Background
Real‐world evidence is sparse on the benefits of allergen immunotherapy AIT; subcutaneous/sublingual immunotherapy (SCIT/SLIT), the only disease‐modifying intervention for allergic ...rhinitis (AR) with long‐term efficacy. This real‐life study evaluated the effect of six AITs (native pollen SLIT/SCIT, four allergoid SCITs) vs symptomatic medication use, on AR symptoms and asthma symptoms/onset, in patients with birch pollen‐associated AR and/or asthma.
Methods
In this retrospective cohort analysis of a German longitudinal prescription database, AIT patients received ≥2 successive seasonal treatment cycles; non‐AIT patients had ≥3 AR prescriptions in three seasons or previous month. Patients were matched for: index year, age, gender, main indication at index, number of seasonal cycles within treatment period, baseline AR/asthma treatment prescriptions. Multiple regression analysis compared prescription data in AIT and non‐AIT groups as proxy for clinical status/disease progression.
Results
Up to 6 years of follow‐up, significantly more AIT (65.4%) vs non‐AIT (47.4%) patients were AR medication‐free; odds ratio (OR) 95% confidence interval (CI): 0.51 (0.48‐0.54); P < 0.001 (28.6% covariate‐adjusted reduction vs non‐AIT; P < 0.001), and significantly more AIT (49.1%) vs non‐AIT (35.1%) patients were asthma medication‐free OR (95% CI): 0.59 (0.55‐0.65); P < 0.001 (32% reduction vs non‐AIT; P < 0.001), or reduced existing asthma medication use (32% covariate‐adjusted reduction vs non‐AIT; P < 0.001). During treatment, new‐onset asthma risk was significantly reduced in the AIT vs non‐AIT group (OR: 0.83; P = 0.001).
Conclusions
Birch pollen AIT demonstrated real‐world benefits up to 6 years post‐treatment cessation through significantly reduced AR and asthma medication intake, and significantly decreased risk of new‐onset asthma medication use on‐treatment.
In this retrospective, real‐world study in Germany, birch pollen allergen immunotherapy (AIT) demonstrated significant benefits up to 6 years post‐treatment in patients with birch pollen‐associated allergic rhinitis (AR) and/or asthma. AIT was associated with significantly improved AR and asthma symptoms as the medication dispensing decreased; nearly two‐thirds and one‐half of patients initially using AR or asthma medications, respectively, no longer required them at study end. During the period in which they were receiving AIT, patients with AR but not asthma had a significantly decreased risk of new‐onset asthma medication dispensing.
Background The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown. Objectives We sought to characterize the evolutionary patterns of ...the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance. Methods We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust. Results One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kUA /L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age. Conclusions Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma.
Background The efficacy and safety of the 300−index of reactivity (IR) dose of 5-grass-pollen sublingual immunotherapy (SLIT) tablets (Stallergènes, Antony, France) have been demonstrated for the ...treatment of hay fever in adults. Objective We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen–related allergic rhinitis. Methods In this multinational, randomized, double-blind, placebo-controlled study, 278 children (5–17 years of age) with grass pollen–related rhinoconjunctivitis (confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement) received once-daily SLIT tablets or placebo. Treatment was initiated 4 months before the estimated pollen season and continued throughout the season. The primary outcome was the rhinoconjunctivitis total symptom score (RTSS), a sum of 6 individual symptom scores: sneezing, runny nose, itchy nose, nasal congestion, watery eyes, and itchy eyes. Secondary end points included rescue medication intake, individual scores, and safety. Results The intent-to-treat population included 266 children (mean age, 10.9 ± 3.22 years). The RTSS for the 300-IR group was highly significantly different from that of the placebo group ( P = .001). The 300-IR group showed a mean improvement for the RTSS of 28.0% over that seen with placebo and a median improvement of 39.3%. Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season ( P = .0064 and P = .0146, respectively). Adverse events were generally mild or moderate in intensity and expected. No serious side effects were reported. Conclusion Five-grass-pollen SLIT tablets (300 IR) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen–related rhinoconjunctivitis.
