Treatment Of Allergic Rhinoconjunctivitis Research Articles

Assessing serum cytokine and immunoglobulin levels in patients with allergic rhinitis and allergic rhinoconjunctivitis before and after treatment supplemented with macromycetes

Background: In recent decades, the prevalence of allergic rhinitis (AR) has been increasing all over the world including Ukraine. Allergic rhinoconjunctivitis (ARC) is one of the most common clinical forms of AR. An imbalance between pro-inflammatory and anti-inflammatory cytokines is known to have a key role in allergic inflammation. Purpose: To compare cytokine and immunoglobulin levels among patients with AR and ARC treated with different therapeutic options. Material and Methods: Forty patients with AR and ARC (age range, 20 to 46 years) were included in the study. Disease duration ranged from 6 months to 2 years. Patients were divided into two subgroups of 20 patients each. Patients of subgroup 1 received the basic therapy (a 10-mg loratadin tablet daily and mometasone furoate nasal spray at a dosage of 200 μg once daily), whereas patients of subgroup 2, the basic therapy plus polypore macromycetes (Astmagan), one capsule twice daily. Treatment course duration was 90 days. The control group was composed of 25 healthy individuals. A comprehensive clinical immunological examination was conducted at baseline and on the completion of the treatment course. Enzyme-linked immunosorbent assay kits were used to determine serum levels of immunoglobulins A (IgA), IgM, IgG, and IgE, and cytokines (gamma interferon (IFN-γ) and IL4). Results: At baseline, serum levels of IgA, IgM and IgE were almost twice as high (р = 0.0008; 0.0005; and 0.0001, respectively); IgG, 1.2 times higher (р = 0.001); pro-inflammatory cytokine IL4, 3.5 times higher (р = 0.0001); and anti-inflammatory cytokine IFN-γ, 2.4 times lower (р = 0.0001) in patients with AR and ARC compared to controls, and these differences were significant. Astmagan, when used as an adjunct to the basic treatment of AR and ARC, contributed to 8%, 17%, 16.2%, 7.3% and 6.0% greater decreases in the serum levels of IgA, IgM, IgE, IgG and IL4, respectively, and a 16.6% greater increase in the serum level of IFN-γ compared to the basic treatment only, and these differences were significant, with an improvement in immune response to therapy.

A practical guide to prescribing sublingual immunotherapy tablets in North America for pediatric allergic rhinoconjunctivitis: an injection-free allergy immunotherapy option.

Allergic rhinoconjunctivitis (ARC) is a common disease that affects individuals of all ages. Pediatricians may be the first (and only) point of care for children with ARC. Sublingual immunotherapy (SLIT)-tablets are a convenient at-home, injection-free allergy immunotherapy option that can be used for the treatment of ARC. This paper provides a practical guide for pediatricians to aid in prescribing SLIT-tablets to children with ARC in North America. Topics include a summary of the available SLIT-tablets and their efficacy and safety, guidance on when SLIT-tablets are an appropriate option, and how to diagnose ARC and identify culprit allergens. Practical guidance is also provided through a proposed decision tree, a prescribing checklist and prescribing procedures, and suggested follow-up assessments.

Validation and Greenness assessment of UPLC Method for bioanalysis of Bilastine in mice PK study

