Dammacco F, Della Casa Alberighi O, Ferraccioli G, Racanelli V, Casatta L, Bartoli E
Department of Biomedical Sciences and Human Oncology, University of Bari, Policlinico, Italy.
Int J Clin Lab Res. 2000;30(2):67-73. doi: 10.1007/s005990070017.
The positive results obtained with cyclosporine-A both in an experimental model and in selected patients with advanced systemic lupus erythematosus support the hypothesis that the drug could be used as a steroid sparer in the earliest stages of active disease. To determine the 12-month clinical efficacy (disease control and steroid sparing), safety, and tolerability of low-dose cyclosporine-A plus steroids versus steroids alone, we designed a multicenter, open, prospective, randomized, pilot study, controlled for parallel groups. The patients were then followed up to month 24. A total of 18 consenting patients with recently diagnosed systemic lupus erythematosus of moderate severity indicated for the use of steroids in acute boluses and subsequently per os were enrolled at two university hospital medical centers. The protocol was based on three 1-g boluses of 6-methylprednisolone followed by cyclosporine-A (<5 mg/kg per day) plus prednisone 0.5-1 mg/kg per day per os, reduced by 5 mg/day every 2 weeks following clinical remission, versus the same doses of oral prednisone alone. The efficacy evaluation was based on a four-point scale (from absent/none to severe) for signs and symptoms of systemic lupus erythematosus and immunoserological parameters. The disease activity index and cumulative prednisone dose per patient were analyzed. Any adverse events were reported. All patients showed a reduction in disease activity index within the 1st month. The results were significantly better in the group with cyclosporine-A plus prednisone throughout month 12 (baseline and 12-month disease activity indexes: 21.3+/-8.6 and 5.0+/-2.5 versus 20.4+/-7.1 and 8.8+/-6.0 in the prednisone group, P<0.05). The 12-month cumulative mean dose of prednisone was significantly lower in the group with both cyclosporine-A plus prednisone (179.4+/-40.1 versus 231.8+/-97.1 mg/kg, P<0.005). No unusual adverse events related to the study drugs have been reported. In particular, renal function and blood pressure monitoring revealed no significant changes from mean baseline values in either group. No disease flares were reported in the group treated with cyclosporine-A plus prednisone during the 12- to 24-month period. Thus cyclosporine-A represents a useful corticosteroid sparer in the maintenance of clinical remission in patients with an early-stage, active systemic lupus erythematosus.
环孢素A在实验模型以及部分晚期系统性红斑狼疮患者中取得的阳性结果支持了以下假说：在活动性疾病的最早阶段，该药物可作为类固醇替代药物使用。为了确定低剂量环孢素A联合类固醇与单纯使用类固醇相比，在12个月时的临床疗效（疾病控制和类固醇节省效应）、安全性及耐受性，我们设计了一项多中心、开放、前瞻性、随机对照的试点研究。随后对患者进行随访至24个月。共有18名新近诊断为中度严重程度系统性红斑狼疮且同意参与研究的患者入组，这些患者因急性发作需大剂量使用类固醇，随后口服给药，研究在两家大学医院医学中心开展。研究方案为给予3次1g剂量的甲泼尼龙冲击治疗，随后给予环孢素A（每日剂量<5mg/kg）联合泼尼松每日口服0.5 - 1mg/kg，临床缓解后每2周将泼尼松剂量减少5mg/天，对照组为单纯给予相同剂量的口服泼尼松。疗效评估基于系统性红斑狼疮的体征和症状以及免疫血清学参数的四分制量表（从无/无到严重）。分析每位患者的疾病活动指数和累积泼尼松剂量。报告任何不良事件。所有患者在第1个月内疾病活动指数均有所降低。在整个12个月期间，环孢素A联合泼尼松组的结果明显更好（基线和12个月时的疾病活动指数：分别为21.3±8.6和5.0±2.5，泼尼松组为20.4±7.1和8.8±6.0，P<0.05）。环孢素A联合泼尼松组12个月的泼尼松累积平均剂量显著更低（分别为179.4±40.1和231.8±97.1mg/kg，P<0.005）。未报告与研究药物相关的异常不良事件。特别是，肾功能和血压监测显示两组的平均基线值均未出现显著变化。在12至24个月期间，环孢素A联合泼尼松治疗组未报告疾病复发。因此，环孢素A在维持早期活动性系统性红斑狼疮患者的临床缓解方面是一种有用的皮质类固醇替代药物。
