Standardized allergen extracts for allergen immunotherapy.

Nineteen U.S. allergen extracts were standardized by the U.S. Food and Drug Administration (FDA) between 1987 and 1998, including of two house-dust mites, short ragweed, cat hair and cat pelt, seven temperate and one southern grass, and six Hymenoptera venom preparations. Relevant literature was reviewed. For each allergen, a "representative" extract was established; the potency of each representative extract was determined by measurement of the total protein content (Hymenoptera venom), radial diffusion measurement of the dominant allergen (short ragweed and cat), or, if there was no dominant allergen, then by quantitative skin testing by using the ID50EAL (intradermal dilution for 50 mm sum of erythema determines the bioequivalent allergy units) method. In vitro tests were developed to allow the manufacturer to demonstrate that each lot of its extract was statistically identical, within defined limits, to the FDA reference extract. These tests included radial immunodiffusion, competitive enzyme-linked immunosorbent assay, and isoelectric focusing. The standardized extracts offer the advantage of consistent potency from lot to lot for each manufacturer and also from manufacturer to manufacturer, and assure the presence of recognized significant allergens within the extract. Therefore, standardized extracts offer improved safety and efficacy over their nonstandardized predecessors.

Recent development on the use of sublingual immunotherapy tablets for allergic rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is an immunoglobulin (Ig) E-mediated inflammatory condition that causes sneezing, nasal congestion, rhinorrhea, and nasal itch. Although subcutaneous immunotherapy for the treatment of AR has been in use and well established as a treatment modality, sublingual immunotherapy (SLIT) is increasingly considered to be the safer and more convenient alternative. Thus, the objective of this review is to describe recent findings pertaining to the use of SLIT tablets (SLIT-T) for AR. DATA SOURCES: A database search (PubMed.gov) for articles published between January 1, 2017, and February 9, 2021, was conducted using the following key words: "allergic rhinitis," AND-ed "sublingual immunotherapy." Included were randomized placebo-controlled trials. Other experimental design studies were excluded. STUDY SELECTIONS: A total of 11 randomized placebo-controlled trials were selected for full-text review and included in the analysis. All studies investigated the use of SLIT on patients with seasonal AR (4 tree pollen, 1 grass pollen, and 1 Japanese cedar) or perennial AR (3 house dust mite). RESULTS: Our review of 7 recently published randomized placebo-controlled trials with 2348 subjects receiving SLIT reported increased efficacy, safety, supportive immunologic parameters (IgE and IgG4 pre- and posttreatment levels), and improved quality of life. All studies excluded subjects with overlapping seasonal or perennial allergens, a history of moderate-to-severe uncontrolled asthma, or reduced lung function. CONCLUSION: Our review highlights that SLIT is a safe and effective treatment that considerably reduces symptoms and medication requirements in AR and improves quality of life.

Allergenicity at component level of sub-pollen particles from different sources obtained by osmolar shock: A molecular approach to thunderstorm-related asthma outbreaks.

BACKGROUND: The so-called "thunderstorm asthma" (TA) is an uncommon but dramatic outbreak of asthma attacks occurring during a thunderstorm in the pollen and moulds season. Mechanisms which make the pollen able to enter the deeper airways and provoke severe asthma symptoms are still unclear. OBJECTIVE: To test the hypothesis that sub-pollen particles (SPPs) originated from the rupture by an osmotic shock of pollen associated with TA contain allergens. METHODS: After hydration, SPPs released from pollen grains of grass, pellitory, olive, cypress, ragweed and birch were isolated and determined by microscopy. Allergens were determined by in vitro ELISA inhibition tests indirectly using the sera from 10 polyreactive patients. An inhibition <50% was considered as negative, 50%-75% moderate and > 75% complete. RESULTS: The inhibition experiments showed that the SPPs from birch and cypress were unable to inhibit serum IgE reactivity to Bet v 1 and Cup a 1, respectively. Ragweed SPPs inhibited ragweed pollen extract and Amb a 1 by 75.8 ± 0.11% and 81.2 ± 0.15%, respectively. Olive and pellitory SPPs retained almost the whole IgE-binding capability in all cases tested. Grass SPPs inhibited 32 ± 0.06% of Lolium perenne Lol p 1 and 65% of Phleum pratense extracts, but results were highly variable for individual allergens (97.5%-0.03% for Phl p 2, 45.3 ± 0.12% for Phl p 5, 24.7 ± 0.22% for Phl p 6, and 38.3 ± 0.2% for Phl p 1). CONCLUSIONS: Inhibition experiments confirm the hypothesis that SSPs obtained after the osmotic shock of pollen involved in TA, namely grass, pellitory and olive tree pollen, contain allergens and therefore they can induce severe asthma attacks during thunderstorms.

