‐52 was significantly (P = 0.0005) lower in the active group compared with placebo (6.32 [0.20] vs 7.27 [0.19]; relative LS mean difference, −13%). Immunological responses (IgE and IgG4 antibodies specific to antigens of two HDM species) were significantly greater in the active group compared with placebo (P < 0.0001). Almost all patients experienced mild or moderate adverse events (AEs). The most common treatment‐related AEs were oral pruritus, mouth edema, throat irritation, and ear pruritus. One patient experienced serious pseudocroup (subglottic laryngitis) that recovered. There were no deaths or anaphylaxis requiring the use of injectable adrenaline.ConclusionsThe HDM tablet significantly improved symptoms of HDM‐induced perennial AR and was associated with a significant immunological response. The safety profile in pediatric patients was consistent with that in adults, with no new safety concerns.

Prolonged effect of allergen sublingual immunotherapy to grass pollen

ABSTRACTBackground: The prolonged effect of allergen immunotherapy is unknown, especially in older patients. Objective: The three-year effect of sublingual allergen-specific immunotherapy (AIT) to grass pollen on elderly patients with allergic rhinitis was analyzed.Methods: Thirty-eight elderly patients (63.18 ± 3.12 yrs.) underwent AIT to grass pollen, were monitored for three years and were compared to a placebo group. AIT was performed with the use of an oral Staloral 300 SR grass extract (Stallergens Greer, London, UK) or a placebo. Symptoms and medication scores, represented by the average adjusted symptom score (AAdSS), the serum level of IgG4 to Phl p5 and the quality of life were assessed immediately after AIT and three years later. Results: After AIT, the AAdSS was significantly decreased and remained lower than in the placebo group during the three years after AIT. Serum-specific IgG4 against Phl p5 increased during the AIT trial in the study group. For the three years of observation after AIT, there were no significant changes in specific IgG4 levels against the analyzed allergens in comparison to the results immediately after AIT. The quality of life, based on the Rhinoconjunctivitis Quality of Life Questionnaire, was significantly decreased in patients who received AIT, from 1.83 (95%CI: 1.45–1.96) to 0.74 (95%CI: 0.39–1.92) (p < 0.05) to 0.82 (95%CI: 0.45– 1.04) three years after AIT.Conclusion: A prolonged positive effect after AIT to grass pollen was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect.

Evidence of the efficacy and safety of house dust mite subcutaneous immunotherapy in elderly allergic rhinitis patients: a randomized, double-blind placebo-controlled trial

BackgroundAllergen specific immunotherapy (AIT) in elderly patients is controversial, and there is still little evidence supporting the safety and efficacy of this treatment in this population. The study objective was to evaluate the safety and efficacy of AIT for house dust mite allergens in patients over 65 years of age with allergic rhinitis (AR) and a documented allergy to house dust mites. The primary endpoint was the change from baseline in the mean average adjusted symptom score (AAdSS) and the total combined rhinitis score (TCRS) difference in the least square means for the label compared to placebo.MethodsFifty-eight AR elderly patients who were monosensitized to house dust mites were individually randomized in comparable numbers to one of two parallel groups with the following interventions: 2 years of perennial AIT using PURETHAL Mites or placebo. The symptoms and medication scores were presented as the AAdSS and TCRS. Quality of life, based on the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal allergen provocation responsiveness, serum allergen-specific IgG4 to D. pteronyssinus and D. farinae and Der p1 and Der p2 were monitored. The intent-to-treat population was analysed.ResultsAfter 24 months of AIT, AAdSS significantly decreased from 4.27 ± 1.58 to 1.82 ± 0.71 (p < 0.05). The TCRS was significantly decreased after 2 years of AIT. Serum-specific IgG4 against D. pteronyssinus, D. farinae, Der p1, and Der p2 increased during the AIT trial in the study group. The RQLQ score was significantly improved in patients who received AIT, from 1.86 (95% CI 1.51–1.78) to 1.26 (95% CI 1.09–1.55). Two mild systemic anaphylactic reactions (degree I) were reported after injections in the active group during the AIT therapy.ConclusionThe DBPC trial showed AIT for house dust mite allergens was effective and safe in elderly patients with allergic rhinitis.Trial registrationThis randomized, double-blinded placebo-controlled (DBPC) trial was conducted at one centre (ClinicalTrials.gov no. NCT03209245)