Bilastine, is a second-generation antihistamine drug which is used in the treatment of allergic rhinoconjunctivitis and urticaria. It exerts its effect as a selective histamine H1 receptor antagonist. In this study, an ultra-high-performance liquid chromatography (UPLC) method was developed to measure the concentrations of Bilastine in mouse blood, and the method was applied in measuring the pharmacokinetics of the analyte after oral and intravenous administration. The analyte was extracted by solid phase extraction method. A UPLC BEH C18 column (2.1 mm × 100 mm, 1.8 ?m particle size) was used for chromatographic separation by gradient elution using acetonitrile-water (0.1% formic acid) as the mobile phase at a flow rate of 0.4 mL/min. Bilastine was administered to the mice orally at 2 mg/kg and intravenously at 0.05 mg/kg. Blood was collected at various time intervals, and the blood samples were processed after collection and analyzed by UPLC. The intra-day and inter-day accuracy of Bilastine were 91%-103% and 85%-107%, respectively, and the precision (RSD, %) was less than 15% for both intra-day and inter-day measurements. The matrix effect ranged from 95% to 108%, and the recovery was higher than 70%. The half-life of bilastine in plasma was found to be 7.02 ± 5.21h. Bilastine has a good linear relationship in the range of 10-500 ng/mL, and the lower limit of quantification was 10 ng/mL. The precision, accuracy, extraction recovery, matrix effect, and stability meet the requirements of the guiding principles. A robust and reliable UPLC method was fully optimized and developed to detect the blood concentration of bilastine in mice and the samples were analyzed by Empower software.

An international Delphi study on the burden of allergic rhinoconjunctivitis and urticaria and the role of bilastine among current treatment options

ABSTRACT Background Allergic rhinoconjunctivitis and chronic urticaria are common histamine-driven diseases, exerting detrimental effects on cognitive functions, sleep, daily activities, and quality of life. Non-sedating second-generation H1-antihistamines are the first-line treatment of choice. Aim of the study was to define the role of bilastine among second-generation H1-antihistamines in the treatment of allergic rhinoconjunctivitis and urticaria in patients of different ages. Methods An international Delphi study was carried out to assess consensus among experts from 17 European and extra-European countries on three main topics: 1) Burden of disease; 2) Current treatment options; 3) Specific characteristics of bilastine among second-generation antihistamines. Results Here, we present the results obtained for a selection of 15 out of 27 consensus statements, focused on disease burden, role of second-generation antihistamines and bilastine profile. The rate of concordance was ≥98% for 4 statements, ≥ 96% for 6, ≥ 94% for 3, and ≥90% for 2. Conclusions The high degree of agreement obtained suggests a wide awareness of the burden of allergic rhinoconjunctivitis and chronic urticaria among experts from all over the world and reflects a broad consensus on the role of second-generation antihistamines in general and of bilastine in particular for their management.

Evaluation of Safety, Efficacy, and Compliance of Intralymphatic Immunotherapy for Allergic Rhinoconjunctivitis: A Systematic Review and Meta-Analysis

Introduction: Intralymphatic immunotherapy (ILIT) is an emerging type of allergen immunotherapy with fewer injections and shorter course for allergic rhinoconjunctivitis (ARC). The efficacy and safety have not been confirmed by informative and powerful evidence yet. Methods: A systematic review and meta-analysis were conducted through electronic searching with PubMed, Web of Science, Embase, Scopus, and China National Knowledge Infrastructure (CNKI). The safety (incidence of adverse events [AEs]), compliance (percent of patients completing treatment), and clinical efficacy of ILIT were evaluated. Clinical efficacy could be assessed by improvement of subjective symptom and rescue medication use or the nasal tolerance to specific allergen. This study is registered with PROSPERO (CRD42022353562). Results: 12 randomized controlled trials (RCTs) comparing ILIT with placebo and 3 trials (2 RCTs and one case-control study) comparing ILIT and SCIT were included in this review. Totally, 582 patients diagnosed as AR or ARC were enrolled. Almost all the AEs were mild-to-moderate reactions except 2 patients developed anaphylactic reactions at the intralymphatic injection dose 5,000 SQ-U in one study. ILIT got higher incidence of local AEs than placebo, but their incidence of systemic AEs was similar. ILIT was safer than SCIT (p < 0.05). Almost all the patients could complete ILIT treatment, and the most common reason for discontinuation of ILIT was AEs. The compliance of patients receiving ILIT seemed higher than patients receiving SCIT. ILIT could significantly ameliorate subjective allergic symptoms, especially for seasonal ARC, and increase nasal tolerance, similar to SCIT. Conclusion: ILIT was a safe and effective treatment for ARC and could achieve comparable clinical improvement with SCIT with shorter duration and higher compliance. Moreover, ILIT was safer than SCIT.