Experimental Mouse Models of Ragweed- and Papain-Induced Allergic Conjunctivitis.

Mouse models of allergic conjunctivitis mimic various aspects of human allergic conjunctivitis. They are useful as acute models of allergic conjunctivitis to study immunological aspects of this condition. In this chapter, we will describe ragweed-pollen-induced experimental allergic conjunctivitis (mostly driven by adaptive immunity), and papain-soaked contact lens-induced experimental allergic conjunctivitis (mostly driven by innate immunity). Giemsa staining of histological sections is used for quantification of the number of infiltrating eosinophils, which is useful to evaluate the severity of the allergic inflammation. Immunohistochemical staining and quantitative PCR are used to clarify spatiotemporal expression of proinflammatory molecules in the conjunctival tissue. Flow cytometric analysis of conjunctival tissue is used for the detection of innate lymphoid cell type 2 (ILC2) in the ocular surface tissues.

Purification and biochemical characterization of Hel a 6, a cross-reactive pectate lyase allergen from Sunflower (Helianthus annuus L.) pollen.

Sunflower pollen was reported to contain respiratory allergens responsible for occupational allergy and pollinosis. The present study describes the comprehensive characterization of a major sunflower allergen Hel a 6. Natural Hel a 6 was purified from sunflower pollen by anion exchange and gel filtration chromatography. Hel a 6 reacted with IgE-antibodies from 57% of 39 sunflower-sensitized patient sera suggesting it to be a major allergen. The patients were of Indian origin and suffering from pollinosis and allergic rhinitis. Hel a 6 exhibited allergenic activity by stimulating mediator release from basophils. Monomeric Hel a 6 displayed pectate lyase activity. The effect of various physicochemical parameters such as temperature, pH, and calcium ion on the functional activity of Hel a 6 revealed a stable nature of the protein. Hel a 6 was folded, and its melting curve showed reversible denaturation in which it refolded back to its native conformation from a denatured state. Hel a 6 displayed a high degree of sequence conservation with the pectate lyase allergens from related taxonomic families such as Amb a 1 (67%) and Art v 6 (57%). The IgE-cross reactivity was observed between Hel a 6 and its ragweed and mugwort homologs. The cross-reactivity was further substantiated by the mediator release when Hel a 6-sensitized effector cells were cross-stimulated with Art v 6 and Amb a 1. Several putative B cell epitopes were predicted and mapped on these 3 allergens. Two antigenic regions were found to be commonly shared by these 3 allergens, which could be crucial for cross-reactivity. In conclusion, Hel a 6 serves as a candidate molecule for diagnosis and immunotherapy for weed allergy.

Effect of perennial dust mites allergy on symptom severity of autumn allergic rhinitis in adults.

Background: Multiple immunoglobulin E (IgE) mediated sensitizations and/or allergies often coexist in patients with allergic rhinitis (AR). Several simultaneous allergen exposures in multiple IgE-mediated sensitizations and/or allergies may increase the allergen load and be related to disease severity. No study has verified whether positive allergen serum IgE levels and allergen categories together are associated with AR severity in adults. Objective: To investigate the effects of perennial dust mites (DMs) allergy and multiple serum sIgE-mediated autumn pollen allergy coexistence on symptom severity in adult patients with AR in autumn. Methods: In total, 153 patients with AR and with autumn pollen allergy (Artemisia argyi, ragweed, and hop) with or without DMs allergy were recruited in the autumn pollen season. Symptom severity was assessed by using the Chinese version of the visual analog scale (VAS): four rhinitis symptoms (sneezing, rhinorrhea, nasal pruritus, and nasal congestion) and two ocular symptoms (ocular itching and/or grittiness and/or redness, and ocular tearing) were scored at approximately the same period. We measured allergen serum sIgE levels for the inhaled allergens. The effects of DMs allergy and multiple autumn pollen allergy coexistence on symptom severity were analyzed. Results: Neither the sum of the autumn pollen allergens categories (total number of positive autumn pollen allergens, i.e., Artemisia argyi or ragweed or hop positive: 1; Artemisia argyi and ragweed positive: 2; Artemisia argyi, ragweed, and hop positive: 3) nor serum sIgE levels( total sIgE levels of positive autumn pollen allergens) exerted any influence on the severity of nasal and ocular symptoms (p > 0.05). When the concomitant DMs allergy status was considered, the sum of the positive autumn pollen allergen categories and accumulated positive autumn pollen and DMs serum sIgE levels (total levels of serum sIgE of positive autumn pollen allergens plus the levels of serum sIgE of DMs) had no influence on patients' symptom severity (p > 0.05). Conclusion: The coexistence of perennial DMs allergy and multiple autumn pollen allergy did not affect the severity of symptoms among adult patients with AR and with autumn pollen allergy in autumn.

