Allergen Tablets Research Articles

Utility of silver birch and house dust mite extracts derived from licensed sublingual tablets for nasal allergen challenge.

Nasal allergen challenge (NAC) is used to investigate the effects of allergen exposure and assess treatment efficacy in allergic rhinitis (AR). This study aims to establish dose-responses to NAC using licensed silver birch (SB) pollen and house dust mite (HDM) sublingual tablets as sources of the allergen extracts in participants with AR. Sixteen volunteers with HDM-induced perennial AR and 15 volunteers with SB pollen-induced seasonal rhinitis underwent a graded up-dosing NAC with extracts derived from HDM allergen (Acarizax®) and SB (Itulazax®) tablets, respectively. Total nasal symptom score (TNSS, range 0-12) and peak nasal inspiratory flow (PNIF) were recorded before, at 10min and at the end of the NAC. The dose of each allergen that provoked a TNSS of at least 7 ("provoking dose 7") in most allergic participants was identified. NACs using the "provoking dose 7" were performed on 5 non-allergic individuals to test for irritant effects. The "provoking dose 7" of HDM extract was used in a subgroup of two SB allergic, non-HDM allergic, volunteers, and vice versa for SB extract, to test for allergen specificity of the responses. Most patients experienced a TNSS of at least 7/12 at a median concentration of 1500AU/mL for both SB pollen and HDM. The average decline in PNIF at this dose was 63.15% for SB and 63.99% for HDM. NACs using the 1500AU/mL concentrations were performed on 5 non-allergic individuals with no symptomatic or PNIF response. 1500AU/mL of HDM extract produced no symptoms in SB allergics nor 1500AU/mL SB extract in HDM allergics. For both SB and HDM extracts, the optimal allergen dose for NAC to cause a moderate-severity response ("provoking dose 7/12") was 1500AU/mL. Licensed sublingual allergen tablets provide a readily available and inexpensive source of SB and HDM extracts for use in future interventional studies in AR.

Comprendre les raisons pour lesquelles les médecins choisissent les APSI en France : résultats de l’étude épidémiologique nationale en vie réelle, multicentrique, observationnelle, transversale STRATEGO

Study objectiveTo clarify the circumstances and reasons for prescribing allergens prepared specifically for an individual [named-patient products (NPPs)] when initiating allergen immunotherapy (AIT) in real-world conditions in mainland France. Patients and methodsAn observational cross-sectional study conducted by 92 allergy specialists who were asked to complete a registry entry for all patients consulting consecutively for a first AIT prescription during two periods (autumn and spring) between September 2021 and June 2022. Doctors were asked to provide information on treatment methods and reasons for the prescription in patients having received at least one NPP and who were included in the cohort. ResultsAmong the 3410 patients in the registry (children [26%], adolescents [17%], adults [57%]), 99% were prescribed AIT for rhinitis and/or conjunctivitis (72%), and/or associated asthma (39%); 68% were prescribed an NPP exclusively (children [87%], adolescents [12%], adults [63%]). Among the 1111 patients in the cohort (children [36%], adolescents [12%], adults [52%]), 73% were poly-sensitised, 44% had asthma, and at least 24% had another allergic co-morbidity. The main reasons for choosing NPPs were flexibility of dosage (35%), unavailability of the tablet form (24%) and indication not available (17%). In patients eligible for the tablet, the remaining cost to be paid by the patient was the reason for the prescription in 22% of cases. ConclusionWhile allergen tablets remain the preferred choice given the far greater knowledge of their efficacy and tolerance, in clinical practice NPPs continue to play an important role in the treatment of respiratory allergies in France.

Randomised Placebo-Controlled Trial of Grass Pollen Allergen Tablet Immunotherapy for Seasonal Rhinitis: Clinical and Surrogate Outcomes and Early Time Course of Immunologic Changes

Randomised Placebo-Controlled Trial of Grass Pollen Allergen Tablet Immunotherapy for Seasonal Rhinitis: Clinical and Surrogate Outcomes and Early Time Course of Immunologic Changes

Critical appraisal of Timothy grass pollen extract GRAZAX in the management of allergic rhinitis.