Background Most infants developing atopic dermatitis have a low risk for atopy. Primary prevention of atopic dermatitis is difficult. Objective To assess the effect of supplementation of an infant ...and follow-on formula with prebiotic and immunoactive oligosaccharides on the occurrence of atopic dermatitis in the first year of life. Methods Healthy term infants from 5 European countries with low atopy risk were recruited before the age of 8 weeks, either having started with formula feeding or being on full breast-feeding (breast-feeding group). Formula-fed infants were randomized to feeding with a regular formula containing a specific mixture of neutral oligosaccharides and pectin-derived acidic oligosaccharides (prebiotic formula group) or regular formula without oligosaccharides (control formula group). Results A total of 414 infants were randomized to the prebiotic group and 416 infants to the control group. A total of 300 infants were followed in the breast-feeding group. Up to the first birthday, atopic dermatitis occurred in significantly fewer infants from the prebiotic group (5.7%) than from the control group (9.7%; P = .04). The cumulative incidence of atopic dermatitis in the prebiotic group was in the low range of the breast-feeding group (7.3%). In a Cox regression model, the rate of atopic dermatitis was significantly lower by 44% in the prebiotic group versus the control group ( P = .04). The number needed to prevent 1 case of atopic dermatitis by supplementation of prebiotics was 25 infants. Conclusion Formula supplementation with a specific mixture of oligosaccharides was effective as primary prevention of atopic dermatitis in low atopy risk infants.
Atopic dermatitis (AD) affects up to 20% of children worldwide and is an increasing public health problem, particularly in developed countries. Although AD in infants and young children can resolve, ...there is a well-recognized increased risk of sequential progression from AD to other atopic diseases, including food allergy (FA), allergic rhinitis, allergic asthma, and allergic rhinoconjunctivitis, a process referred to as the atopic march. The mechanisms underlying the development of AD and subsequent progression to other atopic comorbidities, particularly FA, are incompletely understood and the subject of intense investigation. Other major research objectives are the development of effective strategies to prevent AD and FA, as well as therapeutic interventions to inhibit the atopic march. In 2017, the Division of Allergy, Immunology, and Transplantation of the National Institute of Allergy and Infectious Diseases sponsored a workshop to discuss current understanding and important advances in these research areas and to identify gaps in knowledge and future research directions. International and national experts in the field were joined by representatives from several National Institutes of Health institutes. Summaries of workshop presentations, key conclusions, and recommendations are presented herein.
Background The lack of longitudinal data analyses from birth to adulthood is hampering long-term asthma prevention strategies. Objective We aimed to determine early-life predictors of asthma ...incidence up to age 20 years in a birth cohort study by applying time-to-event analysis. Methods In 1990, the Multicenter Allergy Study included 1314 newborns in 5 German cities. Children were evaluated from birth to age 20 years at 19 time points. Using a Cox regression model, we examined the associations between 36 early-life factors and onset of asthma based on a doctor's diagnosis or asthma medication (primary outcome), typical asthma symptoms, or allergic asthma (including positive IgE measurements). Results Response at 20 years was 71.6%. Two hundred eighteen subjects met the primary outcome criteria within 16,257 person years observed. Asthma incidence was lower in participants who were vaccinated (measles, mumps, and rubella vaccine/tick-borne encephalitis vaccine/BCG vaccine: adjusted hazard ratio HR, 0.66 95% CI, 0.47-0.93). Up to age 20 years, asthma incidence was higher in subjects who had parents with allergic rhinitis (adjusted HR, 2.24 95% CI, 1.67-3.02), started day care early or late (before 18 months: adjusted HR, 1.79 95% CI, 1.03-3.10; after 3 years: adjusted HR, 1.64 95% CI, 0.96-2.79), had mothers who smoked during pregnancy (adjusted HR, 1.79 95% CI, 1.20-2.67), had poor parents (adjusted HR, 1.55 95% CI, 1.09-2.22), and had parents with asthma (adjusted HR, 1.65 95% CI, 1.17-2.31). Not associated with asthma were aspects of diet and breast-feeding, pet ownership, presence of older siblings, and passive smoking. Conclusion Parental asthma and nasal allergy increase asthma incidence in offspring up to adulthood. Avoiding tobacco smoke exposure during pregnancy, receiving vaccinations in early childhood, and starting day care between 1.5 and 3 years of age might prevent or delay the development of asthma.