Allergic Rhinitis to Weed Pollen in Germany: Dominance by Plantain, Rising Prevalence, and Polysensitization Rates over 20 Years.

BACKGROUND: In contrast to the 3 major aeroallergens tree pollen, grass pollen, and house dust mites, allergic rhinitis caused by herbal pollen has received comparatively little attention in recent clinical studies. Since various weeds flower during summer until fall, allergic rhinitis to weeds may be underdiagnosed and/or mistakenly diagnosed as grass pollen allergy. OBJECTIVE: To investigate (i) the currently most frequent weed allergy between mugwort, ragweed, plantain, chamomile, nettle, and oilseed rape and (ii) time trends in prevalence of sensitization to weed pollen in the middle of Germany over the last 20 years. METHODS: This study, the largest of its kind to date, monocentrically evaluated the prick test results of a total of 6,220 patients with suspected RCA over a period of 20 years (1998-2017). RESULTS: In the study cohort, sensitization rates to plantain almost doubled from 26.6% in the decade 1998-2007 to 50.5% in 2008-2017. Identical increases were observed for ragweed, while sensitization rates for mugwort stayed largely unchanged. The most prominent increase in positive skin prick tests to plantain and ragweed pollen was mainly observed in younger patients. Further, we identified a trend toward polysensitization, currently dominated by plantain and ragweed. Sensitization to weed pollen was found to be highly associated with additional sensitizations to grass and/or birch pollen. CONCLUSION: Plantain is currently the best choice to screen rhinitis patients for weed allergy which identifies 86% of all weed-sensitized individuals, at least in Germany. Over the last 20 years, we demonstrate a significant rise in the total number of weed pollen sensitization as well as increases in polysensitization, predominantly in younger patients.

At-a-glance - Pollens, climate and allergies: Quebec initiatives. / Aperçu - Pollens, climat et allergies : initiatives menées au Québec.

Pollen allergies are a major source of seasonal allergic rhinitis in North America. This type of rhinitis affects 17% of adults in Quebec, a marked increase in the last 30 years. Ragweed (Ambrosia artemisiifolia L.) pollens are responsible for 50% to 90% of rhinitis cases. Climate change has played a significant role in the increased prevalence of seasonal allergic rhinitis over the last few decades. In 2015, the Quebec government put in place a strategy to tackle this problem, the Stratégie québécoise de réduction de l'herbe à poux et des autres pollens allergènes [Quebec strategy to reduce ragweed and other allergenic pollens]. Based on solid evidence, the Strategy advocates for co-operation between stakeholders and the integration of control measures into the maintenance practices of municipalities and other large public and private landowners. This article presents the scientific data underpinning the Strategy and initial successes of the action taken under the Strategy.

Climate change increases the quantities and allergenic potential of ragweed pollen. Seasonal allergic rhinitis caused by these pollens has increased significantly in North America. Simple environmental control methods can clinically decrease the impact of ragweed pollen. A coordinated policy that incorporates these control measures in municipalities' groundskeeping practices is being implemented in Quebec.

Les changements climatiques augmentent les quantités et le potentiel allergène du pollen de l'herbe à poux (ambroisie). La rhinite allergique saisonnière liée à ces pollens est en augmentation marquée en Amérique du Nord. Des moyens de contrôle environnemental simples peuvent diminuer cliniquement l'impact du pollen de l'herbe à poux. Une politique concertée qui intègre des mesures de contrôle dans les pratiques d'entretien des terrains par les municipalités est en implantation au Québec.

Clinical standardization of two controlled allergen challenge facilities: The Environmental Exposure Unit and the Biogenics Research Chamber.

