The use of environmental exposure chambers in studies related to ocular surface effects.

PURPOSE OF REVIEW: The potential of allergen challenges using environmental exposure facilities in allergic conjunctivitis drug development and more recently its implication on the diagnosis of the united airways concept have been emphasized in the recent literature. This study aims to present an overview of new and important data in this field. RECENT FINDINGS: Standardized methodologies for ocular surface assessment during allergen challenges were described. The Total Ocular Symptom Score (TOSS) is the main validated questionnaire used for the assessment of ocular surface during allergen challenges. It combines patient and investigator assessments for more accurate conjunctival response and was extensively used in clinical research and daily practice. Environmental Exposure Chambers (EECs) studies aim to conduct tight-controlled challenges to a stable and well defined allergen airborne concentration, closer to natural exposure to evaluate the efficacy of nonpharmaceutical and antiallergic treatments. Recent studies showed a good correlation between ocular symptoms elicited by EEC and those assessed during natural exposure. These validated methods allow to investigate the efficacy of novel pharmacotherapies for allergic conjunctivitis and allergen immunotherapy (AIT) in a real-world model of allergen exposure. SUMMARY: This study aims to summarize novel data regarding the impact of EECs in studying pathophysiology and drug efficacy in the context of existing clinical protocols related to ocular surface effects. In this regard, studies comparing conjunctival response during natural and EEC exposures in patients with pollen-induced conjunctivitis aimed to demonstrate better outcomes in tight-controlled exposures mimicking natural exposure. Because allergen challenges are widely implemented in allergy treatment, this article will focus on the most important outcomes and the evolution of treatments for allergic conjunctivitis.

Efficacy and safety of Artemisia annua sublingual immunotherapy in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons.

OBJECTIVE: This study investigates the efficacy and safety of sublingual immunotherapy (SLIT) with A. annua allergens in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons. METHODS: Seventy patients with moderate-severe seasonal allergic rhinoconjunctivitis were divided evenly into the SLIT and control groups. The SLIT last from 3 months before the summer-autumn pollen season in 2021 till the end of the summer-autumn pollen season in 2022. The daily individual symptom score, total rhinoconjunctivitis symptom score (dTRSS), total medication score (dTMS), combined score of medication and rhinoconjunctivitis symptom (dCSMRS), visual analog scale (VAS) score, and adverse events (AEs) were evaluated. RESULTS: The average pollen concentration in 2022 was twice that previous two-year during the pollen season. Fifty-six patients completed treatments (SLIT group: 29, control group: 27). Compared with baseline, the individual symptoms, dTRSS, dTMS, dCSMRS, and VAS scores of SLIT group declined in 2021. After 16 months of SLIT, all efficacy indexes in 2022 were still lower than baseline and equivalent to those in 2021. In control group, the efficacy indexes in 2022 were higher than that in 2020 and 2021. The efficacy indexes of SLIT group were lower than those of control group in 2021 and 2022. SLIT is effective for both mono- and poly-sensitized patients. AEs incidence in SLIT group was 82.7% without severe AEs. CONCLUSIONS: The A. annua-SLIT can obtain efficacy and safety over two pollen seasons for patients with moderate-severe seasonal allergic rhinoconjunctivitis.

Off-label Use of Oral Immunotherapy for Rhinoconjunctivitis and Asthma due to Grass Pollen: A Safe and Effective Alternative in Patients over 65 Years Old: A Series of Case Reports.

INTRODUCTION: Allergic rhinoconjunctivitis and asthma are the most common IgE-mediated diseases worldwide. Allergen-specific immunotherapy (AIT) is currently the only modifying treatment for these IgE-mediated diseases in both children and adults. Subcutaneous immunotherapy is widely used, but in patients over 65 years old, there may be an increased risk of adverse reactions and a worse response to treatment. Oral immunotherapy (OIT) has been proven to be effective and safe, but currently, in most countries, it has been licensed only for patients up to 65 years old based on its technical datasheet. So far, no studies on the efficacy and safety of this type of immunotherapy in patients older than 65 years old have been published. CASE PRESENTATION: We present four patients older than 65 years old with a diagnosis of moderate seasonal rhinoconjunctivitis and moderate-persistent seasonal pollen-induced asthma. Off-label use of oral immunotherapy (OIT) for grass pollen was prescribed due to the severity of their rhinoconjunctivitis symptoms and the worsening of asthma symptoms during the spring. Improvement in the rhinoconjunctivitis and asthma symptoms was reported by all patients since the first spring season and was maintained during the following two years of follow-up. There were no systemic reactions, and only two patients initially had self-limiting oral pruritus. CONCLUSION: Oral immunotherapy for pollens appears to be a convenient, effective, and safe option in older patients (>65 years) with comorbidities after a three-year treatment. This is, to the best of our knowledge, the first report on the off-label use of OIT in patients over 65 years old with symptoms of allergic rhinoconjunctivitis and asthma.