Prolonged effect of allergen sublingual immunotherapy for house dust mites in elderly patients

BackgroundThe prolonged effect of allergen immunotherapy is unknown, especially in older patients. ObjectiveTo analyze the 3-year effect of sublingual allergen-specific immunotherapy (SLIT) to house dust mites in elderly patients with allergic rhinitis. MethodsForty-seven elderly patients (65.78 ± 4.89 years old) underwent SLIT to house dust mites and were monitored for 3 years and compared with a placebo group. SLIT was performed with the use of oral Staloral 300 SR Der p and Der f 50/50% extract (Stallergens Greer, London, United Kingdom) or placebo. Symptoms and medication score, represented by the average adjusted symptom score (AAdSS), serum level of immunoglobulin (Ig) G4 to Dermatophagoides pteronyssinus, Dermatophagoides farinae, Der p 1, and Der p 2, and quality of life, were assessed immediately after SLIT and 3 years later. ResultsThe AAdSS was significantly decreased after SLIT, and the level remained low during the 3 years after SLIT compared with placebo. Serum-specific IgG4 against D pteronyssinus, D farinae, Der p 1, and Der p 2 increased during the SLIT trial in the study group. For the 3 years of observation after SLIT, there were no significant changes of specific IgG4 levels against the analyzed allergens compared with results just after SLIT. Quality of life based on the Rhinoconjunctivitis Quality of Life Questionnaire score was significantly decreased in patients who received SLIT, from 1.48 (95% confidence interval 1.33–1.79) to 0.98 (95% confidence interval 0.67–1.07; P < .05) compared with 0.94 (95% confidence interval 0.55–1.04) 3 years after SLIT. ConclusionThe prolonged positive effect after SLIT to house dust mites was observed in elderly patients with allergic rhinitis. Further trials are needed to confirm this effect. Trial RegistrationClinicalTrials.gov Identifier: NCT01605760

ASCIA‐P52: TREATMENT WITH HOUSE DUST MITE TABLETS FOR SUBLINGUAL IMMUNOTHERAPY: RELATIONSHIP BETWEEN ALLERGIC DISEASE SEVERITY AND EFFICACY IN A CONFIRMATORY STUDY

House dust mite (HDM) sublingual immunotherapy tablets administered daily in allergic rhinitis patients has been evaluated after a 12-month treatment period in a randomized, double-blind, study in 509 adults in Europe. The post-treatment effect was subsequently assessed over a 12-month period. 300IR and 500IR doses of HDM or placebo tablets were administered to adults with HDM-associated allergic rhinitis in a randomized DBPC study. After the treatment phase, subjects were monitored during a 12-month treatment-free period. Analyses were performed to evaluate the relationship between disease severity and efficacy. Centers pooled by geographical zones were ranked according to the mean average Adjusted Symptom Score (AASS, that adjusts symptom severity with rescue medication use) in the placebo group. Pooled centers were then grouped into statistical tertiles, each having about one-third of all subjects. In the 300IR group (n = 153), subjects experienced symptom improvement compared to the placebo group (n = 163). During the treatment period, the overall treatment effect estimated as the difference in AASS LS means was at 0.69, (CI95% [−1.25, 0.14], p = 0.0150), i.e., a relative difference of −17.9% from placebo. For the low-, medium- and high-severity tertiles (n = 98, 94 and 102), the relative differences in this score for subjects receiving 300IR vs. placebo were +10.3%, −7.2% and −39.3 %, respectively. During the treatment-free year, the relative differences in this score for the subjects receiving 300IR vs. placebo were −5.6%, −4.8% and −29.9% for the low-, medium- and high-severity tertiles (n = 74, 108 and 87), respectively. These results showed that the more severe the disease, the greater the treatment effect. The 300IR dose has demonstrated efficacy during treatment and over the year post-treatment. The overall treatment effect observed was driven by efficacy in the tertile of pooled centers in which subjects in the placebo group exhibited the highest level of symptoms, with about 39% improvement versus placebo.