Background Rhinitis in older children and adults has been shown to be a predictor for adolescent- and adult-onset asthma. These findings suggest an interaction between the upper and lower airways. ...Whether rhinitis is a predictor for childhood-onset asthma is unknown. Objective We sought to investigate whether rhinitis in early childhood is an independent predictor for wheezing between the ages of 5 and 13 years in the German Multicentre Allergy Study birth cohort. Methods The German Multicentre Allergy Study cohort initially included 1314 healthy children. They were followed from birth to the age of 13 years with regular questionnaires and interviews. Specific IgE levels were measured at yearly intervals. Airway hyperresponsiveness was assessed at 7 years. Results Allergic rhinitis until the age of 5 years was found to be a predictor for developing wheezing between the ages of 5 and 13 years, with an adjusted relative risk of 3.82 ( P < .001). This association was not attributable to the type of sensitization, the severity of sensitization, or atopic dermatitis during the first 2 years of life. In this group of children, 41.5% of all new cases of wheezing occurred among children with preceding allergic rhinitis. Conclusions The first manifestation of allergic rhinitis occurs in preschool children in whom it is a predictor for subsequent wheezing onset. Preschool children with rhinitis might thus benefit from early assessment of allergic sensitization to identify the children at high risk of wheezing.
Systemic/oral corticosteroids (OCS) have been used for decades in the management of acute asthma exacerbations and chronically in patients with uncontrolled severe asthma. However, while OCS are ...effective at treating acute exacerbations, there is only empirical evidence regarding the efficacy of OCS at reducing the rate of exacerbations. Evidence, although scarce, is suggestive of high exacerbation rates in severe asthma patients even when receiving maintenance treatment with OCS. In addition, use of OCS is associated with undesirable effects. Despite all this, physicians have continued to use OCS for managing severe asthma and acute exacerbation due to the lack of availability of effective alternatives. Fortunately, in the last decade several biologics have been proven safe and effective for patients with uncontrolled severe asthma. This has led to the Global Initiative for Asthma (GINA) recommending the use of biologics, instead of maintenance OCS, in patients with severe asthma (GINA Step 5). These include one biologic targeting immunoglobulin E (IgE) (omalizumab), and different biologics targeting interleukin-5 (IL-5), the IL-5 receptor (IL-5R) or IL-4 receptor α-unit (IL-4R α), including mepolizumab (subcutaneous), reslizumab (intravenous), benralizumab (subcutaneous) and dupilumab (subcutaneous).
Omalizumab for the treatment of severe allergic asthma reduces exacerbations, irrespective of blood eosinophil levels. Anti-IL-5/IL-5R biologics are indicated in patients with severe eosinophilic asthma and repetitive exacerbations, irrespective of the presence or absence of allergy. Recently, an anti-IL4Rα biologic has been approved by the FDA for eosinophilic phenotype or oral corticosteroid-dependent asthma. Finally, physicians should consider using biologics as an alternative to chronic OCS therapy.
•Oral corticosteroids (OCS) are associated with several adverse effects.•OCS should be prescribed to patients after careful assessments of potential risks compared to benefits.•Omalizumab has 15 years of clinical experience with more than 800,000 patient-years of exposure which make it the first choice of add-on therapy in patients with severe allergic asthma.•Biologics such as omalizumab (anti-immunoglobulin-E) or anti-interleukin (IL), IL-5 and IL-4/IL13, targeting biologics should be considered as alternatives to OCS in patients with uncontrolled severe asthma.•Physicians should either prescribe the appropriate biologic therapy or refer patients with corticosteroid-dependent severe asthma to a specialist.
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