Allergic rhinitis is one of the most common diseases of adult and pediatric age, associated with grass pollen (GP) allergy in >50% cases, with a consistent impact on quality of life of affected patients. A grass allergen tablet, containing standardized extract derived from Timothy grass (Phleum pratense) pollen and ~15 μg major allergen P. pratense (rPhl p 5), may be the future of allergen-specific immunotherapy (IT) for GP allergy. The aim of this review was to critically evaluate the role of Timothy GP extract IT for the management of allergic rhinitis. For this purpose, we have tried to analyze potential mechanisms of action at the basis of Timothy GP extract, we have reviewed efficacy studies to establish potential benefits and clinical response, and we have also evaluated safety and tolerability profiles and patient focus perspective, such as quality of life, satisfaction and acceptability, and compliance to this IT.

Health economic comparison of SLIT allergen and SCIT allergoid immunotherapy in patients with seasonal grass-allergic rhinoconjunctivitis in Germany.

BackgroundAllergoids are chemically modified allergen extracts administered to reduce allergenicity and to maintain immunogenicity. Oralair® (the 5-grass tablet) is a sublingual native grass allergen tablet for pre- and co-seasonal treatment. Based on a literature review, meta-analysis, and cost-effectiveness analysis the relative effects and costs of the 5-grass tablet versus a mix of subcutaneous allergoid compounds for grass pollen allergic rhinoconjunctivitis were assessed.MethodsA Markov model with a time horizon of nine years was used to assess the costs and effects of three-year immunotherapy treatment. Relative efficacy expressed as standardized mean differences was estimated using an indirect comparison on symptom scores extracted from available clinical trials. The Rhinitis Symptom Utility Index (RSUI) was applied as a proxy to estimate utility values for symptom scores. Drug acquisition and other medical costs were derived from published sources as well as estimates for resource use, immunotherapy persistence, and occurrence of asthma. The analysis was executed from the German payer’s perspective, which includes payments of the Statutory Health Insurance (SHI) and additional payments by insurants. Comprehensive deterministic and probabilistic sensitivity analyses and different scenarios were performed to test the uncertainty concerning the incremental model outcomes.ResultsThe applied model predicted a cost-utility ratio of the 5-grass tablet versus a market mix of injectable allergoid products of € 12,593 per QALY in the base case analysis. Predicted incremental costs and QALYs were € 458 (95% confidence interval, CI: € 220; € 739) and 0.036 (95% CI: 0.002; 0.078), respectively. Compared to the allergoid mix the probability of the 5-grass tablet being the most cost-effective treatment option was predicted to be 76% at a willingness-to-pay threshold of € 20,000. The results were most sensitive to changes in efficacy estimates, duration of the pollen season, and immunotherapy persistence rates.ConclusionsThis analysis suggests the sublingual native 5-grass tablet to be cost-effective relative to a mix of subcutaneous allergoid compounds. The robustness of these statements has been confirmed in extensive sensitivity and scenario analyses.Electronic supplementary materialThe online version of this article (doi:10.1186/s13601-015-0045-z) contains supplementary material, which is available to authorized users.

Efficacy and safety of ragweed sublingual immunotherapy in Canadian patients with allergic rhinoconjunctivitis.