O17 ‐ Assessment of efficacy and safety of sublingual tablets of house dust mite allergen extract in children and adolescents with allergic rhinitis

Methods Participants aged 5 to 17 years of age, with at least a 1year history of HDM-associated AR requiring regular intake of symptomatic treatment, a positive skin prick test to HDM, HDM-specific serum IgE ≥0.7 kU/L, and an Average Rhinitis Total Symptom Score (ARTSS, scale: 0-12) ≥5 during a 7-day screening period were randomized (1:1) to receive 300IR or placebo tablets once daily for a year. Participants recorded their rhinitis symptoms and use of rescue medication. The primary efficacy endpoint, Average Adjusted Symptom Score (AAdSS), which adjusts symptom score for rescue medication use, was assessed over the last 2 months of the treatment period and analyzed by ANCOVA.

Sustained efficacy and safety of a 300IR daily dose of a sublingual solution of birch pollen allergen extract in adults with allergic rhinoconjunctivitis: results of a double‐blind, placebo‐controlled study

BackgroundAllergic rhinoconjunctivitis (ARC) due to birch pollen is a growing health concern in Europe. Here, we report the efficacy and safety of 300IR birch pollen sublingual solution administered discontinuously for 2 consecutive years to patients with birch-associated allergic rhinoconjunctivitis.MethodsBirch pollen-allergic adults were randomized in this double blind study to 300IR birch pollen sublingual solution or placebo, daily, starting 4 months before and continuing through the pollen season for two pollen seasons. Randomization was stratified according to the presence or absence of oral allergy syndrome (OAS). The primary efficacy endpoint was the Average Adjusted Symptom Score (AAdSS) over the second pollen season and was analyzed by ANCOVA. Secondary efficacy endpoints included the AAdSS over the first pollen period. Safety was evaluated by means of adverse event monitoring.Results574 patients (284 in the active group and 290 in the placebo group) were randomized and 496 completed the study. Over the second pollen period, the least square (LS) mean AAdSS was significantly lower in the 300IR group than in the placebo group (LS mean difference −2.04, 95% CI [−2.69, −1.40], (p <0.0001) with a relative reduction of 30.6%. Results were consistent in patients with and without OAS (−33.6% and −28.4%, respectively). A significant reduction in LS mean AAdSS was also observed over the first pollen season. The most frequently reported adverse events were application site reactions: oral pruritus, throat irritation, and mouth edema. There were no reports of anaphylaxis.ConclusionsPre- and co-seasonal treatment with 300IR birch pollen sublingual solution demonstrated sustained clinical efficacy over 2 pollen seasons and was well tolerated in adults with birch pollen-associated allergic rhinoconjunctivitis. Efficacy results were consistent in patients with and without oral allergy syndrome.Trial registrationClinicalTrials.gov: NCT01731249.

Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis

Preliminary studies have suggested the efficacy of sublingual tablets of house dust mite (HDM) extracts in adults with allergic rhinitis. We sought to assess the efficacy and safety of 2 doses of HDM sublingual tablets over 1 treatment year and the subsequent immunotherapy-free year. Adults with HDM-associated allergic rhinitis were randomized in a double-blind, placebo-controlled study to receive 500 index of reactivity (IR) tablets, 300IR tablets, or placebo administered once daily for 1 year and were followed for the subsequent year. The primary efficacy variable was the Average Adjusted Symptom Score over the year 1 primary period (ie, October 1 to December 31). Symptoms and rescue medication scores, onset of action, patient-reported outcomes, and safety were secondary variables. The same end points were evaluated during the immunotherapy-free year. The primary efficacy end point was analyzed by using analysis of covariance. Five hundred nine participants were randomized, and 427 continued in the immunotherapy-free year. Both the 500IR and 300IR HDM sublingual tablets significantly reduced mean Average Adjusted Symptom Scores compared with placebo by -20.2% (P = .0066) and -17.9% (P = .0150), respectively. Efficacy of both doses was maintained during the treatment-free follow-up phase. The onset of action was at 4 months. Participants' global evaluation of treatment success was significantly higher in the 500IR and 300IR groups compared with the placebo group (P = .0206 and P = .0001, respectively). Adverse events were generally application-site reactions. There were no reports of anaphylaxis. Twelve months of treatment with 500IR and 300IR sublingual tablets of HDM allergen extracts was efficacious and well tolerated. Efficacy was maintained during the treatment-free follow-up year.