Safety and Effectiveness of a Single Multiallergen Subcutaneous Immunotherapy in Polyallergic Patients.

BACKGROUND: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. METHODS: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. RESULTS: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. CONCLUSIONS: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.

Treatment Effect of the Tree Pollen SLIT-Tablet on Allergic Rhinoconjunctivitis During Oak Pollen Season.

BACKGROUND: Birch, alder, hazel, and oak are members of the birch homologous group based on cross-reactivity toward the birch pollen allergen Betula verrucosa 1. Theoretically, allergy to these tree pollens may be treated by immunotherapy with one representative allergen extract. OBJECTIVE: To evaluate post hoc whether treatment of birch pollen-induced allergic rhinoconjunctivitis with a standardized tree sublingual immunotherapy (SLIT)-tablet containing birch pollen extract reduces symptoms and symptom-relieving medication use during the oak pollen season (OPS). METHODS: In a randomized, multinational, double-blind trial (EudraCT-2015-004821-15), 634 participants (ages 12-65 years) received daily tree SLIT-tablet (12 SQ-Bet) or placebo before and during tree pollen season (alder/hazel plus birch pollen season [BPS]). Symptom-relieving medication was allowed. The primary end point was the average total combined score (sum of rhinoconjunctivitis daily symptom score and daily medication score) during BPS. Outcomes during the OPS (excluding overlapping BPS days) were analyzed post hoc. RESULTS: Relative improvements in average total combined score, daily symptom score, and daily medication score with the tree SLIT-tablet versus placebo during the OPS were 25%, 22%, and 32%, respectively (all P < .001). Significant correlations were observed between birch and oak serum immunoglobulin E (sIgE) at baseline (r = 0.86) and between birch and oak IgG4 after treatment (r = 0.72). Oak sIgE and IgG4 kinetics in response to tree SLIT-tablet treatment were similar to birch. CONCLUSIONS: The tree SLIT-tablet leads to significant improvement of rhinoconjunctivitis outcomes during the OPS, supporting the clinical relevance of immunological cross-reactivity toward birch and oak allergens.

Intralymphatic immunotherapy improves grass pollen allergic rhinoconjunctivitis: A 3-year randomized placebo-controlled trial.

BACKGROUND: Allergic rhinoconjunctivitis is a global health problem. Different allergen immunotherapy regimes are marketed but have low adherence because they are expensive, complex, and time-consuming. New allergen immunotherapy forms are needed. OBJECTIVE: In a 3-year follow-up double-blind randomized placebo-controlled trial, we aimed to investigate the effect of intralymphatic allergen immunotherapy (ILIT). METHODS: Patients with grass pollen rhinoconjunctivitis were treated with 3 ILIT injections and an ILIT booster 1 year later, 3 ILIT injections and a placebo booster, or 3 placebo injections and a placebo booster. Primary outcome was improvement in a combined symptom and medication score (cSMS). A novel evaluation tool with a linear regression model of cSMS and grass pollen counts was developed. Secondary outcomes were changes in grass specific immunoglobulins and skin and nasal provocation tests to grass pollen. RESULTS: A total of 36 patients were included. Log10-transformed cSMS was reduced by 0.30 (95% CI, 0.11-0.49; P = .002), equaling 48.5% (95% CI, 24.5%-62%), in the entire 3-year follow-up period, significant only in the first follow-up season but not in the second and third seasons. The regression model showed a 37% (P < .001) reduction in cSMS. The booster injection 1 year later had no additional effect. Secondary, repeated measures of IgE and IgG4 to grass showed significant between-group difference and within-group change in the ILIT groups. No change in provocation test results was found. CONCLUSIONS: ILIT gives a substantial reduction in grass pollen allergy symptoms and use of rescue medication, significant in the first season after treatment. A booster injection had no additional effect.

Intradermal Phleum pratense allergoid immunotherapy. Double-blind, randomized, placebo-controlled trial.

