利妥昔单抗治疗天疱疮的长期疗效及安全性分析

Long-term effectiveness and safety of rituximab for the treatment of pemphigus

目的探讨利妥昔单抗(RTX)治疗天疱疮患者的长期疗效和安全性及对免疫指标的影响。方法回顾性纳入2008年2月至2017年7月于北京大学第一医院皮肤科使用RTX(375 mg/m2体表面积,每周1次,连续使用4周)治疗的天疱疮患者。收集基线及不同随访时间点患者的自身抗体、B细胞水平,分析其变化趋势及与疗效的关系。采用Kaplan-Meier方法分析疾病控制、完全缓解和复发情况,对重复测量的免疫指标(自身抗体、B细胞)计算中位数M和P25、P75,绘制随访时间-免疫指标中位水平曲线。结果共纳入53例汉族天疱疮患者,包括40例寻常型天疱疮和13例落叶型天疱疮,男女比例为0.96∶1,中位年龄37.4岁,基线时中位病程为13.4个月,中位随访时间(P25,P75)为37.5(25.0,54.7)个月。疾病控制48例(90.6%),疾病控制时间为1.7(1.1,3.2)个月。完全缓解38例(71.7%),完全缓解时间13.1(9.6,27.5)个月。随访期间完全缓解的38例中复发12例(31.6%),复发时间为12.4(4.8,19.8)个月。随访时间-免疫指标中位水平曲线显示,皮疹缓解时抗Dsg1和Dsg3自身抗体水平下降;皮疹复发时,自身抗体水平上升。最常见的重度不良反应为肺部感染,死亡率为3.8%(2/53)。结论使用RTX治疗天疱疮患者的长期疗效显著,最需关注的不良反应为肺部感染,自身抗体水平可作为RTX治疗天疱疮的疗效观察指标。

Objective To assess the long-term effectiveness and safety of rituximab(RTX)for the treatment of pemphigus,and to evaluate the effect of RTX on immune indices.Methods A retrospective study was conducted,and patients with pemphigus who received monotherapy or combination therapy with RTX(375 mg/m2 body surface area,once a week for 4 consecutive weeks)were collected from the Department of Dermatology,Peking University First Hospital from February 2008 to July 2017.Levels of autoantibodies and proportion of B cells in patients were determined at baseline and different follow-up time points,and their changes and relationship with therapeutic effect were analyzed.Time-to-event outcomes(disease control,complete remission and relapse)were estimated using the Kaplan-Meier method.The median(M)as well as 25th(P25)and 75th(P75)percentile values were calculated for repeatedly measured immune indices(autoantibodies and B cells),and the median level of immune indice-time curve was drawn.Results A total of 53 patients of Han nationality with pemphigus were included,including 40 with pemphigus vulgaris and 13 with pemphigus foliaceus.The male to female ratio was 0.96∶1,the median age was 37.4 years,and the median duration of disease was 13.4 months at baseline.The median follow-up duration(P25,P75)was 37.5(25.0,54.7)months.Forty-eight(90.6%)patients achieved disease control,and the time to disease control was 1.7(1.1,3.2)months.Thirty-eight(71.7%)patients achieved complete remission,and the time to complete remission was 13.1(9.6,27.5)months.During the follow up,12 of the 38(31.6%)patients who had complete remission experienced recurrence,with the time to recurrence being 12.4(4.8,19.8)months.The median immune indice level-time curve showed that anti-Dsg1 and Dsg3 autoantibody levels decreased when skin lesions resolved,but increased when skin lesions relapsed.The most common severe adverse reaction was pulmonary infection,with a mortality rate of 3.8%(2/53).Conclusions RTX shows marked long-term effectiveness for the treatment of pemphigus.Pulmonary infection during treatment is worthy of the highest attention.The autoantibody levels can serve as an index for evaluating the effectiveness of RTX in the treatment of pemphigus.