Post‐treatment efficacy of discontinuous treatment with 300IR 5‐grass pollen sublingual tablet in adults with grass pollen‐induced allergic rhinoconjunctivitis

Sustained efficacy over three pollen seasons of pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet has been demonstrated in adults with moderate-severe grass pollen-associated allergic rhinoconjunctivitis. To assess the efficacy of discontinuous treatment with 300IR 5-grass pollen sublingual tablet during the post-treatment pollen season of this long-term study. Adults aged 18-50, sensitized to grass pollen, with a history of allergic rhinoconjunctivitis for more than two pollen seasons, and a retrospective rhinoconjunctivitis total symptom score ≥ 12 (0-18 scale), were randomized to receive Placebo or a 300IR tablet daily beginning either 4 months (4M) or 2 months (2M) prior to each pollen season and continuing for its duration for three consecutive years. They were followed over the subsequent immunotherapy-free pollen season. Post-treatment efficacy was evaluated using the Average Adjusted Symptom Score (AAdSS, adjusting the Rhinoconjunctivitis Total Symptom Score for rescue medication usage) during the post-treatment pollen period. Secondary endpoints included Average Rhinoconjunctivitis Total Symptom Score (ARTSS), Average Rescue Medication Score (ARMS), overall Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score and safety evaluation. Efficacy variables were analysed using ancova. Overall, 435 patients contributed to the Year 4 efficacy analyses. The Least-Squares (LS) mean differences (95% confidence interval) in AAdSS between active treatment and Placebo over the fourth pollen period were -1.14 (-2.03; -0.26) (P = 0.0114) and -1.43 (-2.32; -0.53) (P = 0.0019) in the (4M) and (2M) groups, corresponding to -22.9% and -28.5% relative LS mean differences (vs. Placebo) respectively. The active groups also showed statistically significant differences compared to Placebo in ARTSS, ARMS and overall RQLQ score. No safety risk was identified during the post-treatment period. Pre- and co-seasonal treatment with 300IR 5-grass pollen sublingual tablet administered discontinuously for three consecutive years is efficacious post-treatment, safe and well tolerated. Benefits of treatment were meaningful to patients.

Economic Evaluation of 5-Grass Pollen Tablets Versus Placebo in the Treatment of Allergic Rhinitis in Adults

BackgroundAllergen immunotherapy (AIT) is aimed at modifying the immune response to a causative allergen, thereby reducing clinical symptoms and symptomatic medication intake and improving quality of life. Long-term AIT research has led to the development of 5-grass pollen tablets, currently indicated for the treatment of grass pollen-induced allergic rhinitis (AR).MethodsA post-hoc analysis was conducted using the Average Adjusted Symptom Score (AAdSS) to compare the effect of treatment of AR with 5-grass pollen tablets versus placebo treatment. Using the results of the VO34.04 and VO53.06 trials and economic data, cost-effectiveness analysis of 5-grass pollen tablet treatment was performed from the Italian third-party payer perspective with cost data derived from a study of 2008 updated to 2011. Also a societal perspective was considered by using the costs related to the losses of productivity by following the human capital approach. Using the results of the analysis, the estimated receiver-operating characteristic curve was plotted to evaluate medication effectiveness in terms of quality-adjusted life years (QALYs) and a decision tree constructed to model the possible outcomes and costs for adults and paediatric patients with a low, medium, and high AAdSS. Finally, probabilistic sensitivity analysis was conducted to test the robustness of the results as well as their consistency at an assumed cost-effectiveness threshold of € 30,000/QALY.ResultsThe results indicate that compared to the placebo, the 5-grass pollen tablet treatment provides a benefit of 0.127 QALYs in medium AAdSS patients and of 0.143 QALYs in high AAdSS patients. The 5-grass pollen tablet treatment was found to cost € 1,024/QALY for patients with a medium AAdSS and € 1,035/QALY for patients with a high AAdSS. Of all the simulations performed in the probabilistic sensitivity analysis, 99 % indicated that the incremental cost-effectiveness ratio of the 5-grass pollen tablet treatment was below the threshold of € 30,000/QALY in patients with medium and high AAdSS, whereas it was found to be dominated in 67 % of simulations related to patients with low AAdSS.ConclusionThe 5-grass pollen tablet is a cost-effective treatment for adult AR patients with a medium or high AAdSS. This finding should be carefully considered when deciding the management strategy for these patients.

