关于过敏原特异性免疫治疗(AIT)的本指南(S2k)由德国人制定,奥地利和瑞士过敏专业协会与耳鼻咽喉科领域的科学专家协会和专业协会达成共识,皮肤病学和性病学,儿科和青少年医学,肺炎以及德国患者组织(德国过敏和哮喘协会;德国过敏和哮喘,DAAB)根据德国科学医学会协会的标准(ArbeitsgemeinschaftderWissenschaftlichenMedizinischenFachgesellschaften,AWMF)。AIT是一种具有疾病改善作用的疗法。通过施用过敏原提取物,特异性阻断抗体,toler-ance诱导细胞和介质被激活。这些可以防止过敏原触发的免疫反应的进一步恶化,阻断特异性免疫反应并减弱组织中的炎症反应。SCIT或SLIT的产品由于其异质成分目前无法比较,由于测量其活性成分的方法不同,不同制造商给出的过敏原浓度也不能有意义地进行比较。未修饰的过敏原以水性或物理吸附(储库)提取物的形式用于SCIT,以及化学修饰的过敏原(类过敏)作为储库提取物。SLIT的过敏原提取物以水溶液或片剂的形式使用。使用各种评分作为主要和次要研究终点来测量AIT的临床功效。EMA规定综合症状和药物评分为主要终点。临床终点的协调,e.g.,通过使用EAACI推荐的联合症状和药物评分(CSMS),将来是可取的,以便能够比较不同研究的结果。ARIA/GA2LEN小组当前的CONSORT建议规定了评估标准,介绍和发表研究结果。根据治疗过敏原条例(TAV),含有常见过敏原来源的制剂(来自草的花粉,桦木,Alder,Hazel,房子的尘螨,以及蜜蜂和黄蜂毒液)需要在德国的营销授权。在营销授权过程中,这些制剂进行了质量检查,安全性和有效性。在作者看来,授权的过敏原制剂,具有记录的有效性和安全性,或可在TAV下交易的制剂,其功效和安全性已在符合WAO或EMA标准的临床试验中得到证明,应该优先使用。个体配方(NPP)能够处方罕见的过敏原来源(例如,来自灰分的花粉,艾草或安布罗西亚,霉菌,动物过敏原)用于特异性免疫疗法。不允许将这些过敏原与TAV过敏原混合。过敏性鼻炎及其相关的合并症(例如。g.,支气管哮喘)产生大量的直接和间接成本。治疗方案,特别是AIT,因此,使用成本效益和成本效益分析进行评估。从长远来看,在过敏性鼻炎和过敏性哮喘中,AIT被认为比药物治疗更具成本效益,但严重依赖于患者的依从性。荟萃分析为SCIT和SLIT对某些过敏原来源和年龄组的疗效提供了明确的证据。对照研究的数据在范围上有所不同,质量和给药方案,并需要特定产品的评估。因此,建议根据明确定义的标准评估个体制剂.不赞同将某些制剂的功效广泛转移到以相同方式施用的所有制剂。德国变态反应学和临床免疫学学会的网站(www.dgaki.de/leitlinien/s2k-leitlinie-sit;DGAKI:DeutscheGesellschaftfürAllergologieundklinischeImmunologie)providestableswithspecificinformationonavailableproductsforAITinGermany,瑞士和奥地利。这些表格包含每种产品在成人和儿童中的临床研究数量,市场授权之年,底层评分系统,随机和分析的受试者数量和评估方法(ITT,FAS,PP),分别给予草花粉,桦树花粉和屋尘螨过敏原,以及批准使用这些产品进行临床研究的状态。在许多试验中都充分证明了SCIT在成年期花粉过敏引起的过敏性鼻结膜炎中的功效,在童年和青春期,在一些试验中。许多成人对照试验和儿童对照试验证明了屋尘螨过敏的功效。只有几个对照试验,独立于年龄,可用于霉菌过敏(特别是链格孢菌)。关于动物皮屑过敏(主要是猫过敏原),只有一些小的研究,有些方法有缺陷。在迄今为止进行的相当异质性的研究中,仅观察到特应性皮炎的中度和不一致的治疗效果。SCIT已针对全球哮喘倡议(GINA)2007年定义的控制支气管哮喘和间歇性和轻度持续性哮喘(GINA2005)的个体制剂进行了充分的研究,并建议将其作为治疗选择。除了避免过敏原和药物治疗,只要呼吸道症状和相关过敏原之间有明确的因果关系。SLIT在草花粉诱导的过敏性鼻结膜炎中的功效在成人和儿童中得到了广泛的证明,而其在树花粉过敏中的功效仅在成人中显示。关于屋尘螨过敏的新对照试验(一些患者数量较多)提供了SLIT在成人中的有效性的证据。与过敏性鼻结膜炎相比,关于SLIT在过敏性哮喘中的疗效的研究很少.在这种情况下,新的研究表明,SLIT对草花粉过敏儿童亚组哮喘症状的疗效,青少年和成人哮喘患者以及14岁以下青少年和成人对原发性屋尘螨过敏诱发哮喘的疗效。二级预防方面,特别是减少新的致敏剂和降低哮喘风险,是选择在儿童和青春期早期开始治疗的重要理由。在这种情况下,应考虑已证明具有适当效果的产品。使用在至少一项双盲安慰剂对照(DBPC)研究中已证明有效的过敏原提取物,可以在患有过敏性鼻结膜炎的患者中进行带有花粉或螨过敏原的SCIT或SLIT。目前,由于屋尘螨过敏导致的哮喘适应症的临床试验正在进行中,其中一些结果已经发表,而其他人仍在等待中(请参阅DGAKI表“通过www批准/可能完成的研究”。dgaki.de/Leitlinien/s2k-Leitlinie-sit(根据www。临床试验登记。eu)))。当建立AIT指示时,应考虑有利于临床疗效的因素。SCIT和SLIT之间的差异主要考虑禁忌症。在个别情况下,尽管存在禁忌症,但AIT可能是合理的。SCIT注射和SLIT的启动由在这种类型的治疗中经验丰富的医生进行,并且在过敏反应的情况下能够进行紧急治疗。患者必须充分了解程序和可能发生的不良事件的风险。并且必须记录此过程的详细信息(请参阅“治疗信息表”;可通过www作为讲义提供。dgaki.de/Leitlinien/s2k-Leitlinie-sit)。应根据制造商的产品信息手册进行处理。如果AIT将由与确定适应症的医生不同的医生进行或继续进行,需要密切合作,以确保治疗持续实施和低风险。总的来说,建议SCIT和SLIT只能使用可从临床试验中获得足够疗效证明的制剂进行.AIT患者的治疗依从性低于医生的假设,无论管理形式如何。显然,坚持是至关重要的治疗成功。提高AIT依从性是未来最重要的目标之一,以确保治疗的有效性。严重,在SCIT期间可能发生潜在的危及生命的全身反应,但是-只要遵守所有安全措施-这些事件非常罕见。大多数不良事件是轻度至中度的,可以很好地治疗。在SLIT中,口腔和咽喉经常发生剂量依赖性局部不良反应。系统性反应已在SLIT中描述,但与SCIT相比,人们看到的次数要少得多。在过敏反应和其他严重的全身反应方面,SLIT比SCIT具有更好的安全性。通过人员培训,可以有效降低AIT设置中不良全身反应的风险和影响,坚持安全标准,及时采取应急措施,包括早期服用肾上腺素。有关过敏反应的急性管理的详细信息,请参阅AWMF发布的当前S2过敏反应指南(S2-AWMF-LL登记号061-025)。AIT正在许多领域进行一些创新发展(例如g.,过敏原表征,新的管理路线,佐剂,更快、更安全的剂量递增方案),其中一些已经在临床试验中进行了研究。引用这个作为PfaarO,BachertC,BufeA,BuhlR,EbnerC,英语,弗里德里希F,FuchsT,HamelmannE,Hartwig-BadeD,HeringT,HutteggerI,JungK,KlimekL,KoppMV,MerkH,拉贝·U,SalogaJ,Schmid-GrendelmeierP,SchusterA,SchwerkN,SitterH,UmpfenbachU,WediB,WöhrlS,蠕虫M,Kleine-TebbeJ.IgE介导的过敏性疾病中过敏原特异性免疫治疗指南-德国变态反应学和临床免疫学会(DAGAKI)的S2k指南,儿童过敏和环境医学协会(GPA),德国变态反应学家医学协会(AeDA),奥地利过敏和免疫学学会(OGAI),瑞士过敏和免疫学会(SGAI),德国皮肤病学会(DDG),德国耳鼻咽喉科学会,头颈部手术(DGHNO-KHC)德国儿科和青少年医学学会(DGKJ),小儿肺炎学会(3GPP),德国呼吸学会(DGP),德国耳鼻喉科外科医生协会(BV-HNO),儿科医生和青年医生专业联合会(BVKJ),联邦肺病学家协会(BDP)和德国皮肤科医师协会(BVDD)。AllergoJInt2014;23:282-319。
The present
guideline (S2k) on
allergen-specific immunotherapy (AIT) was established by the German, Austrian and Swiss professional associations for allergy in
