Predictors of relapse and treatment resistance in antineutrophil cytoplasmic anti body-associated small-vessel vasculitis
Predictors of relapse and treatment resistance in antineutrophil cytoplasmic anti body-associated small-vessel vasculitis
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DOI：
10.7326/0003-4819-143-9-200511010-00005
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发表时间：
2005-11-01
影响因子：
39.2
通讯作者：
Nachman, PH
中科院分区：
文献类型：
--
作者：
Hogan, SL;Falk, RJ;Nachman, PH
背景：在抗中性粒细胞胞浆抗体(ANCA)相关的小血管炎中，治疗耐药和复发的预测因素尚未得到很好的描述。目的：在ANCA相关小血管炎患者的社区队列中，确定临床、病理和血清学对治疗耐药和复发的预测因素。设计：在活检诊断时或接近活检诊断时确定的患者队列，并根据临床指示进行随访。地点：肾小球疾病协作网络。患者：350名患者，他们在1985-2003年间接受了ANCA相关性脉管炎的新诊断，并进行了中位数49个月的随访。测量：根据患者是否有抗蛋白酶-3(抗PR3)抗体或抗髓过氧化物酶(抗MPO)抗体对患者进行分类。器官受累通过活检或明确的临床标准来确定。治疗抵抗被定义为肾功能进行性下降并伴有活跃的尿沉渣或持续或出现肾外表现。结果：在接受治疗的334例患者中，23%的患者存在治疗抵抗，并与女性、黑人和合并严重肾脏疾病有关(每例血清肌酐升高100MU/L的优势比为1.13 mg/dL，1.28[95%CI，1.16~1.39])。在258例(77%)获得缓解的患者中，以下因素与复发有关：抗PR3抗体血清阳性(危险比1.87[CI，1.11至3.14])和肺部疾病(危险比1.71[CI，1.04至2.81])或上呼吸道疾病(危险比1.73[CI，1.04至2.88])。在没有危险因素的患者中，26%的患者复发，而在所有三种危险因素的患者中，复发率为73%(危险比，3.7[CI，1.4至9.7])。在143名随后停止所有免疫抑制剂治疗的获得缓解的患者中，接受环磷酰胺治疗6个月或更短时间的患者的复发率(34%)与接受更长时间治疗的患者(35%)相似，即使在调整了复发的危险因素后也是如此(危险比，1.41[CI，0.80至2.50])。限制：队列主要包括经生物检查证实的肾脏疾病患者。患者没有遵循统一的治疗方案，在诊断之前只有有限的关于他们的临床过程的信息。结论：女性或黑人患者，或患有严重肾脏疾病的患者，可能比其他ANCA相关性小血管炎患者更容易抵制初始治疗。复发风险的增加似乎与肺部或上呼吸道疾病的存在以及抗PR3抗体阳性有关。
Background: Predictors of treatment resistance and relapse have not been well described in antineutrophil cytoplasmic antibody (ANCA)-associated small-vessel vasculitis.Objective: To identify clinical, pathologic, and serologic predictors of treatment resistance and relapse in a community-based cohort of patients with ANCA-associated vasculitis. Design: Cohort of patients identified at or near the time of biopsy diagnosis and followed as clinically indicated.Setting: The Glomerular Disease Collaborative Network. Patients: 350 patients who received a new diagnosis of ANCA-associated vasculitis between 1985 and 2003 and were followed for a median of 49 months. Measurements: Patients were categorized according to whether they had antiproteinase-3 (anti-PR3) antibodies or antimyeloperoxidase (anti-MPO) antibodies. Organ involvement was determined by biopsy or by well-defined clinical criteria. Treatment resistance was defined as progressive decline in kidney function with active urine sediment or the persistence or appearance of extrarenal manifestations. Relapse was defined as the time to the resurgence of vasculitic symptoms.Results: Treatment resistance affected 23% of 334 treated patients and was associated with female sex, black ethnicity, and presentation with severe kidney disease (odds ratio per serum creatinine elevation of 100 mu mol/L [1.13 mg/dL], 1.28 [95% Ci, 1.16 to 1.39]). The following factors were associated with relapse in 258 (77%) patients who attained remission: seropositivity for anti-PR3 antibodies (hazard ratio, 1.87 [Cl, 1.11 to 3.14]) and disease of the lung (hazard ratio, 1.71 [Cl, 1.04 to 2.81]) or upper respiratory tract (hazard ratio, 1.73 [Cl, 1.04 to 2.88]). Relapses occurred in 26% of patients with no risk factors versus 73% of patients with all 3 risk factors (hazard ratio, 3.7 [Cl, 1.4 to 9.7]). Among 143 patients attaining remission who subsequently stopped all immunosuppressant therapy, relapse rates were similar for those who had received cyclophosphamide therapy for 6 months or less (34%) compared with those treated for a longer duration (35%), even after adjusting for risk factors for relapse (hazard ratio, 1.41 [Cl, 0.80 to 2.50]).Limitations: The cohort mostly included patients with biopsyproven kidney disease. Patients were not followed with uniform treatment protocols, and only limited information about their clinical course before diagnosis was available.Conclusions: Female or black patients, or those with severe kidney disease, may be resistant to initial treatment more often than other patients with ANCA-associated small-vessel vasculitis. increased risk for relapse appears to be related to the presence of lung or upper airway disease and anti-PR3 antibody seropositivity.