Hoffman G S, Leavitt R Y, Fleisher T A, Minor J R, Fauci A S
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, Maryland 20892.
Am J Med. 1990 Oct;89(4):403-10. doi: 10.1016/0002-9343(90)90367-m.
Concerns regarding the long-term toxicity of daily cyclophosphamide (CP) therapy for the systemic vasculitides have led us to evaluate alternative approaches to treatment in an attempt to achieve comparable efficacy with less toxicity. This study sought to determine the efficacy, toxicity, and immunologic effects of glucocorticoids (GC) and intermittent high-dose intravenous CP ("pulse" CP) in the treatment of 14 patients with Wegener's granulomatosis (WG).
The diagnosis of active WG was supported by a typical clinical presentation and histopathologic findings of vasculitis, granulomatous inflammation, and tissue necrosis. GC treatment was initially provided on a daily basis and later tapered to an alternate-day schedule if vasculitis remained inactive. Pulse CP treatment was initially administered once a month for 6 months. If after 6 months remission had been attained and GC therapy had been discontinued, then pulse CP treatment was given at less frequent intervals thereafter. Treatment and evaluation were provided for participants as inpatients in a clinical research center (National Institutes of Health).
Thirteen of 14 patients (93%) initially experienced unequivocal improvement with pulse CP therapy, and seven of 14 (50%) achieved remission within 4 months. However, treatment was associated with significant toxicity in two patients and later relapses in nine patients, so that a total of 79% either failed to achieve sustained remission or were unable to continue therapy. Three of 14 (21%) patients have achieved sustained remissions with the pulse CP protocol and one additional patient (who had a limited exacerbation of WG) continues to receive that therapy after 14 to 22 months (mean 17 months).
The use of pulse CP and GC therapy in 14 patients with WG was associated with a high initial response rate. However, failure to respond initially to treatment, to sustain improvement, or to tolerate continued treatment was noted in 79% of patients within a period of 1 to 22 months. These observations indicate that this particular pulse CP protocol does not achieve a high degree of lasting efficacy.
对于环磷酰胺（CP）每日疗法治疗系统性血管炎的长期毒性的担忧，促使我们评估替代治疗方法，以期在降低毒性的同时获得相当的疗效。本研究旨在确定糖皮质激素（GC）和间歇性大剂量静脉注射CP（“冲击”CP）治疗14例韦格纳肉芽肿（WG）患者的疗效、毒性及免疫效应。
典型的临床表现以及血管炎、肉芽肿性炎症和组织坏死的组织病理学发现支持活动性WG的诊断。GC治疗最初每日给药，若血管炎保持非活动性，则随后逐渐减为隔日给药方案。冲击CP治疗最初每月给药1次，共6个月。若6个月后病情缓解且已停用GC治疗，则此后冲击CP治疗给药间隔延长。在临床研究中心（美国国立卫生研究院），对参与者作为住院患者进行治疗和评估。
14例患者中有13例（93%）最初接受冲击CP治疗后有明确改善，14例中有7例（50%）在4个月内实现缓解。然而，治疗导致2例患者出现显著毒性反应，9例患者随后复发，因此总计79%的患者未能实现持续缓解或无法继续治疗。14例患者中有3例（21%）通过冲击CP方案实现了持续缓解，另有1例患者（WG病情有局限性加重）在14至22个月（平均17个月）后继续接受该治疗。
14例WG患者使用冲击CP和GC治疗，初始缓解率较高。然而，在1至22个月内，79%的患者出现了对治疗初始无反应、无法维持改善或无法耐受持续治疗的情况。这些观察结果表明，这种特定的冲击CP方案未能达到高度持久的疗效。