consensus with the scientific specialist societies and professional associations in the fields of otolaryngology, dermatology and venereology, pediatric and adolescent medicine, pneumology as well as a German patient organization (German Allergy and Asthma Association; Deutscher Allergie- und Asthmabund, DAAB) according to the criteria of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). AIT is a therapy with disease-modifying effects. By administering allergen extracts, specific blocking antibodies, toler-ance-inducing cells and mediators are activated. These prevent further exacerbation of the allergen-triggered immune response, block the specific immune response and attenuate the inflammatory response in tissue. Products for SCIT or SLIT cannot be compared at present due to their heterogeneous composition, nor can allergen concentrations given by different manufacturers be compared meaningfully due to the varying methods used to measure their active ingredients. Non-modified allergens are used for SCIT in the form of aqueous or physically adsorbed (depot) extracts, as well as chemically modified allergens (allergoids) as depot extracts. Allergen extracts for SLIT are used in the form of aqueous solutions or tablets. The clinical efficacy of AIT is measured using various scores as primary and secondary study endpoints. The EMA stipulates combined symptom and medication scores as primary endpoint. A harmonization of clinical endpoints, e. g., by using the combined symptom and medication scores (CSMS) recommended by the EAACI, is desirable in the future in order to permit the comparison of results from different studies. The current CONSORT recommendations from the ARIA/GA2LEN group specify standards for the evaluation, presentation and publication of study results. According to the Therapy
allergen ordinance (TAV), preparations containing common
allergen sources (pollen from grasses, birch, alder, hazel, house dust mites, as well as bee and wasp venom) need a marketing authorization in Germany. During the marketing authorization process, these preparations are examined regarding quality, safety and efficacy. In the opinion of the authors, authorized allergen preparations with documented efficacy and safety, or preparations tradeable under the TAV for which efficacy and safety have already been documented in clinical trials meeting WAO or EMA standards, should be preferentially used. Individual formulations (NPP) enable the prescription of rare allergen sources (e.g., pollen from ash, mugwort or ambrosia, mold Alternaria, animal allergens) for specific immunotherapy. Mixing these allergens with TAV allergens is not permitted. Allergic rhinitis and its associated co-morbidities (e. g., bronchial asthma) generate substantial direct and indirect costs. Treatment options, in particular AIT, are therefore evaluated using cost-benefit and cost-effectiveness analyses. From a long-term perspective, AIT is considered to be significantly more cost effective in allergic rhinitis and allergic asthma than pharmacotherapy, but is heavily dependent on patient compliance. Meta-analyses provide unequivocal evidence of the efficacy of SCIT and SLIT for certain allergen sources and age groups. Data from controlled studies differ in terms of scope, quality and dosing regimens and require product-specific evaluation. Therefore, evaluating individual preparations according to clearly defined criteria is recommended. A broad transfer of the efficacy of certain preparations to all preparations administered in the same way is not endorsed. The website of the German Society