Supplementary Material for: Efficacy of therapeutic apheresis for cryoglobulinemic vasculitis patients with renal involvement: a systematic review

Introduction: Therapeutic apheresis (TA) is commonly used for cryoglobulinemic vasculitis (CV) patients, but its efficacy remains uncertain. This systematic review aimed to assess the efficacy of different TA modalities, such as plasma exchange (PE), plasmapheresis (PP), and cryofiltration (CF), in treating CV patients with renal involvement. Methods: Literature search of MEDLINE, EMBASE and Cochrane Databases was conducted up to December 2022. Studies that reported the outcomes of TA in adult CV patients with renal involvement were assessed. The protocol for this systematic review has been registered with PROSPERO (no. CRD42023417727). The quality of each study was evaluated by the investigators using the validated methodological index for non-randomized studies (minors) quality score. Results: 154 patients who encountered 170 episodes of serious events necessitating TA were evaluated across 76 studies. Among them, 51% were males, with a mean age ranging from 49 to 58 years. The CV types included 15 type I, 97 type II, and 13 type III, while the remaining patients exhibited mixed (n=17) or undetermined CV types (n=12). Among the treatment modalities, PE, PP and CF were performed in 85 (56%), 52 (34%), and 17 patients (11%), respectively, with no identical protocol for TA treatment. The overall response rate for TA was 78%, with response rates of 84%, 77%, and 75% observed in type I, II, and III patients respectively. Most patients received steroids, immunosuppressants, and treatment targeting the underlying causative disease. The overall long-term renal outcome rate was 77%, with type I, II and III patients experiencing response rates of 89%, 76% and 90%, respectively. The renal outcomes in patients receiving PE, PP and CF were comparable, with rates of 78%, 76% and 81%, respectively. Conclusions: This study presents compelling evidence that combination of TA with other treatments, especially immunosuppressive therapy, is a successful strategy for effectively managing severe renal involvement in CV patients. Among the TA modalities studied, including PE, PP, and CF, all demonstrated efficacy, with PE being the most frequently employed approach.

引言：治疗性血液成分单采术（Therapeutic apheresis, TA）是冷球蛋白血症性血管炎（Cryoglobulinemic vasculitis, CV）患者的常用治疗手段，但其临床疗效仍不明确。本系统评价旨在评估不同治疗性血液成分单采术方式——包括血浆置换（Plasma exchange, PE）、血浆分离置换术（Plasmapheresis, PP）及冷滤过术（Cryofiltration, CF）——治疗伴肾脏受累的冷球蛋白血症性血管炎患者的疗效。
方法：检索截至2022年12月的MEDLINE数据库、EMBASE数据库及考克兰（Cochrane）数据库相关文献。纳入报道了伴肾脏受累的成年冷球蛋白血症性血管炎患者接受治疗性血液成分单采术疗效的研究。本系统评价的研究方案已在PROSPERO平台注册（编号：CRD42023417727）。研究人员采用经过验证的非随机研究方法学指数（MINORS）对每项研究的质量进行评分。
结果：共纳入76项研究，涉及154名患者共170次需行治疗性血液成分单采术的严重事件。其中51%为男性，平均年龄区间为49~58岁。冷球蛋白血症性血管炎分型包括I型15例、II型97例、III型13例，其余患者为混合型（n=17）或未明确分型（n=12）。在治疗方式方面，接受PE、PP及CF治疗的患者分别为85例（56%）、52例（34%）及17例（11%），且未采用统一的治疗性血液成分单采术治疗方案。治疗性血液成分单采术的总体应答率为78%，I型、II型及III型患者的应答率分别为84%、77%和75%。多数患者接受了糖皮质激素、免疫抑制剂及针对基础病因的治疗。总体长期肾脏结局良好率为77%，I型、II型及III型患者的肾脏应答率分别为89%、76%和90%。接受PE、PP及CF治疗的患者肾脏结局无显著差异，对应结局良好率分别为78%、76%和81%。
结论：本研究提供了有力证据，表明治疗性血液成分单采术联合其他治疗手段（尤其是免疫抑制剂治疗）可有效管理冷球蛋白血症性血管炎患者的严重肾脏受累情况，是一种成功的治疗策略。在所研究的三种治疗性血液成分单采术方式（PE、PP及CF）中，均展现出治疗有效性，其中PE是最常用的治疗手段。