BACKGROUND: Controlled allergen challenge facilities (CACF), in disparate geographic regions with dissimilar engineering and base populations, have historically functioned as single, independent sites in clinical allergy trials. We aimed to demonstrate "between-unit reproducibility" to allow controlled challenge trials of participants using 2 CACFs. OBJECTIVE: To compare and standardize 2 CACFs located in Kingston, Ontario, Canada, and San Antonio, Texas, by examining participant-reported symptom severity during qualifying and treatment visits and evaluating response to treatment, while using the same allergen. METHODS: At 2 different CACFs, participants were enrolled in a double-blind, placebo-controlled, crossover intervention trial with cetirizine 10 mg. Different distribution devices delivered common short ragweed pollen via laminar air flow and maintained an airborne concentration of 3500 ± 700 grains/m3 in both facilities. A 1-hour "sham" run with no pollen release preceded a priming exposure of 3 hours and was followed 3 days later by a qualifying/treatment 5-hour exposure. At least 14 days later, another priming exposure was followed by the crossover exposure and treatment. RESULTS: Forty-eight and 43 subjects completed the study at Kingston and San Antonio, respectively. Demographics were similar. Fewer than 10% exhibited symptoms with sham exposure. No significant differences were found between the 2 facilities in maximal total rhinoconjunctivitis symptom score, total nasal symptom score, and total ocular symptom score, nor in areas under the curve. In both facilities, no significant effects of cetirizine 10 mg over placebo were detected. CONCLUSION: The results were equivalent, demonstrating that the 2 CACFs can be used together in dual-center clinical trials and show the possibility of multicenter trials involving multiple CACFs.

Clinical Characteristics of Oral Allergy Syndrome in Children with Atopic Dermatitis and Birch Sensitization: a Single Center Study.

BACKGROUND: Oral allergy syndrome (OAS) is an immunoglobulin E (IgE)-mediated hypersensitivity that occurs frequently in older children with pollen sensitization. This study focused on the clinical characteristics of OAS in children with atopic dermatitis (AD) and birch sensitization. METHOD: s: A total of 186 patients aged 2-18 years with AD and birch sensitization were enrolled in this study between January 2016 and March 2017. Their levels of serum total IgE and birch- and ragweed-specific IgE (sIgE) were measured using ImmunoCAP (Thermo Fisher Scientific, Uppsala, Sweden). Information regarding causative foods and symptoms were obtained via interviews. The patients were divided into 3 groups according to their ages (group 1, 2-6 years; group 2, 7-12 years; and group 3, 13-18 years). RESULTS: Eighty-one of the 186 (43.5%) children with AD who were sensitized to birch pollen were diagnosed as having OAS. The prevalence of OAS in group 1 (the children who had AD and birch sensitization aged 2-6 years) was 36.6%. A greater predominance of men was noted in the non-OAS group (77.1%) compared to the OAS group (60.5%). Apples were the most common causative food in group 2 and 3 while kiwis were the most common cause of OAS in group 1. There was a statistically significant correlation between birch-sIgE levels and the prevalence of OAS (P = 0.000). The cut-off value was 6.77 kUA/L with 55.6% sensitivity and 79.0% specificity (area under the curve 0.653). CONCLUSION: In our study, the prevalence of OAS in children with AD and birch sensitization was 43.5%. Even in the preschool age group, the prevalence of OAS was considerable. Patients with high levels of birch-sIgE were more likely to have OAS. Clinicians should therefore be vigilant about OAS in patients with a high degree of sensitization to birch pollen and even young children if they have birch sensitization.

Human cystatin SN is an endogenous protease inhibitor that prevents allergic rhinitis.

