Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review

Allergen‐specific immunotherapy is one of the cornerstones of allergic rhinoconjunctivitis treatment. Since the development of non‐invasive administration forms with better safety profiles, there is an increasing tendency to prescribe immunotherapy in youngsters. However, no overview is available on the efficacy of immunotherapy in all its different administration forms in youngsters. Therefore, we systematically reviewed randomized controlled trials (RCTs) to evaluate the effect of immunotherapy with inhalant allergens on symptoms and medication use in children and adolescents with allergic rhinoconjunctivitis. Medline, EMBASE, the Cochrane Controlled Clinical Trials Register and reference lists of recent reviews and published trials were searched. RCTs including youngsters aged 0–18 yr with allergic rhinoconjunctivitis and comparing immunotherapy with placebo, symptomatic treatment or a different administration form of immunotherapy were included. Primary outcome measures were rhinoconjunctivitis symptom and/or medication scores. Methodological quality was assessed using the validated Delphi list. A method of best evidence synthesis, a rating system with levels of evidence based on the overall quality and the outcome of the trials, was used to assess efficacy. Six subcutaneous (SCIT), four nasal (LNIT), seven oral (OIT) and 11 sublingual (SLIT) immunotherapy trials, comprising 1619 youngsters, were included. Only 39% of the trials were of high methodological quality. For the SCIT and OIT subgroups the level of evidence for efficacy was conflicting. Moderate evidence of effect was found for LNIT. Analysis of the SLIT subgroup showed no evidence of effect. The evidence for the perennial and seasonal allergen trials within the subgroups varied from moderate evidence of effect to no evidence of effect. In conclusion, there is at present insufficient evidence that immunotherapy in any administration form has a positive effect on symptoms and/or medication use in children and adolescents with allergic rhinoconjunctivitis.     

Spezifische Immuntherapie im Kindesalter

Background

Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy are the two routes for administering allergen-specific immunotherapy for inhalative allergens.

Immunotherapy

The only route of administration for children with bee or wasp venom allergy is SCIT and it is also the primary route of administration for children with asthmatic complaints. Both SCIT and SLIT were shown to be effective in controlling symptoms and in reducing rescue medication in patients with allergic rhinoconjunctivitis sensitized to grass pollens. There is evidence from clinical trials that SLIT with specific grass pollen allergens administered as tablets (e.g. Grazax and Oralair) or drops (Infecto-SLIT forte) is effective and safe in children. A recently published meta-analysis compared both forms of administration and showed a trend toward favoring SCIT for symptom and medication scores. Moreover, local adverse events after SLIT, such as oral pruritus, burning sensation, lip or tongue swelling and gastrointestinal symptoms are pronounced during the first months of administration, which might reduce patient compliance and adherence to specific immunotherapy. Finally, SCIT but not SLIT showed a reduced risk of developing asthma and new sensitization during treatment and 7 years after discontinuation of therapy indicating long-term preventive effects of SCIT.

Conclusions

Although there is evidence of effectiveness of both SCIT and SLIT with grass pollen extracts in patients with allergic rhinoconjunctivitis, SCIT is the primary mode of administration in children. Further research is needed to establish the clinical effectiveness of SCIT versus SLIT in a head-to-head trial in children.     

Hyposensibilisierungstherapie bei allergischen Erkrankungen unter besonderer Berücksichtigung des atopischen Ekzems

According to modern concepts allergen immunotherapy influences the capacity of allergen specific T cells to react to allergen presentation. Subcutaneous immunotherapy with allergen extracts has been shown to be superior to placebo in the treatment of allergic rhinoconjunctivitis and allergic asthma. Because the treatment does not interfere with other antiinflammatory and symptomatic treatments of asthma and rhinoconjunctivitis it is an additional treatment option in children aged 5 years and older in whom allergen exposure is an important determinant of the course of the disease. As yet, there is no sufficient data to recommend allergen immunotherapy in the treatment of atopic eczema. However, allergen immunotherapy for rhinoconjunctivitis or asthma is not contraindicated if atopic eczema is present. If allergy to hymenoptera venom leads to life-threatening symptoms, specific immunotherapy is indicated absolutely even in children below the age of 5 years     

Allergen specific sublingual immunotherapy in children with asthma and allergic rhinitis

Background

The incidence of asthma and allergic rhinitis (AR) is significantly increased, especially in younger children. Current treatment for children with asthma and allergic rhinitis include allergen avoidance, standard pharmacotherapy, and immunotherapy. Since standard pharmacotherapy is prescribed for symptoms, immunotherapy at present plays an important role in the treatment of allergic diseases. This article presents insights into the up-to-date understanding of immunotherapy in the treatment of children with allergic rhinitis and asthma.