Absence of IgE neosensitization in house dust mite allergic patients following sublingual immunotherapy

The impact of sublingual immunotherapy (SLIT) on IgE neosensitization remains to be evaluated in large cohorts of patients. The aim of this study was to assess the dynamics of antibody responses induced in patients with allergic rhinitis during a 12-month treatment with sublingual tablets of house dust mites (HDM) allergen extracts. Antibody responses were assessed in relationship with neosensitization and clinical benefit in sera from 509 European house dust mite-allergic patients before and after 1year of daily sublingual immunotherapy, using tablets containing Dermatophagoides pteronyssinus plus D farinae extracts or placebo (ClinicalTrials.gov NCT00674700). Patients were followed for one additional year after treatment cessation. IgE and IgG4 antibodies specific for mite extracts or purified group 1, 2 and 10 allergens were assessed using Immulite, Immunocap and ISAC assays. After 1year of SLIT, mite-specific IgE and IgG4 titres increased by 1.5-fold and fourfold, respectively, in the active, but not in the placebo group. A strong IgG4 induction occurred in a subgroup (i.e. 10-15%) of "immunoreactive" patients, without any correlation with improvement in the average adjusted symptom score. Pre-existing IgE levels to purified mite allergens were not impacted during immunotherapy, and no de novo IgE responses to group 1, 2, 10 allergens were induced in patients who were unsensitized prior to immunotherapy. Similarly, no IgE neosensitization to wheat germ or yeast components used in the mite culture medium was observed. We document in a cohort of 509 patients followed over a 2-year period that SLIT does not induce any IgE neosensitization to allergens contained in the vaccine, such as groups 1, 2 as well as the food-related group 10 allergen. This observation further corroborates the safer safety profile of SLIT over SCIT.

Re: The average Adjusted Symptom Score, a new primary efficacy end‐point for specific allergen immunotherapy trials

Summary Background In clinical trials, the efficacy of immunotherapy for allergic rhinoconjunctivitis symptoms is often evaluated with the average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with a lower ARTSS vs. placebo but use of rescue medication to alleviate symptoms reduces the RTSS and decreases the mean difference between active treatment and placebo groups. Objective To develop and describe the average Adjusted Symptom Score (AdSS), a new end-point reflecting symptom severity and rescue medication use in allergic rhinoconjunctivitis trials. Methods To calculate the AdSS, the RTSS is adjusted as follows: if a patient takes rescue medication on day d, the day's AdSS (AdSSd) is defined as the value of RTSSd or AdSSd−1, whichever is higher. The AdSS on the following day (AdSSd+1) is defined as the value of RTSSd+1 or AdSSd, whichever is higher. The average of the daily AdSSs (during the season) was calculated post hoc for two trials investigating the efficacy of five-grass pollen sublingual immunotherapy tablets in adult and paediatric patients and compared with the ARTSS and three other outcome measures (the average Rescue Medication Score (ARMS), the ARTSS and the average Combined Score). Results The average AdSS clearly discriminated between active and placebo treatments and confirmed the original ARTSS results. Adjustment for rescue medication use decreased the observed placebo effect. Conclusion and Clinical Relevance The average AdSS can be a valuable alternative to the ARTSS as a primary efficacy end-point in grass pollen allergic rhinoconjunctivitis trials. By adjusting the RTSS for rescue medication use, the AdSS can estimate symptom severity and the treatment effect more accurately. The AdSS is now being tested prospectively in large clinical trials. Cite this as: J.-M. Grouin, E. Vicaut, S. Jean-Alphonse, P. Demoly, U. Wahn, A. Didier, O. de Beaumont, A. Montagut, M. Le Gall and P. Devillier, Clinical & Experimental Allergy, 2011 (41) 1282–1288.

