Ribi Camillo, Cohen Pascal, Pagnoux Christian, Mahr Alfred, Arène Jean-Pierre, Puéchal Xavier, Carli Philippe, Kyndt Xavier, Le Hello Claire, Letellier Philippe, Cordier Jean-François, Guillevin Loïc
Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Université Paris Descartes, 75679 Paris, France.
Arthritis Rheum. 2010 Apr;62(4):1186-97. doi: 10.1002/art.27340.
To assess the efficacy of systemic corticosteroids alone as first-line treatment of polyarteritis nodosa (PAN) and microscopic polyangiitis (MPA) without poor-prognosis factors as defined by the Five-Factors Score (FFS), and to compare the efficacy and safety of azathioprine versus pulse cyclophosphamide as adjunctive immunosuppressive therapy for patients experiencing treatment failure or relapse.
This prospective, multicenter, therapeutic trial included 124 patients with newly diagnosed PAN or MPA (FFS of 0) treated with corticosteroids alone. At the time of treatment failure or disease relapse, patients were randomized to receive 6 months of therapy with oral azathioprine or 6 pulses of cyclophosphamide. Analyses was performed according to an intent-to-treat strategy.
The mean +/- SD followup period was 62 +/- 33 months. Treatment with corticosteroids alone induced remission in 98 patients; 50 (40%) of these patients had sustained disease remission, 46 (37%) experienced a relapse, and 2 became corticosteroid dependent (daily prednisone dose > or = 20 mg). In 26 patients (21%), treatment with corticosteroids alone failed, and 49 patients (40%) required additional immunosuppression. Among the 39 patients randomized, 13 of 19 achieved remission with cyclophosphamide pulses, and 14 of 20 achieved remission with azathioprine. Among all patients, the 1-year and 5-year survival rates were 99% and 92%, respectively. Six deaths occurred in the cyclophosphamide-treated group compared with 2 deaths in the azathioprine-treated group. Disease-free survival was significantly lower for patients with MPA than for those with PAN (P = 0.046).
For patients with PAN or MPA with an FFS of 0, overall 5-year survival was good, but first-line corticosteroid treatment was able to achieve and maintain remission in only about half of the patients, and 40% of the patients required additional immunosuppressive therapy. Azathioprine or pulse cyclophosphamide was fairly effective for treating corticosteroid-resistant disease or major relapses.
评估单纯使用全身糖皮质激素作为无五因素评分（FFS）所定义的不良预后因素的结节性多动脉炎（PAN）和显微镜下多血管炎（MPA）的一线治疗的疗效，并比较硫唑嘌呤与环磷酰胺脉冲疗法作为治疗失败或复发患者辅助免疫抑制治疗的疗效和安全性。
这项前瞻性、多中心治疗试验纳入了124例新诊断的PAN或MPA（FFS为0）且仅接受糖皮质激素治疗的患者。在治疗失败或疾病复发时，患者被随机分配接受6个月的口服硫唑嘌呤治疗或6次环磷酰胺脉冲治疗。分析按照意向性治疗策略进行。
平均±标准差随访期为62±33个月。仅用糖皮质激素治疗使98例患者获得缓解；其中50例（40%）患者疾病持续缓解，46例（37%）复发，2例成为糖皮质激素依赖型（每日泼尼松剂量≥20mg）。26例（21%）患者仅用糖皮质激素治疗失败，49例（40%）患者需要额外的免疫抑制治疗。在随机分组的39例患者中,19例接受环磷酰胺脉冲治疗的患者中有13例缓解，20例接受硫唑嘌呤治疗的患者中有14例缓解。在所有患者中，1年和5年生存率分别为99%和92%。环磷酰胺治疗组有6例死亡，硫唑嘌呤治疗组有2例死亡。MPA患者的无病生存率显著低于PAN患者（P = 0.046）。
对于FFS为0的PAN或MPA患者，总体5年生存率良好，但一线糖皮质激素治疗仅能使约一半的患者实现并维持缓解，40%的患者需要额外的免疫抑制治疗。硫唑嘌呤或环磷酰胺脉冲疗法对于治疗糖皮质激素抵抗性疾病或严重复发相当有效。
