Université Paris Descartes and Hôpital Cochin, AP-HP, Paris, France.
Hôpital Hôtel-Dieu, Paris, France.
Arthritis Rheumatol. 2016 Mar;68(3):690-701. doi: 10.1002/art.39450.
Findings from the WEGENT trial and other short-term studies have suggested that azathioprine (AZA) or methotrexate (MTX) could effectively maintain remission of granulomatosis with polyangiitis (Wegener's) (GPA) or microscopic polyangiitis (MPA). This study was undertaken to examine whether differences in rates of relapse or adverse events would appear after discontinuation of these 2 maintenance regimens, when assessed over a longer followup period.
Long-term outcomes in patients enrolled in the WEGENT trial were analyzed according to their randomized treatment group (AZA or MTX). Parameters at trial entry were evaluated as potential prognostic factors for death, relapse, or damage in multivariate models.
Data from 10 years of followup were available for 112 (88.8%) of the 126 original trial participants. The median followup time was 11.9 years (95% confidence interval [95% CI] 11.3-12.5 years). In patients receiving AZA and those receiving MTX, the 10-year overall survival rates were 75.1% (95% CI 64.8-86.9%) and 79.9% (95% CI 70.3-90.8%) (P = 0.56), respectively, and relapse-free survival rates were 26.3% (95% CI 17.3-40.1%) and 33.5% (95% CI 23.5-47.7%) (P = 0.29), respectively. No between-treatment differences were observed with regard to rates of relapse, adverse events, damage, survival without severe side effects, and survival without relapse and severe side effects. In analyses limited to the 97 patients with GPA, no between-treatment differences in survival rates were observed. The 10-year relapse-free survival rate was lower in patients with GPA than in patients with MPA. However, in the multivariate analysis, anti-proteinase 3 antineutrophil cytoplasmic antibody (ANCA) positivity, and not GPA, was retained as being independently associated with the relapse rate.
The results of this long-term analysis confirm that AZA and MTX are comparable treatment options for maintaining remission of GPA or MPA. Despite achieving good overall survival with these treatments, relapse rates, adverse events, and damage remain matters of concern and further studies are needed to reduce their frequency in these ANCA-associated vasculitides.
WEGENT 试验和其他短期研究的结果表明，硫唑嘌呤（AZA）或甲氨蝶呤（MTX）可有效维持肉芽肿性多血管炎（韦格纳氏）（GPA）或显微镜下多血管炎（MPA）的缓解。本研究旨在探讨在更长的随访期内，评估停用这两种维持治疗方案后，复发率或不良事件是否会出现差异。
根据随机治疗组（AZA 或 MTX）分析参加 WEGENT 试验的患者的长期结局。在多变量模型中，评估试验入组时的参数是否为死亡、复发或损害的潜在预后因素。
126 名原始试验参与者中有 112 名（88.8%）可获得 10 年随访的数据。中位随访时间为 11.9 年（95%置信区间[95%CI]11.3-12.5 年）。在接受 AZA 和 MTX 的患者中，10 年总生存率分别为 75.1%（95%CI64.8-86.9%）和 79.9%（95%CI70.3-90.8%）（P=0.56），无复发生存率分别为 26.3%（95%CI17.3-40.1%）和 33.5%（95%CI23.5-47.7%）（P=0.29）。在复发率、不良事件、损害、无严重副作用生存和无复发及严重副作用生存方面，未观察到治疗间差异。在仅包括 97 名 GPA 患者的分析中，未观察到生存率的治疗间差异。与 MPA 患者相比，GPA 患者的 10 年无复发生存率较低。然而，在多变量分析中，抗蛋白酶 3 抗中性粒细胞胞质抗体（ANCA）阳性，而不是 GPA，被保留为与复发率独立相关的因素。
这项长期分析的结果证实，AZA 和 MTX 是维持 GPA 或 MPA 缓解的可比较治疗选择。尽管这些治疗方法总体生存良好，但复发率、不良事件和损害仍然是值得关注的问题，需要进一步研究以降低这些抗中性粒细胞胞质抗体相关性血管炎的发生频率。