Data sources

PubMed articles published from 1990 to 2014 were reviewed using the MeSH terms "asthma", "allergic rhinitis", "children", and "immune therapy". Additional articles were identified by hand searching of the references in the initial search.

Results

Numerous studies have shown that sublingual application of allergen specific immunotherapy (SLIT) is an adequate, safe and efficient substitution to subcutaneous route of allergens administration (SCIT) in the treatment of IgE-mediated respiratory tract allergies in children. According to the literature, better clinical efficacy is connected with the duration of treatment and mono sensitized patients.

Conclusions

At least 3 years of treatment and stable asthma before the immunotherapy are positive predictors of good clinical efficacy and tolerability of SLIT. SLIT reduces the symptoms of allergic diseases and the use of medicaments, and improves the quality of life of children with the diseases.

     

Safety of ultra‐rush titration of sublingual immunotherapy in asthmatic children with tree‐pollen allergy

Mösges R, Graute V, Christ H, Sieber H‐Jochen, Wahn U, Niggemann B. Safety of ultra‐rush titration of sublingual immunotherapy in asthmatic children with tree‐pollen allergy.
Pediatr Allergy Immunol 2010: 21: 1135–1138.
© 2010 John Wiley & Sons A/S The recommendation to use sublingual‐swallow immunotherapy (SLIT) in children and adults with allergic rhinitis has been established over the past decade. Recently, ultra‐rush titration of SLIT has become more and more common, raising concerns about its safety in children with asthma. Fifty‐four children with asthma and adolescents aged 6–14 with documented allergic disease because of tree pollen (birch and possibly alder and/or hazel) from 14 study centers in Germany participated in a randomized, double‐blind, and placebo‐controlled study. Twenty‐seven were randomized to receive SLIT with standardized birch pollen allergen extract and the other 27 to receive placebo. An ultra‐rush high‐dose SLIT titration regimen reaching the maintenance dose of 300 index of reactivity (IR) within 90 min (30–90–150–300 IR) was used. The difference in mean PFR changes during ultra‐rush titration between SLIT and placebo was not significant (p = 0.056). A 95% probability that SLIT does not decrease PFR during ultra‐rush titration was demonstrated. Neither anaphylactic shock nor else serious systemic reactions to the study drug occurred. No serious adverse event assessed by the investigator as related to study drug treatment was reported.     

皮下免疫治疗和舌下免疫治疗对哮喘患儿免疫应答功能影响的比较

目的 比较皮下免疫治疗何舌下免疫治疗对哮喘患儿免疫应答功能影响的差异。方法 收集尘螨致敏哮喘患儿86例,分为舌下免疫治疗组(SLIT组,n=29)、皮下免疫治疗组(SCIT组,n=13)、结束皮下免疫治疗足疗程组(结束SCIT组,n=14)以及常规药物治疗组(对照组,n=30)。体外水平检测各组患儿外周血单个核细胞经螨蛋白浸液刺激后CD4+ T淋巴细胞中调节性T淋巴细胞比例(Treg%)的变化;比较SCIT组和SLIT组患儿治疗前、治疗后6个月、治疗后12个月体液免疫学指标和临床疗效指标变化的差异。结果 未给予抗原刺激时,SCIT组患儿CD4+ T细胞中Treg%显著高于SLIT组、对照组;给予抗原刺激后的4组CD4+ T细胞中Treg%均显著性降低。在免疫治疗后6个月和12个月,SCIT组患儿其血清sIgE和sIgG4水平与治疗前相比差异均有统计学意义,而SLIT组患儿仅血清sIgE水平与治疗前相比差异有统计学意义,sIgG4水平未见随时间变化而变化。结论 不同免疫治疗途径在引发哮喘患儿内在免疫学应答反应上存在时间差异性,其中SCIT免疫治疗患儿免疫应答反应出现的时间更早。     

Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence

Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient’s daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness.     