Differences in allergen-specific basophil activation and T cell proliferation in atopic dermatitis patients with comorbid allergic rhinoconjunctivitis treated with a monoclonal anti-IL-4Rα antibody or allergen-specific immunotherapy.

Atopic dermatitis (AD), a chronic inflammatory disorder, is often accompanied by allergic rhinoconjunctivitis (ARC) as a co-morbidity. The use of a monoclonal anti-IL-4Rα antibody has been effective in controlling moderate to severe AD symptoms. Allergen-specific immunotherapy (AIT) is widely used for the treatment of ARC and asthma. The effects of AIT on basophil reactivity/effector functions have already been examined and used as indicators of the treatment efficacy. However, it is unclear, how an anti-IL-4Rα antibody can influence allergen-specific immune responses of basophils and T cells of AD patients with comorbid ARC. To investigate the effect of a monoclonal anti-IL-4Rα antibody on the in vitro allergic responses of basophils and T cells deriving from AD patients with comorbid ARC. Blood samples of 32 AD patients were obtained before, after 4 and 16 weeks of an anti-IL-4Rα antibody therapy (300 mg subcutaneously/2 weeks; n = 21) or AIT (daily sublingual application; n = 11). Patients treated with an anti-IL-4Rα antibody were grouped according to their serum specific immunoglobulin E levels and ARC symptoms, while patients receiving an AIT were additionally grouped according to the allergen specificity of their AIT. Basophil activation test and T cell proliferation assays were undertaken after an in vitro allergen stimulation. A significant reduction of the immunoglobulin E levels and the allergen-specific T cell proliferation was observed in AD patients treated with an anti-IL-4Rα -antibody, while the allergen-specific basophil activation/sensitivity were found to be significantly increased. In patients receiving an AIT, the in vitro allergen-specific basophil activation and the T cell proliferation were found to be significantly decreased in response to seasonal allergens. An IL-4Rα blockade induced by a monoclonal anti-IL-4Rα antibody leads to an increased activity/sensitivity of early effector cells (such as basophils), in contrast to a decreasing reactivity observed under an AIT. The late-phase T cell reaction to allergens did not differ between the herein assessed treatments.

Knowledge mapping of immunotherapy for allergic rhinoconjunctivitis

Allergic rhinoconjunctivitis (ARC) is a common chronic inflammatory disease. Numerous studies on the treatment of ARC have been published. By contrast, there are few bibliometric studies on immunotherapy for ARC. The purpose of this article is to describe the current treatments for ARC and to identify the trends in immunotherapy for ARC. Publications were searched from the Web of Science (WOS) Core Collection on April 25, 2022. CiteSpace and Microsoft Excel software were used for further bibliometric analysis. A total of 969 publications on immunotherapy for ARC in English were retrieved. The number of relevant publications has been continuously increasing over the past 20 years, with many of the publications coming from Germany and the United States of America. In terms of institutions, the ALK Company in Denmark, Imperial College London in United Kingdom, and Charite-Universitatsmedizin Berlin in Germany published the most articles on immunotherapy for ARC. Meanwhile, Allergy and Journal of Allergy and Clinical Immunology published the most number of studies, and Oliver Pfaar from Germany authored the most number of articles. "Subcutaneous immunotherapy," "international consensus," "allergen immunotherapy," and "recommendation" were the most popular subjects. Thus, directions in research can be predicted as studies regarding mechanisms of ARC, clinical trials, and extracts have reported high-quality results. Over the past 20 years, the overall quality of research on immunotherapy for ARC has gradually improved, allowing the introduction of specific and targeted treatment. Currently, the main focus of ARC research is the novel routes of drug delivery and combined treatment with biological agents.

Eosinophilic Esophagitis due to Aeroallergens: A Systematic Review and Update.