BACKGROUND: In allergology, the intradermal approach is generally used to establish an aetiological diagnosis, with limited experience in specific allergen immunotherapy. OBJECTIVE: To evaluate the efficacy and safety of immunotherapy with an allergen extract of glutaraldehyde-polymerized Phleum pratense, administered intradermally, in patients with rhinoconjunctivitis sensitized to grass pollen. METHODS: Multicentre, randomized, double-blind, placebo-controlled clinical trial in patients from 12 to 65 years of age with rhinitis or rhinoconjunctivitis, with or without asthma, due to grass pollen allergy. Patients were divided into three groups and received a total of six doses in a weekly interval, of either placebo; 0.03 or 0.06 µg of protein per dose of P pratense allergoid. The primary objective was to evaluate the combined symptoms and medication consumption score (CSMS). The secondary objectives were symptoms and medication, tolerance to the conjunctival provocation test, specific IgE and IgG4 antibodies and the safety profile according to the WAO scale. RESULTS: The dose of 0.06 µg of protein proved to be effective versus the placebo by significantly reducing CSMS and increasing tolerance to the allergenic extract in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded. CONCLUSION & CLINICAL RELEVANCE: Intradermal immunotherapy with P pratense allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels.

Compliance in subcutaneous and sublingual allergen immunotherapy: A nationwide study.

INTRODUCTION: Allergic rhino-conjunctivitis is a highly prevalent condition. In moderate to severe cases, allergen immunotherapy (AIT) is a cost-effective therapeutic option. Previous data have reported a large difference in treatment compliance of subcutaneously (SCIT) and sublingually (SLIT) administered AIT. METHODS: By use of the unique civil registration number assigned to all Danish citizens and the Danish National Health Service Prescription Database, compliance rates of all patients prescribed with grass pollen AIT from January 1998 until December 2016 were analysed annually during the three-year treatment period. RESULTS: The male/female ratio was close to 1:1 in SCIT, while SLIT was more frequently used by men. A large proportion of users was children or adolescents (32% and 45%, SCIT and SLIT, respectively). Compliance of both subcutaneous and sublingual treatment gradually fell each year; compliance in year 3 was 57% and 53% for subcutaneous and sublingual treatment, respectively. Compliance of grass pollen sublingual treatment was also analysed each year after registration on the Danish market. Compliance significantly increased following the introduction and stabilised on a relatively high level. CONCLUSION: Based on previous studies, we hypothesised that AIT compliance would be low, especially in SLIT. However, in Denmark, compliance in SCIT and SLIT was almost similar, and the majority of patients completed the three-year treatment period with a compliance in the last quintile.

Small airways in children with allergic rhinoconjunctivitis: the potential role of a multicomponent nutraceutical.

Allergic rhinitis and asthma are closely linked. A progression from rhinitis to overt asthma is common. FEF25-75 is a spirometry parameter that could reflect small airways patency and could reliably predict early bronchial involvement in allergic rhinitis patients. MEF50 very strongly correlates with FEF25-75. The aim of this study was to evaluate possible spirometry change in two groups of children suffering from AR over time. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). The children were visited at baseline, at the end of the nutraceutical course, and after 1 year. FEV1, FVC, and MEF50 were the primary outcomes. After one year, children in AG had significantly higher MEF50 than CG children (p=0.009). In conclusion, the present study showed that a course with a multicomponent nutraceutical could prevent the MEF50 decline in children with allergic rhinoconjunctivitis.

Lertal®, a multicomponent nutraceutical, could reduce the use of antihistamines in children with allergic rhinoconjunctivitis.

Antihistamines are the cornerstone treatment of allergic rhinitis (AR). To quantify the antihistaminic consume is particularly relevant in clinical practice, since a remarkable use is usually associated with severe symptoms. The aim of the study was to measure the use of antihistamines in two groups of children suffering from AR. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). Both groups took antihistamines on demand. The children were visited at baseline and after 1 year. The number of days of antihistaminic use was the primary outcome. Children in AG had a significant reduced number of antihistamines use in comparison with CG (p=0.008). In conclusion, the current study showed that a course with a multicomponent nutraceutical could reduce the use of symptomatic antihistamines in children with allergic rhinoconjuncti- vitis.

Clinical assessment of tolerability, immunological and cutaneous reactivity effects of an abbreviated schedule with Olea europaeanative extract of subcutaneous immunotherapy.

