舌下免疫療法對牧草過敏原過敏具有長期效果

作者：Jacquelyn K. Beals, PhD  
出處：WebMD醫學新聞

　　December 16, 2009（阿根廷布宜諾斯艾利斯）－一項新研究顯示，對抗牧草過敏的舌下免疫療法，在投予期間不但提供症狀緩解，在完成治療療程一年後，仍然可以提供持續的症狀緩解。
　　
　　這項多中心、第三期臨床研究發表在世界過敏組織第21屆世界過敏大會，是一項設計來研究牧草過敏免疫治療錠劑（Grazax，ALK Abello丹麥）用於治療乾草熱的鼻眼結膜特徵的雙盲控制組研究。
　　
　　這項研究收納中重度牧草過敏病患，且對於過去治療結果並不滿意者。一開始的634位參與者被隨機分派接受牧草過敏免疫治療錠劑或是安慰劑，每天一次，共治療三年；第一年的後續追蹤已經完成，而第二年的後續追蹤正在進行中。在第一年結束時，546位參與者仍然在研究中，而351位持續於第二年後續追蹤中。整體來說，這項研究每年退出率約為10%。
　　
　　英國倫敦皇家布朗普頓過敏與呼吸醫學教授、皇家學院國家心臟與肺臟機構部門主任Stephen R. Durham醫師告訴聽眾，退出的病患相較於那些待在研究中的，對於治療的反應基本上是一致的。
　　
　　持續有鼻眼結膜症狀的病患們，在整個牧草季節間，每天一種指標分數評估眼睛與鼻子症狀記錄。該指標評分兩種眼睛症狀與四種鼻子症狀，從0~3分，0分代表沒有症狀，3分代表嚴重症狀。
　　
　　每週以鼻眼結膜炎生活品質問卷（RQLQ）進行評估。在歐洲26個區域取得牧草花粉讀數來評估病患暴露在這些過敏原下的程度。病患被允許使用症狀控制藥物，包括口服或眼滴劑抗組織胺藥物、鼻用類固醇治療、以及口服類固醇，在研究期間視需要使用。只有在牧草季節才每天使用這些藥物。
　　
　　Durham醫師在給Medscape過敏與免疫學的回應中表示，每天治療，持續三年，伴隨而來的是症狀減少30%，暴露在季節性過敏原而需緊急使用抗過敏藥物的需求減少40~50%。
　　
　　在治療後三年，症狀減少仍持續維持下去是最顯著的。Durham醫師表示，這樣的症狀減少持續至少12個月，且在接下來的過敏季節中，仍然維持一樣的好處。這項治療的耐受性良好，不良反應大都與搔癢及嘴巴腫脹有關，大部分在一到兩週內緩解。
　　
　　在第四年結束時，也就是完成牧草過敏錠劑免疫治療後三年，治療組的鼻眼結膜症狀分數低於安慰劑組26%（P<0.001）。治療組使用藥物的分數也低了29%（P<0.02）。RQLQ分數與暴露在牧草過敏原相關，治療組相較於安慰劑組，牧草過敏季節的整體RQLQ分數好了23%（P=0.004）。
　　
　　在發表會上，Durham醫師描述在這麼長的牧草過敏季節中，評估鼻眼結膜分數是項挑戰，這些日子裡，至少有40%的時間，空氣都有些許的過敏原。他的統計人員將這些日子以每10天進行區分，並計算累計整體過敏原數量。當過敏原數量低於10的那些日子，大約有70%病患是沒有症狀的，25%有輕中度症狀，而僅5%病患有嚴重症狀。當過敏原計數高時，更多病患有更嚴重的症狀。
　　
　　合併症狀與藥物分數及過敏原計數的圖表顯示治療組與安慰劑組之間清楚地分開。有趣的是，兩組間的差異在研究的第三年和第四年最為明顯。除此之外，治療組與安慰劑組的差異隨著過敏原計數增加而更為顯著。
　　
　　Durham醫師向Medscape過敏與免疫學表示，過敏原免疫治療對於罹患嚴重乾草熱的病患來說是有效的。這是第一次，我們提供以舌下投予牧草錠劑免疫療法有持續效果的可信證據。
　　
　　座談會共同引言人、丹麥哥本哈根過敏學習與諮詢主任Lars Jacobsen碩士進一步解釋舌下免疫療法的優點，他指出，其優點在於，用於舌下免疫療法的藥物需有很好的安全性才能在家治療，他向Medscape過敏與免疫學表示，靜脈注射必須要由合格的醫師執行，以避免副作用的潛在風險。
　　
　　Jacobsen先生表示，就如同我們所看到的，看起來我們可以達到同樣的臨床效果（以舌下投予免疫治療相較於皮下注射免疫治療）。因此，舌下投予（免疫療法）的好處是你可以在家進行治療，壞處是你必須每天吃藥，但如果是注射的，你只要每八個星期找一次醫師注射藥物就可以了。
　　
　　Jacobsen先生表示，以皮下投予免疫療法已經證實有長期效果。這是我們首次證實舌下似乎與皮下注射免疫療法有一樣的長期好處。
　　
　　Durham醫師表示接受ALK Abello公司研究經費、演講與擔任顧問費用，該公司過敏疫苗的製造商。Jacobsen先生表示他是SQ錠劑計畫的共同設計者。


Sublingual Immunotherapy for Grass Pollen Allergy Has Long-Lasting Effect

By Jacquelyn K. Beals, PhD
Medscape Medical News

December 16, 2009 (Buenos Aires, Argentina) — A new study shows that sublingual immunotherapy against grass pollen allergy not only provides symptom relief during the period of administration, it also has long-lasting effects on symptom reduction 1 year after completing the course of treatment.