Eosinophilic esophagitis is a chronic antigen-mediated esophageal disease characterized clinically by symptoms related to esophageal dysfunction and histologically by TH2 inflammation (at least 15 eosinophils/high power field) when other secondary systemic and local causes of esophageal eosinophilia are excluded. Although this disease was initially ascribed to a delayed reaction to food allergens, emerging evidence suggests that aeroallergens may also play a role in pathogenesis and disease course. Some studies support seasonal variations in the diagnosis of eosinophilic esophagitis and disease exacerbations owing to the increase in aeroallergens to which patients are sensitized. It is also known that this disease can be caused by extensive, identifiable exposure to aeroallergens and after treatment with specific immunotherapy based on food or aeroallergens. It was recently postulated that treatment of allergic rhinoconjunctivitis can improve the symptoms of eosinophilic esophagitis, although data are limited to case reports and small series. Currently, biomarkers and biologic therapies are not helpful for diagnosis or inducing clinical and histological remission of the disease. Nevertheless, there are high hopes for dupilumab. This review aims to give visibility to the involvement of aeroallergens in the triggering and exacerbation of eosinophilic esophagitis, since many of them, in addition to being airborne and inhalant, can also be ingested as food. Clearly, we must try to identify the cause of the disease to ensure remission.

Efficacy and safety of sublingual allergen immunotherapy.

Sublingual immunotherapy (SLIT)-tablets represent a new allergen immunotherapy option for clinicians. In North America, there are five SLIT-tablets approved for the treatment of allergic rhinoconjunctivitis (ARC). No SLIT-drops products are currently approved in the United States or Canada. This work reviewed the efficacy of the timothy grass SLIT-tablet, five-grass SLIT-tablet, ragweed SLIT-tablet, house-dust mite SLIT-tablet, and tree SLIT-tablet in patients with ARC. All the SLIT-tablets showed consistent clinical efficacy for the treatment of ARC in large, double-blind, placebo-controlled trials, including for both patients who were monosensitized and those who were polysensitized. Treatment with house-dust mite SLIT-tablet has shown efficacy in patients who are pollen sensitized during their respective pollen seasons. In contrast to SLIT-tablets, efficacy studies of SLIT-drops show high heterogeneity of treatment effect. Although data are scarce, data that compared the efficacy of SLIT-tablets versus ARC pharmacotherapy generally indicated that SLIT-tablets had a greater benefit than pharmacotherapy when compared with placebo, particularly for perennial ARC. When compared with subcutaneous immunotherapy, analysis of these data indicated that SLIT-tablets had a benefit over subcutaneous immunotherapy in regard to safety but somewhat less benefit in regard to efficacy. The safety of SLIT-tablets has been well documented, and a U.S. Food and Drug Administration class label with safety considerations is present in the prescribing information for all SLIT-tablets. No new safety signals have been observed after reinitiating SLIT-tablets after a short treatment interruption.

Systemic reactions to subcutaneous allergen immunotherapy: real-world cause and effect modelling

BackgroundSubcutaneous immunotherapy (SCIT) is an effective treatment for allergic rhinoconjunctivitis. However, adverse events, including life-threatening systemic reactions, may occur. The purpose of this project is to identify risk factors for systemic reactions to SCIT and to provide practice-based solutions using a quality improvement (QI) framework.MethodsA QI initiative was performed in a hospital-based, Canadian Allergy clinic administering SCIT in a 12-month period.ResultsA total of 4242 injections of SCIT were performed over a period of 12 months. Of these, 10 injections resulted in a systemic reaction requiring epinephrine administration (i.e., an incidence of 1 in 424 injections, or 0.24%). Eight patients had at least one documented risk factor for a systemic reaction, and six had multiple risk factors. Major risk factors included seasonal exacerbation of allergic rhinitis, uncontrolled asthma, and an error in route of administration. All reactions occurred with the highest allergen extract concentration.ConclusionThis QI initiative highlights the need for improved patient and health care practitioner education and pre-administration screening. We suggest several considerations for SCIT administration: provide patients with written information on safety; screen patients before injections, including a review of treatment plan adherence and asthma control; adjust dosing to slow down buildup of the most concentrated immunotherapy extract, particularly in high risk patients; and apply additional safety measures in patients with multiple risk factors.