Summary: Objectives. To evaluate the tolerability and efficacy of Olea europaea subcutaneous immunotherapy (SCIT) on patients with rhinoconjunctivitis. Methods. In this open clinical trial patients were assigned to an abbreviated build-up scheme. The outcomes were: number, percentage, and severity of adverse reactions. Secondary outcomes included: changes in immunoglobulin titers and changes in dose-response skin prick tests. Results. Only 8 systemic reactions were registered, which represented 7/47 (14.9%) of patients and 8/429 (1.9%) of administered doses. Regarding immunological parameters the significant increases of sIgG and sIgG4 evidenced the changes in the patient immune system. Cutaneous reactivity decreased significantly. Conclusions. Olea europaea SCIT (Allergovac® depot ROXALL Medicina España S.A.) showed a good safety and tolerability profile. Immunological changes with induction of blocking IgG and decreases in cutaneous reactivity were detected in the patients.

Safety and treatment compliance of subcutaneous immunotherapy: A 30-year retrospective study.

BACKGROUND: Safety and treatment compliance are still considered important shortcomings of subcutaneous immunotherapy (SCIT). OBJECTIVE: To assess the rate of side effects (SE) to SCIT and treatment compliance at a hospital medically supervised facility. METHODS: A retrospective review of patients with allergic rhino-conjunctivitis (ARC) with or without asthma, who received SCIT to mites and pollens from 1988 to 2018, was performed. The information was collected from patient's allergen immunotherapy forms that had been prospectically filled in by expert physicians. RESULTS: Two thousand two hundred patients (50.2% males; mean age 29.4 ±â€¯11.7 years) received 3037 SCIT courses. A total of 91,187 injections were given, with a mean SCIT duration of 2.5 ±â€¯1.9 years. Nine hundred fifty-seven patients (43.5%) were compliant as they completed the minimally required treatment duration of 3 years. A total of 1087 SE (1.2% of all injections; 76.8% local reactions) were reported in 513 patients (23.3%). There were 42 anaphylactic reactions (in 29 patients) during the study period; two of these were severe. Adrenalin was administered only once. No anaphylactic shock was reported. Only 39 patients (1.8%) discontinued SCIT because of SE, the majority of whom (24; 61.5%) because of systemic reactions (urticaria, asthma, anaphylaxis). Parietaria vaccines were the most frequently associated to SE. Female gender, number of vaccines administered (2 vaccine vs. 1 vaccine) and year of SCIT inception (1996-2018 vs. 1988-1995) were independently associated to SE. CONCLUSION: SCIT, although not absolutely free of risk, is safe and well tolerated. There is still room for improvement of treatment compliance.

Comparison of Six Different Allergen Extracts for Subcutaneous Specific Immunotherapy in Children: An Open-Labelled, Prospective, Controlled Observational Trial.

BACKGROUND: Numerous products are available for subcutaneous (SCIT) and sublingual allergen-specific immunotherapy, but there are no information about the direct comparability regarding efficacy, safety, and tolerability of the different extracts. AIMS: The aim of this open-labelled, prospective, controlled observational trial was to test the feasibility of a comparison of different products for SCIT in children. METHODS: Pediatrician practices recruited patients with a confirmed diagnosis of a seasonal allergic rhinoconjunctivitis (AR) with or without asthma and an allergic sensitization against grass pollen allergen. Every patient was offered SCIT with one out of six allergen extracts: ALK SQ Depot, ALK Avanz, Allergovit, Depigoid, Purethal, Pollinex Quattro. Scores for symptoms and medications were calculated and the difference between treatment years and baseline were recorded. RESULTS: In total, 284 were recruited and 255 children (89.8%; mean age 10.4, SD 3.54 years; 65% males) participated in this trial. Overall, 49,649 patient days were recorded in the electronic database (mean 183.2 days/patient). There was no significant difference in the AR and asthma symptom score or the medication score between the six different SCIT preparations. Similarly, no differences were observed in terms of safety and tolerability. CONCLUSION: The comparison of different SCIT products using an online tool is feasible. Based on our preliminary data, all extracts indicated efficacy; however, larger groups would be necessary to demonstrate superiority or non-inferiority of one specific SCIT product.

The SQ tree SLIT-tablet is highly effective and well tolerated: Results from a randomized, double-blind, placebo-controlled phase III trial.

