- 學位論文
使用莫須瘤在天疱瘡治療之有效性與安全性-系統性文獻回顧與統合分析
A systematic review and meta-analysis on the efficacy and safety of rituximab in the treatment of pemphigus
摘要
天疱瘡是一種罕見的自體免疫疾病，好發於中年人。其主要特點會在皮膚或黏膜上出現水疱、疼痛的破皮傷口，甚至皮膚糜爛。天疱瘡主要是因為患者體內產生了對抗表皮的自體免疫抗體，而攻擊原本正常的表皮，特別是細胞膜表面的蛋白desmoglein 1 (Dsg 1) 與desmoglein 3 (Dsg 3)而導致表皮細胞鬆解。臨床上可以觀察到很多因反覆性口腔潰瘍、長時間無法治癒而到皮膚科求診的案例，患者也可以合併有皮膚淺層的水疱與潰瘍。病理切片下會看到棘狀層分解形成的表皮內水疱，免疫螢光染色下則可見到表皮細胞間呈現網狀排列之免疫球蛋白沉積。 天疱瘡目前的主流治療方式是使用高劑量的類固醇。這是最常使用，療效也最快的治療方式；近年來，抗CD20 抗體生物製劑「莫須瘤(rituximab)」則成為新的治療方式。它是一種單株抗體，首先在1997 年於美國核准用於治療淋巴癌，它在B 淋巴細胞上與CD20 抗原結合後促使B 細胞溶解，可以有效除去淋巴球中的B 細胞，因此可用於治療自體免疫疾病。多篇研究指出「莫須瘤(rituximab)」可以有效治療天疱瘡，美國食品藥物管理局(FDA)亦於2018 年6月7 日核准該藥使用於尋常型天疱瘡之適應症，惟最佳劑量尚未有隨機分配之臨床試驗證實，故筆者以系統性文獻回顧與統合分析探討現有臨床數據後，設計一隨機分派、開放性臨床試驗，用以確定不同劑量模式之「莫須瘤(rituximab)」使用於天疱瘡病人的療效性與安全性。
並列摘要
Pemphigus is a rare, yet life-threatening disease. It is characterized by erosions andblisters on the skin and mucous membranes. The disease often occurs in middle agedpeople. The surface of keratinocytes is targeted by autoantibodies against antigens onthe skin. Two main desmogleins are associated with this autoimmune intraepithelialblistering skin disease, desmoglein 1 and desmoglein 3. The antibody directed against epidermal adhesion complexes (desmosomes) leads to loss of cell cell adhesion, a phenomenon called acantholysis. Some patients suffer from oral ulcers at first, then blisters which are flaccid and are easily broken, leading to often-painful lesions or erosions on the skin. Direct immunofluorescence(DIF) examination may show the presence of intercellular deposition ofimmunoglobulins. Systemic corticosteroids have been the mainstay of pemphigus therapy for many years. An anti-CD 20 antibody, rituximab, acts by depleting B cells, has shown efficacy in patients with pemphigus subjects. It has also been approved by the U.S. Food and Drug Administration (FDA) in 2018 for the treatment of pemphigus vulgaris, although the best dose regimen has not been verified. Hence, we conducted this meta analysis on the efficacy and safety of rituximab in the treatment of pemphigus, and also established a randomized, open-labeled study protocol to determine the best dosing regimen of rituximab for treatment of pemphigus.