Comparative analysis of efficacy and safety of Bilastine 20 mg and Levocetirizine 5 mg in the treatment of Allergic Rhinoconjunctivitis

Objective: The present study was conducted to assess the efficacy and safety of bilastine 20 mgand compare the results with that of levocetirizine 5 mg in the treatment of allergicrhinoconjunctivitis. Material and Methods: It was a prospective study conducted in theDepartment of Ophthalmology and Department of Otorhinolaryngology at a tertiary institute ofsouthern Rajasthan, India during the period of 6 months from September 2019 to February 2020.100 patients of chronic allergic rhinoconjunctivitis were included in the study, of which 50 weretreated with Bilastine 20 mg, and the rest 50 patients were treated with levocetirizine 5 mg. Theprimary assessment was done by calculating the total symptom score (TSS) before and after the 7thand 14th post-treatment day. Results: The age of the patients ranges from 10 years to 65 yearswith a mean age of 32±5.2 years. The primary efficacy parameter for assessment was a reduction intotal symptom score (TSS). Both bilastine 20 mg and levocetirizine 5 mg significantly reduced theTSS on the 7th and 14th post-treatment days (p-value&lt; 0.001). There was no significant differencebetween TSS of bilastine and levocetirizine after 7 days (p-value= 0.41) and after 14 days treatment(p-value= 0.68). Adverse events were reported by 10% of patients in the bilastine group and by38% of patients in the levocetirizine group. Conclusion: Bilastine is a selective H1 antihistaminewith good efficacy and excellent safety profile and it is highly recommended to use it as a first-linetreatment for allergic rhinoconjunctivitis.

Complementary treatment of allergic rhinoconjunctivitis: the role of the nutraceutical Lertal(R).

Nutraceuticals represent interesting therapeutic options in clinical practice. In this regard, a new compound has been designed: Lertal®. It contains quercetin, perilla extract, and vitamin D3. These agents exert anti-allergic and anti-inflammatory activities. This article reports and discusses the results of four clinical studies conducted in adult and paediatric patients suffering from AR. Outcomes provided evidence that Lertal® may significantly prevent clinical worsening when prescribed as add-on to continuous antihistaminic treatment and also prevent clinical exacerbations, such as the need of rescue medication, when used alone as preventive strategy in AR patients. (www.actabiomedica.it)

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.

The Efficacy and Safety of Bilastine in the Treatment of Perennial Allergic Rhinitis in Patients with Moderate and Severe Forms of the Disease. Comparison of bilastine 20 mg with desloratadine 5 mg Сергей

Background: Bilastine is a new non-sedating H1 antihistamine approved for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults and children over 12 years of age. In this paper, bilastine was compared with desloratadine in the treatment of various forms of allergic rhino-conjunctivitis classified according to the ARIA recommendations.Materials and Methods: This was an international, multi-centre, open-label, prospective randomized, parallel-group, phase III study which enrolled a total of 226 patients with ARC. The diagnosis of the allergic rhino-conjunctivitis was established on the basis of nasal and non-nasal symptoms and confirmed by the skin prick test. Patients were randomized to one of the two treatment groups: bilastine 20 mg daily or desloratadine 5 mg daily.Results: The results for the primary and secondary endpoints showed a comparable reduction in TSS, NSS, and NNSS from the baseline to the end of the treatment between the treatment groups, with slightly better effects for bilastine. Additional tests carried out in the subgroup of patients with moderate / severe persistent (MSP) ARC demonstrated comparable results for the bilastine and desloratadine groups regarding the mean change in TSS from the baseline until the 28th day, except for the sneezing score, for which bilastine showed the higher response (-1.60 ± 0.60 vs. -1.39 ± 0.63), and a statistically significant difference between the treatment groups regarding AUC for TSS ( -26.07 [95% CI: -48.6, -3.53] p = 0.024), NNSS (-10.51 [95% CI:-19.42, -1.59] p = 0.021), the sneezing score (-4.79 [95% CI:-9.06, -0.51] p = 0.028) and the ocular redness score (-5.50 [95% CI: -8.91, -2.08] p = 0.02).Conclusion: In general, bilastine and desloratadine showed a comparable efficacy profile in the treatment of ARC; however, the results obtained in the subgroup of patients with moderate / severe persistent symptoms indicate that bilastine has a stronger therapeutic effect