BACKGROUND: The SQ tree sublingual immunotherapy (SLIT)-tablet (ALK-Abelló, Hørsholm, Denmark) is developed for treatment of tree pollen-induced allergic rhinoconjunctivitis (ARC). OBJECTIVE: The aim of this pivotal phase III trial was to demonstrate the efficacy and safety of the SQ tree SLIT-tablet. METHODS: This was a randomized, double-blind, placebo-controlled trial with 634 subjects (12-65 years) with moderate-to-severe ARC despite use of symptom-relieving medication. Eligible subjects were randomized 1:1 to active or placebo treatment. The primary end point was the average daily ARC total combined score (TCS) during the birch pollen season (BPS) analyzed for subjects with diary data during the BPS. Secondary end points included average daily symptom scores (DSS) during the BPS, average TCS and DSS during the tree pollen season (TPS), and average daily medication scores (DMS) in the BPS and TPS. RESULTS: The primary and key secondary end points demonstrated statistically significant and clinically relevant effects of the SQ tree SLIT-tablet compared with placebo. For the BPS, absolute (relative) differences from placebo were 3.02 (40%) for TCS, 1.32 (37%) for DSS, and 1.58 (49%) for DMS (all P < .0001). For the TPS, absolute (relative) differences from placebo were 2.27 (37%) for TCS, 0.99 (33%) for DSS, and 1.20 (47%) for DMS (all P < .0001). Treatment was well tolerated. The most frequently reported treatment-related adverse events were mild or moderate local reactions related to sublingual administration. CONCLUSION: The trial demonstrated the efficacy and safety of the SQ tree SLIT-tablet compared with placebo during the BPS and TPS in adolescents and adults with birch pollen-induced ARC (EudraCT 2015-004821-15).

Sublingual allergen immunotherapy with a liquid birch pollen product in patients with seasonal allergic rhinoconjunctivitis with or without asthma.

BACKGROUND: Sublingual allergen immunotherapy (SLIT) has been demonstrated to be both clinically efficacious and safe. However, in line with the current regulatory guidance from the European Medicines Agency, allergen immunotherapy (AIT) products must demonstrate their efficacy and safety in pivotal phase III trials for registration. OBJECTIVE: We sought to investigate the efficacy and safety of sublingual high-dose liquid birch pollen extract (40,000 allergy units native [AUN]/mL) in adults with birch pollen allergy. METHODS: A randomized, double-blind, placebo-controlled, parallel-group multicenter trial was conducted in 406 adult patients with moderate-to-severe birch pollen-induced allergic rhinoconjunctivitis with or without mild-to-moderate controlled asthma. Treatment was started 3 to 6 months before the birch pollen season and continued during the season in 40 clinical study centers in 5 European countries. For primary end point assessment, the recommended combined symptom and medication score of the European Academy of Allergy and Clinical Immunology was used. Secondary end points included quality-of-life assessments, immunologic parameters, and safety. RESULTS: Primary efficacy results demonstrated a significant (P < .0001) and clinically relevant (32%) reduction in the combined symptom and medication score compared with placebo after 3 to 6 months of SLIT. Significantly better rhinoconjunctivitis quality-of-life scores (P < .0001) and the patient's own overall assessment of his or her health status, including the visual analog scale score (Euro Quality of Life Visual Analogue Scale; P = .0025), were also demonstrated. In total, a good safety profile of SLIT was observed. CONCLUSION: This study confirmed both the clinical efficacy and safety of a sublingual liquid birch pollen extract in adults with birch pollen allergy in a pivotal phase III trial (EudraCT: 2013-005550-30; ClinicalTrials.gov: NCT02231307).

[Right treatment of red eyes - prescription of topical antibiotics for infectious conjunctivitis is still common in Sweden]. / Rekommendationer följs inte vid okomplicerad konjunktivit - Tillståndet behandlas ofta med topikala antibiotika i strid mot aktuell kunskap.

Conjunctivitis is one of the most common ophthalmologic conditions in general medical practice. In most cases, it is self-limiting and do not require topical antibiotic therapy. In a retrospective, observational cohort study during 2013-2017 in a region in Sweden conjunctivitis was diagnosed in 32 000 cases in primary care. Antibiotics were prescribed in 66% of undefined and in 83% of purulent conjunctivitis. Fusidic acid was the most common medication with 81% followed by chloramphenicol with 17%. Although unnecessary, the treatment is probably harmless. Toxicity is uncommon and the cost is low. Increased consciousness of this issue may however decrease resistance to antibiotics and support evidence-based medical practice.

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.

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.