for Allergology and Clinical Immunology (www.dgaki.de/leitlinien/s2k-leitlinie-sit; DGAKI: Deutsche Gesellschaft für Allergologie und klinische Immunologie) provides tables with specific information on available products for AIT in Germany, Switzerland and Austria. The tables contain the number of clinical studies per product in adults and children, the year of market authorization, underlying scoring systems, number of randomized and analyzed subjects and the method of evaluation (ITT, FAS, PP), separately given for grass pollen, birch pollen and house dust mite allergens, and the status of approval for the conduct of clinical studies with these products. Strong evidence of the efficacy of SCIT in pollen allergy-induced allergic rhinoconjunctivitis in adulthood is well-documented in numerous trials and, in childhood and adolescence, in a few trials. Efficacy in house dust mite allergy is documented by a number of controlled trials in adults and few controlled trials in children. Only a few controlled trials, independent of age, are available for mold allergy (in particular Alternaria). With regard to animal dander allergies (primarily to cat allergens), only small studies, some with methodological deficiencies are available. Only a moderate and inconsistent therapeutic effect in atopic dermatitis has been observed in the quite heterogeneous studies conducted to date. SCIT has been well investigated for individual preparations in controlled bronchial asthma as defined by the Global Initiative for Asthma (GINA) 2007 and intermittent and mild persistent asthma (GINA 2005) and it is recommended as a treatment option, in addition to allergen avoidance and pharmacotherapy, provided there is a clear causal link between respiratory symptoms and the relevant allergen. The efficacy of SLIT in grass pollen-induced allergic rhinoconjunctivitis is extensively documented in adults and children, whilst its efficacy in tree pollen allergy has only been shown in adults. New controlled trials (some with high patient numbers) on house dust mite allergy provide evidence of efficacy of SLIT in adults. Compared with allergic rhinoconjunctivitis, there are only few studies on the efficacy of SLIT in allergic asthma. In this context, newer studies show an efficacy for SLIT on asthma symptoms in the subgroup of grass pollen allergic children, adolescents and adults with asthma and efficacy in primary house dust mite allergy-induced asthma in adolescents aged from 14 years and in adults. Aspects of secondary prevention, in particular the reduction of new sensitizations and reduced asthma risk, are important rationales for choosing to initiate treatment early in childhood and adolescence. In this context, those products for which the appropriate effects have been demonstrated should be considered. SCIT or SLIT with pollen or mite allergens can be performed in patients with allergic rhinoconjunctivitis using allergen extracts that have been proven to be effective in at least one double-blind placebo-controlled (DBPC) study. At present, clinical trials are underway for the indication in asthma due to house dust mite allergy, some of the results of which have already been published, whilst others are still awaited (see the DGAKI table \"Approved/potentially completed studies\" via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit (according to www.clinicaltrialsregister.eu)). When establishing the indication for AIT, factors that favour clinical efficacy should be taken into consideration. Differences between SCIT and SLIT are to be considered primarily in terms of contraindications. In individual cases, AIT may be