BUCM循證醫學精視角 - 【Cochrane簡語概要】預防遺傳性血管性水腫發作的藥物治療－鑽石舞台

什麼是遺傳性血管性水腫以及如何治療？

遺傳性血管性水腫（Hereditary angioedema, HAE）是一種嚴重且可能危及生命的疾病，會導致急性腫脹（突然發作）、疼痛和生活質量下降。現已有幾種新藥被用來治療HAE急性發作和防止其復發。有些藥物是口服的，而另一些則是皮下注射，或通過靜脈直接注入血液。

目前用於預防HAE發作的藥物是人C1酯酶抑制劑（通常縮寫為C1-INH）、貝羅司他、拉那蘆人單抗、氨甲環酸和達那唑。此外，我們還發現了另一種藥物（阿伏司他），其預防HAE發作的能力正在研究當中。

（圖片來自scarysymptoms.com）

我們想知道什麼？

我們調查了這些藥物是否會減少HAE發作的次數，以及如果發作，那麼發作的嚴重程度是否比不用藥物時低。我們還研究了服用這些藥物的人是否有更好的生活質量，以及這些藥物是否會引起不必要的副作用。

我們做了什麼？

我們在醫學數據庫中檢索了針對患有HAE的兒童或成人的臨床研究，這些研究將預防HAE發作的藥物與安慰劑（一種假治療）或其他藥物進行了比較。

我們發現了什麼？

我們找到了15項研究，共有912名受試者。除阿伏司他外的所有藥物都減少了HAE發作的次數，即使確實發作了，使用了C1-INH和拉那蘆人單抗的患者嚴重程度也較低（沒有關於其他藥物的結果）。我們發現大多數藥物改善了HAE患者的生活質量，並且通常是安全的，因為它們不會增加嚴重和不太嚴重的副作用的數量。

尚無研究測試了氨甲環酸，只有一項研究測試了達那唑。尚無研究直接將一種藥物與另一種藥物進行比較。這意味着我們不能肯定地說一種藥物是否比另一種更好。

結論

C1-INH、貝羅司他、拉那蘆人單抗和達那唑似乎可以降低HAE發作的風險並提高HAE患者的生活質量。這些藥物似乎不會導致副作用增加。

證據的局限性有哪些？

我們研究結果的局限性在於研究數量少和每項研究受試者人數少。因此，我們對這些結果的可信度為低。

證據的時效性如何？

證據截止至2021年8月3日。

作者結論:

現有數據表明，貝羅司他、C1-INH（皮下、血漿衍生、納米過濾和重組）、達那唑和拉那蘆人單抗可有效降低HAE發作的風險或發生率（或兩者兼而有之）。此外，C1-INH和拉那蘆人單抗降低了突破性發作的嚴重程度（其他藥物的數據不可用）。阿伏司他、貝羅司他、C1-INH（所有形式）和拉那蘆人單抗可提高生活質量，並且不會增加不良事件的風險，包括嚴重的不良事件。達那唑、皮下C1-INH和重組人C1-INH在降低突破性發作風險方面可能比貝羅司他和拉那蘆人單抗更有效，但研究數量少和研究規模小意味着證據質量等級為低。這種情況以及缺乏頭對頭試驗使我們無法就藥物的相對療效得出確切的結論。

作者:Beard N, Frese M, Smertina E, Mere P, Katelaris C, Mills K；譯者：黃澤浩，Cochrane Hong Kong，香港中文大學醫學院那打素護理學院；審校：牟煥玉，Cochrane Hong Kong，香港中文大學醫學院那打素護理學院；編輯排版：索于思，北京中醫藥大學循證醫學中心

【Cochrane Plain Language Summary】

Drug treatments for the prevention of attacks of hereditary angioedema

What is hereditary angioedema and how is it treated?

Hereditary angioedema (HAE) is a serious and potentially life-threatening condition that causes acute (sudden onset) attacks of swelling, pain and reduced quality of life. Several new medicines have been developed to treat acute attacks and prevent attacks from occurring. Some medicines are taken by mouth, whereas others are injected under the skin, or given by a vein directly into the blood.

The medicines currently given for preventing HAE attacks are human C1 esterase inhibitor (often abbreviated as C1-INH), berotralstat, lanadelumab, tranexamic acid, and danazol. In addition, we found a further medicine (avoralstat) that is currently being studied for its ability to prevent HAE attacks.

What did we want to find out?

We investigated whether these medicines reduce the number of HAE attacks, and if any attacks that do occur are less severe than they would otherwise be. We also looked at whether people taking the medicines experienced a better quality of life, and whether the medicines caused unwanted side effects.

What did we do?

We searched medical databases for clinical studies in children or adults with HAE that compared medications to prevent HAE attacks with placebo (a pretend treatment) or another medicine.

What did we find?

We found 15 studies with 912 participants. All medicines except avoralstat reduced the number of HAE attacks, and even when attacks did occur, they were less severe for C1-INH and lanadelumab (there were no results for the other medicines). We found that most medicines improved the quality of life of the people with HAE and were generally safe as they did not increase the number of serious and less serious side effects.

We found no studies that tested tranexamic acid, and only one study tested danazol. There were also no studies that compared one medicine directly with another. This means that we cannot say for sure whether one medicine is better than another.

Conclusions

C1-INH, berotralstat, lanadelumab and danazol appear to reduce the risk of HAE attacks and increase the quality of life in people with HAE. The medicines do not seem to result in an increase in side effects.

What are the limitations of the evidence?

Our findings are limited by the small number of studies and the small number of participants in each study. Therefore, our confidence in these findings is low.

How up to date is this evidence?

The evidence is current to 3 August 2021.

Authors' conclusions:

The available data suggest that berotralstat, C1-INH (subcutaneous, plasma-derived, nanofiltered and recombinant), danazol and lanadelumab are effective in lowering the risk or incidence (or both) of HAE attacks. In addition, C1-INH and lanadelumab decrease the severity of breakthrough attacks (data for other drugs were not available). Avoralstat, berotralstat, C1-INH (all forms) and lanadelumab increase quality of life and do not increase the risk of adverse events, including serious adverse events. It is possible that danazol, subcutaneous C1-INH and recombinant human C1-INH are more effective than berotralstat and lanadelumab in reducing the risk of breakthrough attacks, but the small number of studies and the small size of the studies means that the certainty of the evidence is low. This and the lack of head-to-head trials prevented us from drawing firm conclusions on the relative efficacy of the drugs.