BackgroundCurrently accepted therapies for ragweed allergy in North America consist of pharmacotherapy and subcutaneous allergen immunotherapy injections to treat symptoms. Allergen immunotherapy not only reduces symptoms and the need for pharmacotherapy but has also been shown to have disease-modifying potential. Recently, ragweed immunotherapy administered via sublingual allergen tablet has been approved in North America for treatment of allergic rhinitis with and without conjunctivitis.MethodsThis was an analysis of pooled data for a prespecified subgroup of Canadian subjects from two multicentre, randomized, double-blind placebo-controlled trials of ragweed sublingual tablet (SLIT-T; 6 and 12 Amb a 1-U of Ambrosia artemisiifolia) in patients aged ≥18y, with ragweed-induced allergic rhinoconjunctivitis (AR/C) with or without asthma. Randomized subjects used once-daily ragweed SLIT-T or placebo for at least 12 weeks before the ragweed season and for up to 52 weeks post-randomization. The primary efficacy endpoint was the total combined score (TCS) based on the sum of AR/C daily symptom score (DSS) and daily medication score (DMS) averaged over the peak season. Treatment effects on TCS, DSS, and DMS in the entire season were also assessed. Adverse events (AEs) were monitored to assess safety.Results337 Canadian subjects were randomized in the two trials. During the peak season, ragweed SLIT-T 6 and 12 Amb a 1-U significantly reduced TCS by 26% (difference, -2.46 score point; p = .0009) and 40% (difference, -3.75 score point; p < .0001), respectively. In the overall population (N = 961), TCS reductions with 6 and 12 Amb a 1-U were 20% and 23%, respectively (both p < .001). Clinically meaningful reductions in entire-season TCS in Canadians were similar to those during peak ragweed season. Dose-dependent reduction of DSS and DMS was also observed for ragweed SLIT-T 6 and 12 Amb a 1-U during the peak season and the entire season. Ragweed SLIT-T was well tolerated in Canadian subjects and the overall population. Adverse events were generally mild to moderate and transient, occurring early in treatment; no systemic allergic reaction/anaphylaxis was noted.ConclusionRagweed SLIT-T is an effective form of immunotherapy that provides symptomatic efficacy of AR/C with a favorable risk profile in Canadian and overall populations.Trial registrationClinicaltrials.gov identifiers NCT00783198 and NCT00770315.

Sublingual immunotherapy for aeroallergens: Status in the United States

Sublingual immunotherapy (SLIT) has been used in the treatment of allergic disease for nearly 30 years and is prescribed at least as frequently as subcutaneous immunotherapy (SCIT). Several large U.S. clinical trials using single allergen tablets (grass and ragweed) or extract solution (ragweed) have met their primary clinical efficacy outcome. In December, 2013 the Federal Drug Administration (FDA) Allergenic Products Advisory Committee favorably reviewed two grass tablet product formulations; the FDA usually follows the recommendations of their advisory committees. Industry-sponsored and investigator-initiated aeroallergen SLIT clinical trials conducted in the United States are the focus of this article. To provide a basis for evaluation of this treatment, SLIT mechanisms, pharmacokinetics, efficacy as reported in systematic reviews, and safety are also discussed. Practical considerations of SLIT in the clinical setting are reviewed. These include patient instructions and adherence, which appear to be as poor as SCIT. Estimated treatment costs based on U.S.-licensed allergen extract manufacturers' list prices and doses reported to be effective in studies using U.S.-licensed allergen extracts or the allergen immunotherapy practice parameters are presented. Unmet needs, which include unknown effective dose for many allergen extracts, optimal schedule (daily versus other) and timing of treatment initiation (perennial versus precoseasonal, ≥8 weeks before or just at the start of season), and whether epinephrine autoinjectors should be routinely prescribed for SLIT patients are discussed.

Grading local side effects of sublingual immunotherapy for respiratory allergy: Speaking the same language

Sublingual immunotherapy (SLIT) is increasingly used worldwide. Despite its safety being well ascertained, there is no universally accepted system to grade and classify its adverse events (AEs). According to the literature, it seems reasonable to classify and grade systemic side effects by using the previously published World Allergy Organization recommendations. On the other hand, local side effects are the most frequent with SLIT, sometimes leading to its discontinuation. Therefore grading of the severity of local side effects was perceived as necessary for the purpose of uniform reporting, classification, and quantification of this aspect. AWorld Allergy Organization Taskforce, after examining the available literature and the postmarketing surveillance data, proposed a clinically based grading of the severity of local AEs caused by SLIT. The use of the Medical Dictionary for Regulatory Activities nomenclature for AEs was also included in this context. The proposed grading system for SLIT-induced local reactions is expected to improve and harmonize surveillance and reporting of the safety of SLIT.