justifiably indicated despite the presence of contraindications. SCIT injections and the initiation of SLIT are performed by a physician experienced in this type of treatment and who is able to administer emergency treatment in the case of an allergic reaction. Patients must be fully informed about the procedure and risks of possible adverse events, and the details of this process must be documented (see \"Treatment information sheet\"; available as a handout via www.dgaki.de/Leitlinien/s2k-Leitlinie-sit). Treatment should be performed according to the manufacturer\'s product information leaflet. In cases where AIT is to be performed or continued by a different physician to the one who established the indication, close cooperation is required in order to ensure that treatment is implemented consistently and at low risk. In general, it is recommended that SCIT and SLIT should only be performed using preparations for which adequate proof of efficacy is available from clinical trials. Treatment adherence among AIT patients is lower than assumed by physicians, irrespective of the form of administration. Clearly, adherence is of vital importance for treatment success. Improving AIT adherence is one of the most important future goals, in order to ensure efficacy of the therapy. Severe, potentially life-threatening systemic reactions during SCIT are possible, but - providing all safety measures are adhered to - these events are very rare. Most adverse events are mild to moderate and can be treated well. Dose-dependent adverse local reactions occur frequently in the mouth and throat in SLIT. Systemic reactions have been described in SLIT, but are seen far less often than with SCIT. In terms of anaphylaxis and other severe systemic reactions, SLIT has a better safety profile than SCIT. The risk and effects of adverse systemic reactions in the setting of AIT can be effectively reduced by training of personnel, adhering to safety standards and prompt use of emergency measures, including early administration of i. m. epinephrine. Details on the acute management of anaphylactic reactions can be found in the current S2
guideline on anaphylaxis issued by the AWMF (S2-AWMF-LL Registry Number 061-025). AIT is undergoing some innovative developments in many areas (e. g., allergen characterization, new administration routes, adjuvants, faster and safer dose escalation protocols), some of which are already being investigated in clinical trials. Cite this as Pfaar O, Bachert C, Bufe A, Buhl R, Ebner C, Eng P, Friedrichs F, Fuchs T, Hamelmann E, Hartwig-Bade D, Hering T, Huttegger I, Jung K, Klimek L, Kopp MV, Merk H, Rabe U, Saloga J, Schmid-Grendelmeier P, Schuster A, Schwerk N, Sitter H, Umpfenbach U, Wedi B, Wöhrl S, Worm M, Kleine-Tebbe J.
Guideline on
allergen-specific immunotherapy in IgE-mediated allergic diseases - S2k
Guideline of the German Society for Allergology and Clinical Immunology (DGAKI), the Society for Pediatric Allergy and Environmental Medicine (GPA), the Medical Association of German Allergologists (AeDA), the Austrian Society for Allergy and Immunology (ÖGAI), the Swiss Society for Allergy and Immunology (SGAI), the German Society of Dermatology (DDG), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), the German Society of Pediatrics and Adolescent Medicine (DGKJ), the Society for Pediatric Pneumology (GPP), the German Respiratory Society (DGP), the German Association of ENT Surgeons (BV-HNO), the Professional Federation of Paediatricians and Youth Doctors (BVKJ), the Federal Association of Pulmonologists (BDP) and the German Dermatologists Association (BVDD). Allergo J Int 2014;23:282-319.