Clinical observation of the effect of intranasal corticosteroid plaster in the treatment of allergic rhinoconjunctivitis

Objective To investigate the therapeutic effect of short-term application of intranasal corticosteroid ointment in the treatment of allergic rhinoconjunctivitis (ARC). Methods From December 2016 to December 2017, one hundred and sixty-four patients with ARC were diagnosed in the ophthalmological clinic of the Second Affiliated Hospital of Zhengzhou University, and they were divided into observation group (83 cases) and control group(81 cases) according to the digital table.The observation group was treated with tobramycin dexamethasone ophthalmic ointment, and the control group was treated with azzolastine hydrochloride eye drops.The scores of ocular, nasal symptoms and signs were recorded and compared with before treatment, and the clinical effective rates of the two groups were compared. Results After 14 days of treatment, the scores of nasal symptoms and signs in the two groups were significantly lower than those before treatment(all P<0.05). In the observation group, the scores of nasal symptoms and signs after 14 days of treatment were lower than those in the control group, and the differences were statistically significant (t=3.048, P=0.008; t=3.098, P=0.028). The total effective rates of the observation group and control group were 79.51% and 48.19%, respectively, the difference was statistically significant (χ2=18.644, P<0.05). Conclusion The short-term application of intranasal corticosteroid ointment can effectively relieve the clinical symptoms of ARC.The therapeutics is simple and effective, and it is safe and economical.It is very suitable for wide application and popularization in primary clinical hospitals. Key words: Rhinoconjunctivitis; allergic; Allergic conjunctivitis; Allergic rhinitis; Corticosteroid; H1 antihistamines; Intranasal corticosteroid; Drug therapy; Anti-allergic agents; Ointment

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.

CONJUNCTIVAL PROVOCATION TESTING IN A DOSE FINDING STUDY WITH SUBCUTANEOUS IMMUNOTHERAPY WITH GRASS + MPL

Introduction The total symptom score (TSS) measured during conjunctival provocation testing (CPT) was used as primary endpoint of a Phase II study to evaluate the dose response for a subcutaneous immunotherapy (SCIT) product (1.0 ml) with modified allergen tyrosine adsorbate (MATA) and monophosphoryl lipid A (MPL) adjuvants developed for treatment of allergic rhinoconjunctivitis due to grass pollen [EudraCT 2017-000333-31]. Doses of 5100, 14400, 27600 and 35600 standardized units (SU) and placebo were evaluated. Methods CPTs were performed at screening, pre-dose and approximately 4 weeks post-treatment. TSS was calculated as the sum of 4 symptoms (eye redness, tearing, itching and irritation), each scored on a 4-point scale. Concentrations of 0.3, 1.0, 3.0, 10 and 30 Histamine Equivalent Potency units (HEP)/mL were available for testing. A TSS ≥ 6 points was required at screening and pre-dose. Results The blinded results showed a mean TSS of 7.5 (95% CI: 7.3-7.6) and 4.4 points (95% CI: 4.2-4.7) at pre-dose and post-treatment, respectively. For 251 patients of the 426 patients (58.9%) a positive post-treatment CPT was achieved at least one higher concentration of allergen compared to pre-dose. Conclusions In this Phase II study, CPT was used to establish a dose response of a grass MATA MPL SCIT product using a wide range of cumulative dose regimens. The blinded results indicate adequate CPT performance which may well support the selection of the optimal dose for Phase III, which would be an important milestone in the development of an efficacious and safe pre-seasonal state-of-the-art grass SCIT.

