Universita di Torino, Torino, Italy.
Nephrol Dial Transplant. 2011 Dec;26(12):3987-92. doi: 10.1093/ndt/gfr109. Epub 2011 Mar 8.
B cells play a central role in systemic lupus erythematosus (SLE). Rituximab is expected to induce apoptosis of all the CD20-positive B cells. A proportion of patients are refractory or intolerant to standard immunosuppression. These are candidate to new therapeutic options.
Eight patients [six women, two men, mean age 41-year-old (27-51), with severe multiorgan involvement (kidney, skin, nervous system, polyarthritis, polyserositis, antiphospholipid antibody syndrome)] were considered eligible for an intensive combination therapy including rituximab. Rituximab was administered (dose 375 mg/m(2)) on Days #2, 8, 15 and 22. Two more doses were administered 1 and 2 months following the last weekly infusion. This treatment was combined with two pulses of 750 mg cyclophosphamide (Days #4 and 17) and three pulses of 15 mg/kg (Days #1, 4 and 8) methylprednisolone followed by oral prednisone, 50 mg for 2 weeks rapidly tapered until 5 mg in 2 months. Response was evaluated by assessing the changes in clinical signs and symptoms [Systemic Lupus Erythematosus Disease Activity Index (SLEDAI score)] and laboratory parameters for at least 12 months.
Levels of erythrocyte sedimentation rate and anti-double-strand DNA antibodies significantly decreased (P < 0.01 at 12 months), whereas C3 and mainly C4 values increased at 6 months (P < 0.01 for C4). Proteinuria improved in the cases with renal involvement (P < 0.01 at 3, 6 and 12 months). SLEDAI score improved moving from the mean 17.3 (12-27) before therapy to 3.1 (1-5) after rituximab treatment. Constitutional symptoms including arthralgia, weakness and fever disappeared in all the previously affected patients; paresthesia improved in the four patients with polyneuropathy and skin lesions gradually resolved in the patients with necrotizing skin ulcers at presentation. Drug side effects were negligible.
Long-lasting remissions were obtained in patients with severe SLE and major organ involvement by this intensive administration of rituximab combined with low doses of intravenous cyclophosphamide and methylprednisolone pulses followed by a rapid tapering of prednisone to 5 mg/day as a sole maintenance therapy.
B 细胞在系统性红斑狼疮（SLE）中起核心作用。利妥昔单抗有望诱导所有 CD20 阳性 B 细胞凋亡。一部分患者对标准免疫抑制治疗有抵抗或不耐受。这些是新治疗方案的候选者。
8 例患者[6 名女性，2 名男性，平均年龄 41 岁（27-51 岁），有严重的多器官受累（肾脏、皮肤、神经系统、多关节炎、多浆膜炎、抗磷脂抗体综合征）]被认为符合包括利妥昔单抗在内的强化联合治疗标准。利妥昔单抗（剂量 375mg/m2）于第 2、8、15 和 22 天给药。末次每周输注后 1 个月和 2 个月时再给予 2 次剂量。该治疗与 2 个周期 750mg 环磷酰胺（第 4 和 17 天）和 3 个周期 15mg/kg（第 1、4 和 8 天）甲泼尼龙联合使用，随后口服泼尼松，2 周内快速减至 5mg，2 个月内减至 5mg。通过评估至少 12 个月的临床症状和体征[系统性红斑狼疮疾病活动指数（SLEDAI 评分）]和实验室参数的变化来评估应答。
红细胞沉降率和抗双链 DNA 抗体水平显著下降（12 个月时 P < 0.01），而 C3 和主要 C4 值在 6 个月时升高（C4 的 P < 0.01）。有肾脏受累的病例蛋白尿改善（3、6 和 12 个月时 P < 0.01）。SLEDAI 评分从治疗前的平均 17.3（12-27）改善至治疗后的 3.1（1-5）。所有先前受累的患者均出现关节痛、乏力和发热等全身症状消失；4 例多发性神经病患者出现感觉异常改善，初诊时出现坏死性皮肤溃疡的患者皮肤病变逐渐消退。药物副作用可忽略不计。
通过利妥昔单抗的强化给药联合低剂量静脉环磷酰胺和甲泼尼龙脉冲治疗，随后快速减至 5mg/天的泼尼松单药维持治疗，在患有严重 SLE 和主要器官受累的患者中获得了持久缓解。