The average Adjusted Symptom Score, a new primary efficacy end‐point for specific allergen immunotherapy trials

The average Adjusted Symptom Score, a new primary efficacy end‐point for specific allergen immunotherapy trials

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Sustained 3-year efficacy of pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen–induced rhinoconjunctivitis

Seasonal allergic rhinoconjunctivitis affects millions of persons. The efficacy of allergen sublingual immunotherapy (SLIT) was demonstrated in previous short-term studies. We sought to evaluate the sustained efficacy of 2 dosing regimens of a pre- and coseasonal treatment with 300 IR (index of reactivity) 5-grass-pollen SLIT tablets (Oralair) compared with placebo assessed by using the average adjusted symptom score (AAdSS) at season 3 in adults with grass pollen-induced rhinoconjunctivitis. Six hundred thirty-three patients were treated for either 2 or 4 months before and then during the grass pollen season with active or placebo treatment for 3 consecutive seasons. The primary outcome was the AAdSS, a symptom score adjusted for rescue medication use, after 3 consecutive treatment seasons. Secondary outcomes were symptoms and rescue medication score, quality-of-life, and safety assessments. The mean AAdSS was reduced by 36.0% and 34.5% at season 3 in the 2- and 4-month pre- and coseasonal active treatment groups, respectively, compared with that in the placebo group (P < .0001 for both). Reductions were observed in total symptom scores and ISSs and the medication score, with a marked improvement in quality of life for both active groups compared with the placebo group at season 3. Most treatment-emergent adverse events were local reactions expected with SLIT, decreasing in number and intensity in each treatment season. Sustained efficacy of 2- and 4-month pre- and coseasonal treatment with the 300 IR tablet over 3 pollen seasons was demonstrated, with reduction in symptoms and rescue medication use. The treatment was well tolerated. Adverse events decreased in number and intensity over the 3 seasons.

The average Adjusted Symptom Score, a new primary efficacy end‐point for specific allergen immunotherapy trials

In clinical trials, the efficacy of immunotherapy for allergic rhinoconjunctivitis symptoms is often evaluated with the average Rhinoconjunctivitis Total Symptom Score (ARTSS). Effective treatment is associated with a lower ARTSS vs. placebo but use of rescue medication to alleviate symptoms reduces the RTSS and decreases the mean difference between active treatment and placebo groups. To develop and describe the average Adjusted Symptom Score (AdSS), a new end-point reflecting symptom severity and rescue medication use in allergic rhinoconjunctivitis trials. To calculate the AdSS, the RTSS is adjusted as follows: if a patient takes rescue medication on day d, the day's AdSS (AdSS(d)) is defined as the value of RTSS(d) or AdSS(d-1), whichever is higher. The AdSS on the following day (AdSS(d+1)) is defined as the value of RTSS(d+1) or AdSS(d), whichever is higher. The average of the daily AdSSs (during the season) was calculated post hoc for two trials investigating the efficacy of five-grass pollen sublingual immunotherapy tablets in adult and paediatric patients and compared with the ARTSS and three other outcome measures (the average Rescue Medication Score (ARMS), the ARTSS and the average Combined Score). The average AdSS clearly discriminated between active and placebo treatments and confirmed the original ARTSS results. Adjustment for rescue medication use decreased the observed placebo effect. The average AdSS can be a valuable alternative to the ARTSS as a primary efficacy end-point in grass pollen allergic rhinoconjunctivitis trials. By adjusting the RTSS for rescue medication use, the AdSS can estimate symptom severity and the treatment effect more accurately. The AdSS is now being tested prospectively in large clinical trials.