Two year follow-up of immunological response in mite-allergic children treated with sublingual immunotherapy. Comparison with subcutaneous administration

Although the efficacy of allergen-specific sublingual immunotherapy (SLIT) is now accepted, the underlying mechanisms remain elusive. Such mechanisms are better documented in the case of subcutaneous immunotherapy (SCIT). In order to understand the T-lymphocyte response in patients receiving SLIT, we compared children with respiratory disease monosensitized to Dermatophagoides pteronyssinus receiving SLIT or SCIT over a 2-yr period. Peripheral blood was obtained before beginning immunotherapy, and after 3 months, 1 yr and 2 yr. Total IgE, specific IgE and IgG4 to D. pteronyssinus were determined in serum. T-cell markers (CD3, CD4, CD8, CD25) and intracellular cytokine production (TNF- α , IL-2, IL-4 and IFN- γ ) were determined in peripheral blood mononuclear cells (PBMC) by flow cytometry. No differences between SCIT and SLIT were detected in the clinical variables or in the subjective evaluation. Although an increase in specific IgE and IgG4 was only detected in SCIT, a significant decrease in the specific IgE/IgG4 ratio was found in both groups. SCIT and SLIT experienced an increase in the CD4/CD8 ratio over time, but an increase in the CD4⁺CD25⁺ and a decrease in the CD8⁺CD25⁺ subsets were only found with SCIT. A slight shift from a Th2 to a Th1 pattern, measured by the IFN- γ /IL-4 ratio, was only detected in the CD4 T cells with SCIT. A decrease in both groups was found in TNF- α and IL-2 production over time. Children with respiratory allergic diseases receiving SCIT or SLIT had a different immunologic response in peripheral blood during treatment, though the clinical improvement was similar. Whether SLIT induces a mucosal protective response should be studied.     

尘螨过敏性支气管哮喘的舌下免疫治疗研究进展

在尘螨过敏性哮喘的治疗方法中,螨变应原舌下免疫疗法日益受到关注.其机制尚不十分明确,但可以调节Th1/Th2失衡,促进Th1反应.治疗过程中可降低IgE,升高IgG4,抑制过敏反应的发生.口腔黏膜中的朗格汉斯细胞对提高机体耐受性也发挥着一定的作用.近年来越来越多的研究证明舌下免疫疗法具备有效性、安全性及其良好的依从性....     

随访方式对哮喘儿童舌下含服粉尘螨滴剂依从性的影响

目的评价不同随访方式对哮喘儿童舌下脱敏治疗依从性的影响。方法将112例哮喘(缓解期)合并鼻炎的儿童在接受脱敏治疗后均选择随访,按自愿方式进行分组:69例接受电话随访者为电话随访组,43例不愿接受电话随访者为医院现场随访组。两组患儿在接受脱敏治疗后均告知脱敏常识,纪录联系电话、起始时间、取药时间和数量,每次取药时随访询问效果并纪录;电话随访组加入电话随访,并及时将疗效、不良反应反馈给专科医师。两组均进行为期1年的观察。结果电话随访组坚持1年治疗59例(85.5%),医院随访组坚持1年治疗16例(37.2%)。两组患儿依从性在第6个月、第9个月和12个月,差异都具有统计学意义(χ2=23.71、25.38、27.93,P均<0.001)。随访过程中,未发现舌下脱敏治疗的严重不良事件。结论电话随访方便、快捷,能有效提高患儿舌下脱敏治疗的依从性。     

Eosinophilic gastrointestinal disorders and allergen immunotherapy: Lights and shadows

Allergic diseases, such as IgE-mediated food allergy, asthma, and allergic rhinitis, are relevant health problems worldwide and show an increasing prevalence. Therapies for food allergies are food avoidance and the prompt administration of intramuscular epinephrine in anaphylaxis occurring after accidental exposure. However, allergen immunotherapy (AIT) is being investigated as a new potential tool for treating severe food allergies. Effective oral immunotherapy (OIT) and epicutaneous immunotherapy (EPIT) induce desensitization and restore immune tolerance to the causal allergen. While immediate side effects are well known, the long-term effects of food AIT are still underestimated. In this regard, eosinophilic gastrointestinal disorders (EGIDs), mainly eosinophilic esophagitis, have been reported as putative complications of OIT for food allergy and sublingual immunotherapy (SLIT) for allergic asthma and rhinitis. Fortunately, these complications are usually reversible and the patient recovers after AIT discontinuation. This review summarizes current knowledge on the possible causative link between eosinophilic gastrointestinal disorders and AIT, highlighting recent evidence and controversies.     