The Role of the Environment in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disease with incompletely understood pathogenesis. Though disease manifestations were initially ascribed to a delayed reaction to food allergens, emerging evidence suggests that modifiable host factors and environmental allergen exposure may also play critical roles in the pathogenesis and ongoing manifestations of EoE. As with other atopic diseases, lack of early-life exposure to microbial pathogens leads to an immune tolerance defect and reprograms the commensal gut microflora toward a type 2 T helper (Th2) phenotype; the esophageal microbiota, a rich environment consisting of diverse bacterial species, is greatly altered by inflammation. Although multiple early life microbiome-altering factors are associated with EoE development, no causative, direct relationships have been identified. Interestingly, large, cross-sectional analyses of several populations identify an inverse relationship between Helicobacter pylori presence and EoE, likely via virulence factors that downregulate Th2 inflammation, though causality has not been proven. In regard to environmental allergens, some studies support seasonal variation in EoE diagnosis and flares, and EoE can be generated after a large, identifiable aeroallergen exposure. Examples include mouse models of intranasal Aspergillus dosing and following initiation of oral immunotherapy to foods or environmental allergens. Conversely, treatment of allergic rhinoconjunctivitis may improve EoE symptoms, though data is limited to case reports and small series. Unfortunately, biologic therapies for atopic conditions have failed to improve EoE symptoms despite improvement in esophageal eosinophil count, though dupilumab shows promise in ongoing studies. Overall, this chapter shows that EoE pathogenesis is likely multifactorial, and the environment is a key component in our understanding of EoE.

Sublingual immunotherapy for pediatric allergic conjunctivitis: a meta-analysis of randomized controlled trials.

Allergic conjunctivitis (AC) is a common chronic condition, especially in children. Ocular symptoms are often overlooked during treatment of allergic rhinoconjunctivitis (ARC). Pediatric ARC can be effectively treated using sublingual immunotherapy (SLIT), which is a guideline-recommended safe treatment approach. However, the therapeutic efficacy of SLIT in terms of ameliorating eye symptoms has not been effectively evaluated. We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the use of SLIT for infants, children, and adolescents (aged from 3 to 18 years) with AC or ARC. We searched the Cochrane Library database, EMBASE, and Medline from November 1990 to 2017 to find papers dealing with the effects of SLIT on pediatric AC or ARC. We used standardized mean differences (SMDs) to assess therapeutic effects, employing a random effects model. Subgroup and sensitivity analyses were also conducted. The I2 metric was used to evaluate heterogeneity. In total, 13 clinical RCTs were included in our meta-analysis. SLIT reduced ocular symptoms to a level below that of controls (SMD = -0.21; 95% confidence interval [CI], -0.41 to -0.01; p = 0.04; I2 = 55%). Notably, on subgroup analysis, SLIT clearly reduced pollen-induced pediatric AC (SMD = -0.36; 95% CI, -0.53 to -0.19; p < 0.0001; I2 = 25%) but not mite-induced AC (SMD = 0.20; 95% CI, -0.20 to 0.60; p = 0.34; I2 = 46%). SLIT relieved ocular symptoms in children with ARC or AC. To confirm these results, future meta-analyses should evaluate high-quality, large-scale population-based trials.

Olopatadine hydrochloride ophthalmic solution for the treatment of allergic conjunctivitis

ABSTRACTIntroduction: Olopatadine hydrochloride is an antihistamine and mast cell stabilizer available as oral, intranasal and ocular preparations. Most of the practical applications of olopatadine therapy focus on the treatment of allergic rhinoconjunctivitis via intranasal and ocular routes.Areas covered: This article was created from a comprehensive literature search with information taken from meta-analyses, systematic reviews, and clinical trials of children and adults. The articles that have been selected, evaluate the use of intranasal and ocular antihistamines and their role in allergic rhinoconjunctivitis.Expert opinion: Olopatadine is significantly more effective than placebos in relieving the symptoms of allergic rhinoconjunctivitis. It can function both as a viable alternative or addition to first line therapies such as intranasal steroids and oral antihistamines.