Supplementary Material for: Rituximab in Subepidermal Blistering Diseases

<b><i>Background:</i></b> Although rituximab is known to be effective in the treatment of pemphigus, its role in subepidermal autoimmune blistering diseases is unclear and currently limited to off-label use. <b><i>Summary:</i></b> This is a meta-analysis of case reports, case series, and retrospective studies on the effectiveness and safety of rituximab in bullous pemphigoid, mucous membrane pemphigoid, ocular pemphigoid, and epidermolysis bullosa acquisita. We compared remission and relapse rates in patients who received rituximab with those who only received conventional medical therapy. Comparisons were also made among disease subgroups. <b><i>Key Message:</i></b> The present analysis suggests that patients with subepidermal autoimmune blistering diseases treated with rituximab achieve a higher rate of complete remission and encounter their first relapse after a longer time interval. However, time to remission and total relapse rates were similar between groups. Adverse events and mortality rates were no more common in patients who received rituximab. This analysis was limited by the absence of randomized controlled trials and the observation that rituximab was used as a late rescue therapy in most reports. In conclusion, rituximab may be effective in subepidermal blistering disease, but randomized controlled studies are required for the validation of current observational data.

**背景**：尽管利妥昔单抗（rituximab）在天疱疮（pemphigus）的治疗中已被证实具有确切疗效，但其在表皮下自身免疫性大疱病（subepidermal autoimmune blistering diseases）中的应用价值仍不明确，目前仅可用于超说明书用药（off-label use）。
**摘要**：本研究针对利妥昔单抗（rituximab）治疗大疱性类天疱疮（bullous pemphigoid）、黏膜类天疱疮（mucous membrane pemphigoid）、眼类天疱疮（ocular pemphigoid）及获得性大疱性表皮松解症（epidermolysis bullosa acquisita）的有效性与安全性，开展了一项涵盖病例报告（case reports）、病例系列（case series）及回顾性研究（retrospective studies）的荟萃分析（meta-analysis）。本研究对比了接受利妥昔单抗治疗与仅接受常规药物治疗（conventional medical therapy）患者的缓解率与复发率，并按疾病亚组进行了分层比较。
**核心结论**：本次荟萃分析结果显示，接受利妥昔单抗治疗的表皮下自身免疫性大疱病患者，其完全缓解（complete remission）率更高，首次复发的时间间隔也更长。但两组患者的达到缓解所需时间（time to remission）及总复发率（total relapse rates）并无显著差异。利妥昔单抗治疗组的不良事件（adverse events）发生率与死亡率（mortality rates）并未高于对照组。本研究存在一定局限性：纳入的原始研究均未设置随机对照试验（randomized controlled trials），且多数报告显示利妥昔单抗被用作晚期挽救治疗（late rescue therapy）手段。综上，利妥昔单抗或可用于表皮下大疱病的治疗，但仍需开展随机对照研究以验证当前的观察性数据（observational data）。