Hagen Anja, Gorenoi Vitali, Schönermark Matthias P
Institute for Epidemiology, Public Medicine and Healthcare Systems Research, Hannover Medical School, Hannover, Germany.
GMS Health Technol Assess. 2010 Mar 16;6:Doc01. doi: 10.3205/hta000079.
Allergic rhinitis (AR) exhibits a prevalence of approx. 20% in Germany and causes enormous costs in the health care system. Specific immunotherapy (SIT) is considered to be the only potentially causal therapy for AR and mainly administered by two routes, subcutaneous (SCIT) and sublinguale (SLIT). SIT promises a reduction of symptoms and the need for medication in patients with AR.
The question arises, to what extent is SIT effective and cost effective in the treatment of AR and which ethical-social and legal aspects have to be considered regarding its application.
The literature search was accomplished in the electronic data bases MEDLINE, EMBASE etc. in February 2008. The medical evaluation was based on systematic reviews of blinded, randomised controlled studies (RCT). The economic evaluation included health-economic studies on the basis of RCT. Additionally, it was also searched for publications explicitly addressing ethical-social and legal aspects of the use of SIT.
MEDICAL EVALUATION: Two reviews on SCIT and three on SLIT were included in the medical evaluation. For the evaluation of SIT with grass pollen results for short and medium-term effects are considered from several studies, for SIT with other seasonal allergens (e. g. tree pollen) and with house dust mite allergens from clearly fewer studies and for SIT with other perennial allergens only from a few. The reviews report a significant reduction of the symptom and medication score in favour of SCIT with seasonal allergens and recognise the effectiveness at least for grass pollen allergens. Also for other seasonal allergens SCIT is appraised as effective. The reviews about SLIT determine a significant reduction of the symptom and the medication score in favour of SLIT vs. placebo in short and medium term follow-up in evaluations across all allergens. The subgroup analyses show a significant reduction of the symptom and medication score only in favour of SLIT with seasonal allergens. HEALTH ECONOMIC EVALUATION: Four publications about two health economic studies are identified, one of these publications on Alutard-SQ(®) injections (SCIT) and three on GRAZAX(®) tablets (SLIT). The studies provide more (on Alutard-SQ(®)) or less (on GRAZAX(®)) robust information, but no evidence on cost effectiveness of these SIT administration forms in patients with AR.
The topic of the report is very broad, so that the evidence is summarised using systematic reviews. In particular the statistic heterogeneity of the studies found in the reviews considerably limits the strength of the findings. The included health economic studies show different methodical flaws, the largest potential bias is the projection of the magnitude of the medium-term clinical effects on the time period of nine years.
The effectiveness of SIT in patients with AR is not equally proven for all SIT administration forms and allergens. For SCIT and SLIT with grass pollen allergens short and medium-term effectiveness can be regarded as proven. These therapy forms should be used if the indication is appropriate and if no contraindications are present. Also SCIT and SLIT with other seasonal allergens such as tree pollen allergens can be an effective treatment option, but used with a certain restraint due to insufficient data especially in the case of SLIT. For SIT with house dust mite allergens and further perennial allergens no consistent proof of effectiveness are to be determined from the available information. Further research addressing non-grass pollen-associated SIT, allergen and manufacturer specific evaluations as well as asthma prevention is needed. Due to the lack of evidence the use of SIT can not be seen proven as cost effective. To provide such evidence further health economic studies with a long term follow-up are needed. The informed consent of the patients is an important ethical requirement within the use of SIT.
变应性鼻炎（AR）在德国的患病率约为20%，给医疗保健系统带来了巨大成本。特异性免疫疗法（SIT）被认为是AR唯一可能的病因疗法，主要通过皮下（SCIT）和舌下（SLIT）两种途径给药。SIT有望减轻AR患者的症状并减少用药需求。
SIT在治疗AR方面的有效性和成本效益如何，以及在其应用中必须考虑哪些伦理 - 社会和法律方面的问题。
2008年2月在电子数据库MEDLINE、EMBASE等中进行文献检索。医学评估基于对盲法随机对照研究（RCT）的系统评价。经济评估包括基于RCT的卫生经济学研究。此外，还搜索了明确涉及SIT使用的伦理 - 社会和法律方面的出版物。
医学评估：医学评估纳入了两项关于SCIT的综述和三项关于SLIT的综述。对于草花粉SIT的评估，多项研究考虑了短期和中期效果；对于其他季节性变应原（如树花粉）和屋尘螨变应原的SIT，研究较少；对于其他常年性变应原的SIT，仅有少数研究。综述报告称，季节性变应原的SCIT使症状和用药评分显著降低，且至少对草花粉变应原有效。对于其他季节性变应原，SCIT也被评估为有效。关于SLIT的综述表明，在所有变应原的评估中，短期和中期随访时，与安慰剂相比，SLIT使症状和用药评分显著降低。亚组分析显示，仅季节性变应原的SLIT使症状和用药评分显著降低。卫生经济评估：确定了关于两项卫生经济学研究的四篇出版物，其中一篇关于Alutard - SQ（®）注射剂（SCIT），三篇关于GRAZAX（®）片剂（SLIT）。这些研究提供了或多或少可靠的信息，但没有关于这些SIT给药形式对AR患者成本效益的证据。
报告主题非常广泛，因此使用系统评价来总结证据。特别是综述中发现的研究的统计异质性极大地限制了研究结果的强度。纳入的卫生经济学研究存在不同的方法学缺陷，最大的潜在偏差是将中期临床效果的程度推算到九年的时间段。
并非所有SIT给药形式和变应原在AR患者中的有效性都得到了同等程度的证实。对于草花粉变应原的SCIT和SLIT，短期和中期有效性可视为已得到证实。如果适应证合适且无禁忌证，应使用这些治疗形式。对于其他季节性变应原如树花粉变应原的SCIT和SLIT也可以是一种有效的治疗选择，但由于数据不足，尤其是SLIT的情况，应谨慎使用。对于屋尘螨变应原和其他常年性变应原的SIT，从现有信息中无法确定一致的有效性证据。需要进一步开展针对非草花粉相关SIT、变应原和制造商特定评估以及哮喘预防的研究。由于缺乏证据，SIT的使用不能被视为具有成本效益。为提供此类证据，需要进一步进行长期随访的卫生经济学研究。患者的知情同意是SIT使用中的一项重要伦理要求。