The multinational phase?3 trial, presented here at the World Allergy Organization XXI World Allergy Congress, was a double-blind placebo-controlled trial designed to investigate the effect of grass allergen immunotherapy tablets (Grazax, ALK Abello, Denmark) in treating rhinoconjunctivitis characteristic of hay fever.

The study enrolled patients with moderate to severe grass pollen allergy who were dissatisfied with their previous treatment results. The initial 634 participants were randomly assigned to receive either grass allergy tablet immunotherapy or a placebo once a day for 3 years; 1 year of follow-up has been completed and a second year is ongoing. At the end of the first year, 546 patients were still participating and 351 have continued into the second year. Overall, the study has seen about a 10% drop-out rate each year.

"Patients who dropped out were compared with those who stayed in, and their response to treatment was nearly identical," said Stephen R. Durham, MD, FRCP, head of the section for allergy and clinical immunology at the National Heart and Lung Institute, Imperial College, and professor of allergy and respiratory medicine at Royal Brompton Hospital, in London, United Kingdom, to the audience. "So we're not looking at a responder population."

Patients kept rhinoconjunctivitis symptom records on eye and nose symptoms, with a scoring scale assessed daily during the entire grass pollen season. The scale rates 2 eye symptoms and 4 nasal symptoms on a scale from 0 to 3, with 0 representing absence of symptoms and 3 representing severe symptoms.

A Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) was completed weekly. Grass pollen counts were obtained from 26 sites in Europe to estimate patients' exposure to the grass pollen allergen. Patients were allowed to take symptomatic medications, including oral or eye-drop antihistamines, nasal steroid spray, and oral steroids, as needed throughout the study. Medication use was noted daily throughout the grass pollen season.

"Daily treatment over 3 years was accompanied by an approximate 30% reduction in symptoms and a 40% to 50% reduction in rescue antiallergic drugs during seasonal pollen exposure," Dr. Durham said in correspondence with Medscape Allergy and Immunology.

Of great significance was the persistence of symptom reduction following the 3-year treatment. This reduction "persisted for at least 12 months, with the same benefit during the following season," Dr. Durham noted. "The treatment was well tolerated, with side effects largely confined to itching and swelling in the mouth that resolved within 1 to 2 weeks."

At the end of the fourth year — a year after completing 3 years of grass allergy tablet immunotherapy — rhinoconjunctivitis scores in the treated group were 26% lower than those in the placebo group (P?< .001). Medication scores were 29% lower in the treatment group (P?< .02). The RQLQ scores correlated with exposure to grass pollen, and the overall RQLQ score for the grass pollen season was 23% better (a lower score) in the treatment group than in the placebo group (P?= .004).

During his presentation, Dr. Durham described the challenges of assessing rhinoconjunctivitis scores during a long pollen season in which, at least 40% of the days, little pollen was in the air. His statistician clumped the days into groups of 10, with cumulative total pollen counts. On days when pollen counts were below 10, approximately 70% of patients were asymptomatic, 25% had moderate to mild symptoms, and only 5% had severe symptoms. When pollen counts were high, many more patients showed severe symptoms.

Plotting a combined symptom and medication score against pollen counts showed a clear separation between the treatment and placebo groups. Interestingly, the difference between groups was larger during the third and fourth year of the study. In addition, the difference between the treated and placebo groups became more marked as pollen counts increased.

"Allergen immunotherapy is effective in patients with severe hay fever," Dr. Durham told Medscape Allergy and Immunology. "For the first time, we provide convincing evidence that grass tablet immunotherapy via the sublingual route results in a long-lasting effect."

The advantages of sublingual immunotherapy were further explained by session comoderator Lars Jacobsen, MSc, director of Allergy Learning and Consulting in Copenhagen, Denmark. "The advantage of the sublingual immunotherapy is that?.?.?. the drug that is used for sublingual immunotherapy carries a safety profile that allows for home treatment.?.?.?. Injection therapy has to be performed by a qualified doctor in order to avoid potential risk of side effects," he told Medscape Allergy and Immunology.

"As we see now,?.?.?. it seems that we can achieve the same clinical effect [with sublingual immunotherapy as with subcutaneous immunotherapy]. So the advantage of sublingual [immunotherapy] is that you can use it as a home treatment," said Mr. Jacobsen. "The disadvantage is that you [have to take] the drug every day, whereas with the shots, you [only have to get] to the doctor every 8 weeks to get the injection."

"It has been shown, with subcutaneous immunotherapy, that there's a long-term effect," noted Mr. Jacobsen. "This is the first time that we can show that sublingual immunotherapy seems to carry the same benefit as injected immunotherapy in the long term."

Dr. Durham reports receiving research funding and lecture and consultancy fees from ALK Abello, a manufacturer of allergy vaccines. Mr. Jacobsen reports that he was a codesigner on the SQ tablet project.

World Allergy Organization XXI World Allergy Congress (WAC): Abstract?914. Presented December?9, 2009.