Multiple-allergen and single-allergen immunotherapy strategies in polysensitized patients: Looking at the published evidence

In allergen immunotherapy there is debate as to whether polysensitized patients are best treated with many allergens simultaneously (chosen according to the sensitization profile, a predominantly North American approach) or a single allergen (chosen according to the most clinically problematic allergy, a predominantly European approach). In patients seeking treatment for moderate-to-severe respiratory allergies, polysensitization is more prevalent (range, 50% to 80%) than monosensitization in both the United States and Europe. Safe, effective, single-allergen preparations will most likely have been tested in polysensitized patients. In robust, large-scale clinical trials of grass pollen sublingual tablets, polysensitized patients benefited at least as much from allergen immunotherapy as monosensitized patients. A recent review of multiallergen immunotherapy concluded that simultaneous delivery of multiple unrelated allergens can be clinically effective but that there was a need for additional investigation of therapy with more than 2 allergen extracts (particularly in sublingual allergen immunotherapy). More work is also required to determine whether single-allergen and multiallergen immunotherapy protocols elicit distinct immune responses in monosensitized and polysensitized patients. Sublingual and subcutaneous multiallergen immunotherapy in polysensitized patients requires more supporting data to validate its efficacy in practice.

Specific immunotherapy in children

Subcutaneous immunotherapy (SCIT) with allergen extracts in children with allergic rhinitis, with or without co-seasonal asthma, has developed into a routine treatment although the scientific evidence for its efficacy is not as strong as for adults. In the hands of experienced allergists, this treatment has been proven to be safe. The development of allergen tablets for sublingual immunotherapy (SLIT) may open a new age of more convenient, safer SIT. In children, in particular, the evidence for the long-term efficacy of SLIT, its ability to prevent the development of asthma and polysensitization and its comparability to SCIT will be required before it will replace the traditional subcutaneous route. Issues of compliance represent an important drawback of SLIT. We need ways of improving this. Treatment of asthma by immunotherapy is still restricted to clearly defined patients with mild to moderate asthma with symptoms that are related to the specific allergen sensitization. In these patients, symptoms and use of anti-inflammatory therapy can be reduced by SIT.

Immuntherapie im Kindesalter

Allergen-specific imunotherapy (SIT) is the only treatment that interferes with basic pathophysiological mechanisms of allergic disease. New data demonstrates a role of SIT not only as a therapeutic agent but also as a preventive strategy to reduce onset of new sensitization and progression from allergic rhinitis to asthma. SIT is the only treatment that affects the natural course of the allergic disease and therefore should be started early in childhood. Data of SIT in children under the age of 5 is rare however. There is a need for studies investigating the primary and secondary preventive effect in very young children. Future research also needs to focus on treatment of atopic dermatitis and food allergy with SIT. Sublingual immunotherapy (SLIT) is a promising new modality of SIT since it has a good safety profile and is patient-friendly. The results of paediatric SLIT studies are heterogeneous and meta-analyses do not allow general recommendations for SLIT in childhood. New data however demonstrates that high dose of grass allergen tablets in children is capable to reduce symptom and medication scores in a same magnitude as observed in adults previously. New SLIT studies using high dose of other seasonal and perennial allergens as well as trials in children with asthma are required in order to define indications for SLIT in childhood. Furthermore, follow-up trials are needed to further elucidate the long-term effect and preventive capacity of SLIT in children.

Evaluation of a compliance device in a subgroup of adult patients receiving specific immunotherapy with grass allergen tablets (GRAZAX ®) in a randomized, open-label, controlled study: An a priori subgroup analysis

Objectives: This a priori subgroup analysis was conducted to assess patients' experience with a compliance device for the administration of sublingual specific immunotherapy for grass pollen-induced rhinoconjunctivitis. Methods: The present paper reports the results of a subgroup analysis of a multicenter, randomized, controlled, open-label European study in which adults with grass pollen-induced rhinoconjunctivitis received once-daily treatment with grass allergen tablets with or without a device to aid compliance. Treatment was given ~6 to 12 weeks before the grass pollen season, during the season (~8–10 weeks), and for up to 2 weeks after the end of the season. In the subgroup analysis, patients from Germany and the Netherlands who had been randomized to receive the compliance device were asked to complete a brief questionnaire at the final study visit. The questionnaire included 6 items concerning patients' use of the device and whether it helped them remember to take their tablets. Results: Of the 91 patients from Germany and the Netherlands who were randomized to use the compliance device along with grass allergen tablets, 71 returned the questionnaire. Among responders, 58 of 71 (82%) reported using the device sometimes or always, 50 of 63 (79%) found the device easy to use, 32 of 69 (46%) found that the device made it easier to remember to take tablets, and 43 of 71 (61%) indicated that they would consider using the device again. Conclusion: Most patients in this subgroup analysis used the compliance device as a medication reminder and rated it easy to use.

Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy

Immunotherapy with the SQ-standardized grass tablet Grazax is efficacious and well-tolerated in adult patients with rhinoconjunctivitis. Allergic asthma and rhinoconjunctivitis are closely linked, and a strategy combining treatment of the upper and lower airways is recommended. To investigate the efficacy of treatment with the grass tablet on grass pollen-induced rhinoconjunctivitis and asthma as well as the immunologic response and the safety profile in children. A total of 253 children age 5 to 16 years, with grass pollen-induced rhinoconjunctivitis with/without asthma, were randomized 1:1 to active treatment or placebo. Treatment was initiated 8 to 23 weeks before the start of the grass pollen season 2007 and continued throughout the entire season. Symptomatic medication was provided as relief medication to both groups in a stepwise fashion. Primary endpoints were rhinoconjunctivitis symptom and medication scores. The rhinoconjunctivitis symptom and medication scores and the asthma symptom score were all statistically significantly different between the 2 treatment groups. The differences in medians relative to placebo were 24%, 34%, and 64% in favor of active treatment. The immunologic response was similar to that observed in adults. The most common adverse reaction was oral pruritus, reported by 40 subjects (32%) in the active and 3 (2%) in the placebo group. Six subjects withdrew because of adverse events. No serious adverse events were assessed as treatment-related. Immunotherapy with the grass tablet reduced grass pollen-induced rhinoconjunctivitis and asthma symptoms in a pediatric population and introduced an immunomodulatory response, consistent with treatment of the underlying allergic disease. The treatment was well tolerated.

Sublingual immunotherapy: what have we learnt from the ‘big trials’?

Recent systematic reviews support the use of sublingual immunotherapy for allergic rhinoconjunctivitis in adults, whereas data in children have been less convincing. The present review evaluates three recent 'definitive' trials in adults and one in children. Two large independent randomized controlled trials of grass allergen tablets have confirmed the efficacy of sublingual immunotherapy in adults with seasonal allergic rhinoconjunctivitis. Effects were both allergen dose-dependent and time-dependent. Tablets were well tolerated and equally effective in monosensitized compared with polysensitized patients and in patients with peak seasonal asthma (patients with perennial asthma were specifically excluded). Local side effects were common but largely self-limiting and not bothersome. There were no serious treatment-related adverse events. Results were similar in magnitude to those observed in a comparable study of subcutaneous immunotherapy using an alum-based vaccine. A trial of sublingual drops in children with hayfever in a primary care setting was negative, although these results could not be generalized. Sublingual immunotherapy represents an effective and well tolerated treatment for seasonal allergic rhinoconjunctivitis in adults. Current ongoing paediatric trials and evaluation of long-term effects in adults will further define its role in therapy.

Phase III Trial with Grass Allergen Tablet for Sublingual Immunotherapy in Children

Specific immunotherapy with once-daily grass allergen tablet 75,000 SQ-T (2,800 BAU)(Grazax® Phleum pratense, ALK-Abelló A/S) is efficacious and well-tolerated in adult rhinoconjunctivitis patients. Recently, the tolerability of Grazax has also been demonstrated in Phase I trials in children. The present phase III study investigated both the efficacy and safety in children.

The Long-Term Efficacy and Safety of a Grass Allergen Tablet for Sublingual Immunotherapy: Findings from a 3-yr Clinical Trial

The Long-Term Efficacy and Safety of a Grass Allergen Tablet for Sublingual Immunotherapy: Findings from a 3-yr Clinical Trial

Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years

This is an interim analysis of a randomized, double-blind, placebo-controlled phase III trial with 3 years of daily treatment with grass tablet immunotherapy (GRAZAX; ALK-Abelló A/S, Hørsholm, Denmark) or placebo, followed by 2 years of follow-up to assess the persistent efficacy. We sought to evaluate the efficacy and safety of specific immunotherapy with grass allergen tablets compared with placebo after treatment covering 2 consecutive grass pollen seasons. The interim analyses included 351 adult participants with moderate-to-severe allergic rhinoconjunctivitis caused by grass pollen. Participants were treated with active (n = 189) or placebo (n = 162) tablets for an average of 22 months. All participants were allowed to use symptomatic rescue medication. The primary efficacy analysis showed highly significant mean reductions of 36% in rhinoconjunctivitis symptom score (P < .0001; median reduction, 44%) and 46% in rhinoconjunctivitis medication score (P < .0001; median reduction, 73%) in the active group relative to the placebo group. Mean rhinoconjunctivitis quality of life was 33% better (P < .0001; median, 40%). Clinical improvements were paralleled by significant changes in allergen-specific immunoglobulins. The treatment was well tolerated, and adverse events led to withdrawal in less than 1% of participants. There were no serious adverse events related to treatment. Grass allergen tablet immunotherapy showed progressive immunologic changes and highly significant efficacy over 2 years of continued treatment.

Sublingual Immunotherapy With Once-Daily Grass Allergen Tablets: A Randomized Controlled Trial in Seasonal Allergic Rhinoconjunctivitis

Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. J Allergy Clin Immunol. 2006;117:802–809 PURPOSE OF THE STUDY. To examine the efficacy and safety of sublingual immunotherapy (SLIT) in seasonal allergic rhinoconjunctivitis using timothy-grass–allergen tablets. STUDY POPULATION. The study included 855 patients aged 18 to 65 from 55 centers in Canada and Europe with seasonal allergic rhinoconjunctivitis induced by grass pollen. METHODS. A double-blind, randomized, parallel-group, placebo-controlled trial was conducted during 2002–2003. Patients had a history of allergic rhinoconjunctivitis during grass-pollen season for at least 2 years with a positive skin-prick–test result and serum-specific immunoglobulin E (IgE) to Phleum pratense. Individuals were randomly assigned to receive placebo or 2500, 25 000, or 75 000 SQ-T sublingual tablets administered daily. Daily diaries of symptoms (0–3) and rescue-medication use from pre–through post–grass-pollen season were kept, and a rhinoconjunctivitis quality-of-life (QoL) questionnaire was completed. Well days were calculated as those with a symptom score of ≤2 and no rescue-medication use. RESULTS. A total of 790 (92%) participants completed the trial that included a mean duration of treatment of 18 weeks. Treatment with 75 000 SQ-T tabs revealed an improvement in symptom score (16%; P = .0710) and medication score (28%; P = .0470) when compared with placebo. The QoL score and number of well days also revealed improvement of 17% (P = .006) and 18% (P = .041), respectively. The 2 lower doses did not demonstrate significant change from placebo. Preseason treatment for 8 weeks with the 75 000 SQ-T dose showed an increased improvement of symptom score (21%; P = .002) and medication score (29%; P = .012) compared with placebo. In the 75 000 SQ-T group, specific IgG to P pratense was increased after 8 weeks of treatment and tripled posttreatment. Specific IgE levels increased after treatment initialized but remained unchanged thereafter. Therapy was well tolerated with only mild-to-moderate symptoms (consisting of primarily oral pruritis and throat irritation) noted in 53% of the patients. CONCLUSIONS. Grass-pollen SLIT has a dose-dependent efficacy, is well tolerated, and provides improved QoL for patients with seasonal allergic rhinoconjunctivitis. REVIEWER COMMENTS. SLIT for grass-pollen allergy holds promise as an alternative future therapy to subcutaneous immunotherapy that is attractive on many levels. Grass-pollen SLIT may have broader coverage range because of improved accessibility and more convenient administration, less discomfort than injections, and decreased risk of IgE-mediated severe systemic reactions. Preseason coverage with SLIT may improve symptoms and reduce medication requirements for treatment of seasonal allergic rhinoconjunctivitis.

Efficacy and safety of grass allergen tablets in patients with grass pollen rhinoconjunctivitis of differing severity profiles

Efficacy and safety of grass allergen tablets in patients with grass pollen rhinoconjunctivitis of differing severity profiles

SQ-standardised grass (phleum pratense) allergen tablet improves disease specific quality of life in adult patients with grass pollen induced rhinoconjunctivitis over 2 years of continuous treatment

SQ-standardised grass (phleum pratense) allergen tablet improves disease specific quality of life in adult patients with grass pollen induced rhinoconjunctivitis over 2 years of continuous treatment