儿童过敏性疾病免疫治疗新进展

变应原特异性免疫治疗（AIT）属主动免疫疗法,能调节固有免疫和适应性免疫。变应性鼻结膜炎、哮喘的AIT新途径为淋巴结内免疫治疗和表皮内免疫治疗,但有效性及标准方案仍需进一步研究。低变应原性的重组变应原衍生物和具有免疫原性的肽段,联合新佐剂均是新的AIT研究方向。食物过敏口服免疫治疗具有一定疗效,但不良反应尤其是严重过敏反应的风险仍是需要解决的问题。近年来,被动免疫疗法应用于过敏领域的进展迅速,多种单克隆抗体生物制剂在传统治疗控制不佳的哮喘、特应性皮炎中有着较好效果,AIT联合生物制剂治疗提供了新的治疗选择。     

Efficacy of sublingual specific immunotherapy in intermittent and persistent allergic rhinitis in children: an observational case–control study on 171 patients. The EFESO-children Multicenter Trial

Sublingual‐specific immunotherapy (SLIT) is considered as a valid treatment of respiratory allergies. However, there are few data on large sample size regarding its clinical role in ‘real life’ in term of reduction of symptoms, rescue medications and prevention of asthma in patients suffering from allergic rhinitis (AR) especially in children. We performed a multicenter, case–control study to evaluate the effect of SLIT in children (age 6–18 yr) with intermittent or persistent AR. 171 children (27% girls and 73% boys) with AR due to seasonal or perennial allergens were enrolled in a multicenter case–control study. Cases (n = 90) were defined as patients with intermittent (64%) or persistent (36%) AR who were treated for at least two consecutive years with specific SLIT with the related allergen extracts (SLITone^® ALK‐Abellò). Controls (n = 81) were defined as sex‐age‐ and type of allergen matched AR children who were never treated with specific immunotherapy and had no asthmatic symptoms at the beginning of observation period. Main outcomes of the study were the rhinoconjunctivitis symptom score (SS) (sneezing, rhinorrea, nasal itch, congestion, ocular itch and watery eyes) with a ranging scale from 0 (=no symptoms) to 3 (=severe symptoms) and the medication score (MS) evaluating symptomatic drug intake (antihystamine and inhaled corticosteroids). SS and MS were evaluated at the end of the observational period in relation with the period, considering the last 12 months, in which patients suffered the highest symptoms levels (i.e., peak of relevant pollen season (seasonal AR) or during the period of maximum allergen exposure in case of perennial AR). Secondary outcome of the study was the development of asthma symptoms during the observation period. SS (mean ± SD) was 4.5 ± 2.5 in cases and 9.0 ± 3.0 in controls (?50%) (p = 0.0001). MS (mean ± SD) was 2.5 ± 1.9 and 3.6 ± 2.1 in the case and control groups, respectively (?31%) (p = 0.0001). At the end of the observation period asthma symptoms were present in 14 subjects in the case group (15%) and in 20 children (24%) in the control group (p = 0.13). New skin sensitizations appeared in 6% of cases (n = 2) and in 36% (n = 12) of the controls (p = 0.001). The EFESO trial shows that a 2‐yr once daily SLIT treatment in children with intermittent or persistent AR is associated with lower symptom and medication scores in comparison with subjects treated with symptomatic drugs only.     

Immunotherapy of asthma and allergic diseases

The goals of therapy for allergic disease and asthma, which have increased dramatically during the past 2 decades, are to relieve and prevent symptoms. Currently, allergen immunotherapy is the only available treatment that can reduce symptoms, alter the natural course of disease, and induce long-term clinical remission effectively and safely in patients with allergic rhinitis, asthma, and insect venom anaphylaxis. Allergen immunotherapy may even prevent the evolution towards polysensitization and prevent the development of asthma in allergic children. In the long run, it is more cost-effective than pharmacotherapy and environmental control measures alone. Future developments, such as using alternate routes of administration, peptide fragments of allergen, adjuvants, and DNA vaccines, may improve its efficiency in inducing long-term clinical relief of symptoms.     