BACKGROUND: Protease allergens disrupt epithelial barriers to exert their allergenicity. Cystatin SN (encoded by CST1) is an endogenous cysteine protease inhibitor upregulated in nasal epithelia in patients with allergic rhinitis (AR). OBJECTIVE: We sought to investigate the protective effect of human cystatin SN on AR symptoms using pollen-induced AR mouse models. METHODS: We performed an in vitro protease activity assay to evaluate the effect of recombinant human cystatin SN (rhCystatin SN) on Japanese cedar (JC) or ragweed proteases. A human nasal epithelial cell line, RPMI 2650, was used to examine tight junction (TJ) disruption in vitro. Mice were sensitized and nasally challenged with JC or ragweed pollens with or without rhCystatin SN to examine the effect of rhCystatin SN on AR symptoms and the epithelial barrier in vivo. Because mice lack CST1, we generated transgenic (Tg) mice expressing human CST1 under control of its genomic control region (hCST1-Tg mice) to examine the role of cystatin SN in physiologically expressed conditions. RESULTS: rhCystatin SN inhibited JC but not ragweed protease activities and prevented JC-induced but not ragweed-induced TJ disruption in vitro. Exogenous administration of rhCystatin SN ameliorated JC-induced but not ragweed-induced sneezing and nasal TJ disruption in vivo. Furthermore, hCST1-Tg mice showed decreased JC-induced but not ragweed-induced sneezing symptoms and nasal TJ disruption compared with wild-type mice. CONCLUSION: Human cystatin SN suppresses AR symptoms through inhibiting allergen protease activities and protecting the nasal TJ barrier in an allergen-specific manner. We propose that upregulation of nasal endogenous protease inhibitors, including cystatin SN, is a novel therapeutic strategy for protease allergen-induced AR.

Ragweed allergy immunotherapy tablet MK-3641 (Ragwitek®) for the treatment of allergic rhinitis.

INTRODUCTION: Allergic rhinitis (AR) is among the most common chronic conditions affecting both children and adults. It is the cause of significant morbidity from the symptoms and interference with sleep. It results in major impairment of performance both at school and at work. In the U.S. and certain parts of Europe, ragweed pollen is a major cause of seasonal AR. In 2014, the U.S. Food and Drug Administration (FDA) approved a sublingual ragweed tablet (MK-3641) for use in adults with ragweed-induced AR. Areas covered: This paper will review the impact of ragweed-induced AR and available treatments including subcutaneous immunotherapy and studies with MK-3641. The principal search method was PubMed. Expert commentary: One dosing finding, two 28-day safety and two 52-week safety and efficacy studies have been conducted with MK-3641. The 12-U (12µg Amb a 1) tablet was the most effective. Local application site reactions were common but usually not serious. Only one, non-serious systemic reaction was reported in four safety studies. MK-3641 is a safe and effective treatment for ragweed-pollen-induced AR when treatment is initiated ≥ 12 weeks prior to the onset of the ragweed pollen season.

Impacts of long-term ragweed pollen load and other potential risk factors on ragweed pollen allergy among schoolchildren in Hungary.

INTRODUCTION AND OBJECTIVE: Hungary is one of the areas in Europe most infected with ragweed (Ambrosia artemisiifolia L.) and its pollen, and is the most important cause of seasonal allergic rhinoconjunctivitis in the country. The aim of the study was to investigate the association between ragweed pollen allergy and long-term ragweed pollen load, as well as analysis of the the impacts of additional potential risk factors on health outcomes. MATERIAL AND METHODS: A modified version of standardized questionnaires, based on the International Study of Asthma and Allergy in Childhood, were completed by the parents of schoolchildren aged 8 - 9 attending 3rd grade classes throughout the country. Pollen load was calculated for each settlement from daily ragweed pollen concentrations monitored by 19 monitoring stations in the country. Descriptive and analytical statistical methods were applied. RESULTS: At national level there was a significant inverse association between prevalence of ragweed allergy and its pollen load, but significance was lost after excluding data from Budapest, the capital city, due to the impact of urbanization. In the adjusted model, parental atopic disease was the strongest risk factor (either parent had atopic disease aOR=2.60; 95% CI=2.31-2.93 or both parents had atopic disease aOR=4.56; 95% CI=3.71-5.60). Further significant risk factors were male gender (aOR=1.52; 95% CI=1.36-1.71), lower respiratory infection in the first two years of life (aOR=1.91; 95% CI=1.70-2.16), and unshared children's room (aOR=1.22; 95% CI=1.09-1.37). Allergy was significantly less common among children whose parents received social aid (aOR=0.83; 95% CI=0.72-0.97) and whose mother smoked during pregnancy (aOR=0.80; 95% CI=0.64-0.99). CONCLUSIONS: Higher ragweed pollen exposure was not found to be associated with higher risk of ragweed allergy.

Modifiable Risk Factors for Common Ragweed (Ambrosia artemisiifolia) Allergy and Disease in Children: A Case-Control Study.

