CMID-Nephrology and Dialysis Unit, Center of Research of Rheumatologic, Nephrologic and Rare Diseases, and Coordinating Centre of the Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hospital and University of Turin, Italy.
Clin Exp Rheumatol. 2020 Mar-Apr;38 Suppl 124(2):195-200. Epub 2020 May 22.
Immunoglobulin-A vasculitis (IgAV) is a systemic small-vessel vasculitis in which renal involvement indicates severity of illness, and chronic kidney disease represents the most serious long-term complication. No treatment at present is specifically recommended for IgAV. Recently, rituximab (RTX) has been shown to be effective in case series of adults with IgAV. However, long term results are lacking. Aim of the study is to evaluate the effectiveness of RTX as induction therapy and maintenance of remission in adults with severe IgAV and aggressive glomerulonephritis.
This study included 12 adult-onset patients, 8 males and 4 females, mean age 45.1 years (range 19-75) with a mean follow-up duration of 33.7 months (range 6-144). All patients had a severe IgAV with biopsy proven crescentic nephritis. RTX was given for the treatment of a refractory disease or because of definite contraindications to standard therapies.
Eleven patients (91.7%) achieved a clinical response at 6 months. Ten patients had a complete response (CR) while one had a partial response and was given an additional dose of RTX after 12 months for persistent proteinuria (1gr/24 hrs) despite systemic remission. He achieved a CR 6 months later. One patient was considered unresponsive to RTX and was switched to MMF. Among the 10 patients with CR, 1 needed maintenance doses of RTX every 6 months for iterative relapsing of severe purpura, 1 relapsed after 15 months and received a new induction course showing a CR again. A significant decrease in BVAS (p=0.031) and 24-hour-proteinuria (p=0.043) from RTX initiation through the last follow-up has been detected. One patient, who had a CR with RTX alone died after 6 months for therapy-unrelated cardiovascular cause.
RTX proved to be effective and safe for induction and maintenance of long-lasting remission in severe IgAV with aggresive renal involvement. Data also suggest that RTX can be indicated not only for refractory cases, but can be also proposed as a first line therapy.
免疫球蛋白 A 血管炎（IgAV）是一种系统性小血管血管炎，其中肾脏受累表明疾病的严重程度，而慢性肾脏病是最严重的长期并发症。目前尚无专门针对 IgAV 的治疗方法。最近，利妥昔单抗（RTX）已被证明在成人 IgAV 的病例系列中有效。然而，长期结果尚不清楚。本研究的目的是评估 RTX 作为诱导治疗和维持成人严重 IgAV 和侵袭性肾小球肾炎缓解的疗效。
本研究纳入 12 例成年发病患者，男 8 例，女 4 例，平均年龄 45.1 岁（19-75 岁），平均随访时间 33.7 个月（6-144 个月）。所有患者均有严重的 IgAV，且肾活检证实为新月体肾炎。RTX 用于治疗难治性疾病或由于标准治疗的明确禁忌证。
11 例患者（91.7%）在 6 个月时获得临床缓解。10 例患者达到完全缓解（CR），1 例部分缓解，因持续蛋白尿（1gr/24 小时）尽管全身缓解但仍给予额外剂量的 RTX，12 个月后再次给予 RTX，获得 CR。1 例患者被认为对 RTX 无反应，并转换为 MMF。在 10 例 CR 患者中，1 例因严重紫癜反复发作需要每 6 个月维持剂量的 RTX，1 例在 15 个月后复发，再次接受新的诱导治疗后再次获得 CR。从 RTX 开始到最后一次随访，BVAS（p=0.031）和 24 小时蛋白尿（p=0.043）显著下降。1 例单独使用 RTX 的 CR 患者在 6 个月后因与治疗无关的心血管原因死亡。
RTX 对严重伴有侵袭性肾受累的 IgAV 的诱导和维持长期缓解有效且安全。数据还表明，RTX 不仅可用于难治性病例，也可作为一线治疗药物。
