利妥昔单抗治疗难治性重症系统性红斑狼疮的临床初步观察

Efficacy of rituximab in patients with refractory severe systemic lupus erythematosus

目的初步观察利妥昔单抗治疗难治性重症系统性红斑狼疮(SLE)的疗效及不良反应。方法难治性重症SLE 15例(神经精神狼疮6例,狼疮肾炎4例,免疫性血小板减少5例),予静脉滴注利妥昔单抗500mg,使用1～4次,同时依据病情联合使用激素等免疫抑制剂。采用BILAG和系统性红斑狼疮疾病活动指数(SLEDAI)积分对病情进行评价,监测不良反应及外周血B细胞清除情况和血清学指标变化。结果利妥昔单抗治疗难治性重症SLE,至随访终点BILAG临床完全缓解、部分缓解和无缓解分别占总例数的33%,40%和27%。其中神经精神狼疮和免疫性血小板减少临床改善显著,起效时间≤1个月,部分患者可获得长期缓解(>12个月);入组狼疮肾炎患者效果不佳。研究期间共发生4例严重感染,并导致2例死亡。结论初步提示利妥昔单抗对部分难治性重症SLE有效,该生物制剂可能成为SLE新的诱导缓解手段之一。由于尚缺乏有力的循证医学指导,临床应用需谨慎从事。尤需警惕免疫抑制状态继发感染问题。

Objecave To investigate the clinical efficacy and adverse effects ot ntuximab m patients with refractory severe systemic lupus erythematosus （SLE）. Methods Fifteen patients with refractory severe SLE enrolled in this open-labeled uncontrolled trial were further divided into three subsets, i.e., neuropsychiatric SLE （NPSLE, n=6）, lupus nephritis（LN, n=4）, autoimmune thrombocytopenia purpura （ITP, n=5）. One to four doses of rituximab （500 mg per dose） was given intravenously, in combination with corticosteroids and immunosuppressive drugs as needed for patient＇s condition. SLE activity was evaluated by the systemic lupus erytbematosus disease activity index （SLEDAI） and the British isles lupus assessment group index （BILAG）. Adverse events, peripheral blood CD19^＋B cells, and serology markers were documented. Results The overall responsiveness of Rituximab were gauged by BILAG-based complete remission, partial remission, non-remission rates, which are 33%, 40% and 27%, respectively. Significant clinical improvement was noted, with rapid improvement of refractory NPSLE and ITP （≤ 1 month）, and some patients experi- enced long-term remission （〉12 months）. LN patients, however, showed a poor responsiveness. Four cases of infections as severe adverse events were observed, which lead to 2 deaths. Conclusion Rituximab appeared to be a promising induction treatment for certain forms of refractory severe SLE. In lack of sufficient evidence-based data, cautious must be made for its clinical application. The risk of infections should always be taken into consideration.