Ragweed allergy is a major public health concern. Within Europe, ragweed is an introduced species and research has indicated that the amounts of ragweed pollen are likely to increase over Europe due to climate change, with corresponding increases in ragweed allergy. To address this threat, improving our understanding of predisposing factors for allergic sensitisation to ragweed and disease is necessary, specifically focusing upon factors that are potentially modifiable (i.e., environmental). In this study, a total of 4013 children aged 2⁻13 years were recruited across Croatia to undergo skin prick tests to determine sensitisation to ragweed and other aeroallergens. A parental questionnaire collected home environment, lifestyle, family and personal medical history, and socioeconomic information. Environmental variables were obtained using Geographical Information Systems and data from nearby pollen, weather, and air pollution stations. Logistic regression was performed (clustered on school) focusing on risk factors for allergic sensitisation and disease. Ragweed sensitisation was strongly associated with ragweed pollen at levels over 5000 grains m⁻3 year−1 and, above these levels, the risk of sensitisation was 12⁻16 times greater than in low pollen areas with about 400 grains m⁻3 year−1. Genetic factors were strongly associated with sensitisation but nearly all potentially modifiable factors were insignificant. This included measures of local land use and proximity to potential sources of ragweed pollen. Rural residence was protective (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55⁻0.98), but the factors underlying this association were unclear. Being sensitised to ragweed doubled (OR 2.17, 95% CI 1.59⁻2.96) the risk of rhinoconjunctivitis. No other potentially modifiable risk factors were associated with rhinoconjunctivitis. Ragweed sensitisation was strongly associated with ragweed pollen, and sensitisation was significantly associated with rhinoconjunctivitis. Apart from ragweed pollen levels, few other potentially modifiable factors were significantly associated with ragweed sensitisation. Hence, strategies to lower the risk of sensitisation should focus upon ragweed control.

Ragweed sublingual tablet immunotherapy: part II - practical considerations and pertinent issues.

Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both efficacious and safe for the treatment of respiratory allergies such as allergic rhinoconjunctivitis or allergic asthma. Based on the clinical documentation of SLIT ragweed tablets, they have gained marketing authorization in the USA by the US FDA in 2014 for adult patients. Following clinical data from (pivotal) multicenter Phase II and III trials as performed in the USA and Canada and real life experience after registration in 2014, SLIT ragweed tablets can be recommended as efficacious and safe treatment option with disease modifying potential when adequately indicated and performed. Therefore, several practical issues should be considered for treating ragweed allergic patients with these tablets. This second part of a thorough review on ragweed SLIT tablets addresses important clinical questions which should be taken into account by the subscribing practitioner before initiation and during the treatment.

From allergen to oral vaccine carrier: A new face of ragweed pollen.

Oral delivery of vaccines is highly desirable, yet it has met with limited success. Previously we developed allergen-free pollen grains as a novel approach for oral vaccination. We showed that spores of Lycopodium clavatum can be used for oral vaccination. However, it is unknown if pollens of other species can be similarly used as an oral vaccine carrier. Therefore, in this study, we evaluated common ragweed (RW) pollen (Ambrosia elatior) for its oral vaccination potential. Allergen-free RW pollens were prepared from natural pollens through chemical treatment. Eight weekly oral doses of ovalbumin (OVA) formulated with treated RW generated strong systemic (anti-OVA IgG, IgG1, IgG2a, and IgA) and mucosal (anti-OVA IgA) immune responses that sustained for at least three months after vaccination. Mucosal IgA against OVA was found in the lung lavage, feces, saliva, and vaginal secretion. Moreover, three and half months after the last immunization OVA-specific plasma cells were found in the bone marrow that actively secreted IgG and IgG1 antibodies. No IgE against RW-specific proteins was detected in the serum. Overall, RW pollen demonstrated potential for oral vaccine delivery.

Ragweed sublingual tablet immunotherapy: part I - evidence-based clinical efficacy and safety.

Sublingual tablet immunotherapy provides an attractive alternative approach to allergen immunotherapy, as the allergen is administered as a rapidly dissolving sublingual tablet. Part I of this two-part series on the ragweed sublingual tablet describes the dose-ranging clinical work, the safety studies and the clinical outcomes from the pivotal trials which provide clear evidence for statistically significant and clinically meaningful benefit in the treatment of patients suffering from ragweed-induced seasonal allergic rhinitis-conjunctivitis with or without milder asthma. The robust results observed in the clinical trials performed with the ragweed sublingual tablet are defined by the quality of their study design, their use of a standardized allergen extract, their consistent reproducibility in demonstrating therapeutic efficacy and their properly quantified and graded safety data.