标准化尘螨特异性皮下免疫治疗尘螨过敏性哮喘伴变应性鼻炎患儿的长期随访研究

目的：探讨标准化尘螨特异性皮下免疫治疗(SCIT)对尘螨过敏性哮喘伴变应性鼻炎患儿远期疗效的影响。 方法：本文为干预效果的长期随访的病例系列报告。对尘螨过敏性哮喘伴变应性鼻炎患儿,开始接受标准化SCIT治疗（T0）至疗程≥30个月治疗结束（T1）,在T0、T1、T2（T1后的3年）和T3（T1后的6年）,均在哮喘专科门诊或通过电话随访,分别以哮喘症状评分（ASS）、鼻炎症状评分（RSS）、鼻炎与哮喘症状总评分（TSS）、药物评分（TMS）、症状药物总评分（SMS）、视觉模拟量表(VAS)评价和病情改善自我评价量表进行病情估计,ASS、RSS、TSS、TMS评估时点为晚近4周内情况、VAS和病情改善自我评价为患儿或其家长自我感受评估时点为晚近1个月的情况。 结果：2006年4月至2011年6月在哮喘专科门诊诊断为尘螨过敏性哮喘伴变应性鼻炎患儿、且接受了标准化SCIT治疗≥30个月,T1时点56例,男41例,女15例,平均年龄7.1（5~12）岁。均回顾性收集到T0时点病情评估指标ASS、RSS、TSS和VAS,并计算TSS和SMS。随访至T2时点有51例（男38例）和T3时点有45例（男33例）采集到了本文全部病情评估指标。T1时点不同病情评估指标较T0时点差异均有统计学意义。反映病情评估的2个组合指标（TSS和SMS）前后相临时点差异均有统计学意义。病情改善自我评价量表中,变应性鼻炎与哮喘T1时点（18.5% vs 75.0%）、T2时点（31.2% vs 84.0%）、T3时点（39.5% vs 80.0%）比较差异均有统计学意义,病情改善自我评价量表病情评估变应性鼻炎明显差于哮喘。T3时点女生的RSS、TSS、SMS明显低于男生,差异有统计学意义。 结论：标准化SCIT治疗能使尘螨过敏哮喘伴变应性鼻炎患儿的哮喘、鼻炎症状明显减轻,用药减少,VAS评分降低,在停止治疗后的6年仍能维持长期疗效。女性患儿比男性患儿在鼻炎哮喘症状以及症状用药评分方面疗效更加显著。     

Allergen immunotherapy in children

Specific allergen immunotherapy is the only potentially curative allergy treatment currently available. It is used in Europe and North America in the treatment of allergic rhinitis, venom allergy and asthma in children. However, following a series of deaths in the 1980s, the use of immunotherapy in the UK is limited to a small number of specialist allergy clinics. This article reviews the route of administration, safety, efficacy and indications for specific allergen immunotherapy in children. New developments in immunotherapy are discussed.     

舌下特异性免疫治疗对尘螨过敏性哮喘儿童的作用

目的：观察舌下特异性免疫治疗(sublingual immunotherapy, SLIT)联合吸入糖皮质激素(inhaled corticosteroids, ICS)与单独ICS治疗尘螨过敏轻、中度哮喘儿童的临床疗效,为哮喘的联合治疗提供更多的选择方案。方法：对尘螨过敏的轻、中度哮喘患儿32例随机分为两组： SLIT组(SLIT联合ICS治疗,18例)和对照组(单独ICS治疗,14例)。两组共30例完成为期1年的临床观察。比较两组患儿ICS给药总量、哮喘日间和夜间症状评分、皮肤点刺试验、肺功能、血清sIgE和sIgG4值、VAS评分（visual analog scale）的差异。结果：SLIT组在1年治疗结束ICS给药总量较对照组显著减少;与对照组相比,SLIT组的日、夜间哮喘症状评分显著降低,肺功能FEF25- 75%值显著增加,sIgE值及VAS评分降低,差异有统计学意义（P<0.05）;皮肤点刺反应计分、FEV1及sIgG4值两组差异无统计学意义（P>0.05）。在整个随访期两组均无严重不良反应。结论：SLIT联合ICS治疗在改善尘螨致敏哮喘患儿的日、夜间哮喘症状、肺功能及VAS评分方面的疗效优于单独使用ICS治疗。［中国当代儿科杂志,2010,12（5）：344-347］     

Immunomodulation during sublingual therapy in allergic children

The clinical efficacy of sublingual immunotherapy (SLIT) has been demonstrated, but its mechanism of action is still controversial. The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13, by co-stimulatory molecules, such as CD40 on B cells, and by hormones and neuropeptides. To better understand whether SLIT affects immune responses we used a double-blind placebo-controlled design. Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus (33 of whom also had rhinoconjunctivitis) were randomly assigned SLIT (n = 47) or placebo (n = 39). We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP, IL-13, prolactin (PRL) and ACTH at enrolment and after 6 months of therapy. We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group, no variation in CD40 and ACTH, but a significant decrease in ECP, IL-13 and PRL after 6 months of therapy (p <0.01). Our results confirm the efficacy and safety of SLIT, and lead us to believe that it could modulate the synthesis of Th2 cytokines, as revealed from the decrease of IL-13. In addition, the reduction of PRL might be a signal of reduced activation of T lymphocytes.     

Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents

Halken S, Agertoft L, Seidenberg J, Bauer C‐P, Payot F, Martin‐Muñoz MF, Bartkowiak‐Emeryk M, Vereda A, Jean‐Alphonse S, Melac M, Le Gall M, Wahn U. Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents.
Pediatr Allergy Immunol 2010: 21: 970–976.
© 2010 John Wiley & Sons A/S The efficacy and safety of five‐grass pollen 300IR sublingual immunotherapy (SLIT) tablets (Stallergènes SA, France) have previously been demonstrated in paediatric patients. This report presents additional data concerning efficacy at pollen peak, efficacy and safety according to age, nasal and ocular symptoms, use of rescue medication, satisfaction with treatment and compliance. Children (5–11 yr) and adolescents (12–17 yr) with grass pollen–allergic rhinoconjunctivitis were included in a multinational, randomized, double‐blind, placebo‐controlled study and received either a 300IR five‐grass pollen tablet or placebo daily in a pre‐ (4 months) and co‐seasonal protocol. The severity of six symptoms (sneezing, rhinorrhoea, nasal congestion, nasal and ocular pruritis, and tearing) was scored, and rescue medication use was recorded daily during the pollen season. Patient satisfaction was recorded at the season end. A total of 161 children and 117 adolescents were evaluated (n = 267). 300IR SLIT was effective over the whole season (p = 0.0010) and at the pollen peak (p = 0.0009). The adjusted mean difference between 300IR and placebo groups was significant for both nasal (p = 0.0183) and ocular (p < 0.0001) symptoms. Rescue medication use was statistically lower in the SLIT group during the pollen season and at the pollen peak (both p < 0.05). More patients in the SLIT group were satisfied with their treatment compared to placebo (83.2% vs. 68.1%, p = 0.0030), and compliance was high (SLIT 93.9% of patients were compliant, placebo 94.8% of patients were compliant). SLIT was well tolerated by children and adolescents. 300IR five‐grass pollen tablets are effective and safe during the pollen season and at the pollen peak in children and adolescents with grass pollen rhinoconjunctivitis.     

Quantitative assessment of the compliance with once-daily sublingual immunotherapy in children (EASY Project: Evaluation of A novel SLIT formulation during a Year)

Compliance is a major determinant for allergy treatment, especially in children. Sublingual immunotherapy (SLIT) is self-managed at home, and no quantitative data on pediatric adherence are available. We studied the compliance in a large real-life setting. A simplified schedule of SLIT was used, consisting of a 10-day updosing phase followed by maintenance treatment in monodose containers to be taken daily (SLITOne). Italian specialists throughout Italy assessed the compliance in children who were newly prescribed SLIT according to guidelines. Parents were contacted with unscheduled telephone interviews at the third and sixth month of therapy and asked to count at that moment the remaining vials. Data from 71 children (38 boys, age range 2-13 yr) were enclosed in the database. Thirty had rhinoconjunctivitis, four asthma and 37 rhinoconjunctivitis + asthma. SLIT was prescribed for: mites in 57 (81%) subjects, grasses in 11 (15%) and 3 (4%) grass + olive mixture. Compliance data were available for all children at 3 months, and for 56 at 6 months. At 3 months, 85% of subjects had a compliance rate >75% (69% of them adhered >90%). At 6 months, 84% had a compliance rate >75% (66% of them adhered >90%). In four cases SLIT was discontinued for economical reasons, and in one case (1.4%) for side effects probably related to therapy. These data obtained in a quite large sample of children and in real-life confirm that the compliance with SLITOne is good, despite the therapy managed at home.