Lancet:10年研究显示利妥昔单抗治疗寻常型天疱疮可获得长期的疗效

2016-01-09 sunshine MedSci原创

寻常型天疱疮是一种潜在的致命的自身免疫性大疱性疾病,病损波及皮肤和粘膜。研究发现,使用利妥昔单抗治疗寻常型天疱疮可取得令人激动的效果,利妥昔单抗原本适用于治疗淋巴瘤或类风湿性关节炎的药物。在这些研究中,无论何种状况的患者都会同时接受全身糖皮质激素和免疫抑制剂治疗。经此治疗,大部分患者的临床症状在几周内便可明显缓解。但是,从病例报告和病例系列分析所得的数据显示, 50-80%的患者可复发。利妥昔单抗

寻常型天疱疮是一种潜在的致命的自身免疫性大疱性疾病,病损波及皮肤和粘膜。研究发现,使用利妥昔单抗治疗寻常型天疱疮可取得令人激动的效果,利妥昔单抗原本适用于治疗淋巴瘤或类风湿性关节炎的药物。在这些研究中,无论何种状况的患者都会同时接受全身糖皮质激素和免疫抑制剂治疗。经此治疗,大部分患者的临床症状在几周内便可明显缓解。但是,从病例报告和病例系列分析所得的数据显示, 50-80%的患者可复发。利妥昔单抗和免疫抑制治疗所延长的免疫抑制期可产生一些副作用,尤其是感染,可能会进展为败血症或导致死亡的发生。

2006年,静脉注射免疫球蛋白和利妥昔单抗联合应用,用于治疗11例严重和顽固性寻常型天疱疮患者。该联合应用包括输注利妥昔单抗10次,治疗6个月以上,以及每月静脉注射免疫球蛋白,直到B细胞的水平恢复正常。以前地,长期的、全身的、高剂量的糖皮质激素,多免疫抑制剂,以及静脉注射免疫球蛋白的治疗未能控制这些患者的疾病的进展。随着新的治疗方法的应用,所有的患者出现了令人惊喜的改善,症状完全缓解可持续3年以上,这些患者直至文献发表也未接受一步的治疗。

这里,我们报告一个10年的随访研究结果(111-136个月,平均131.7个月),随访始于患者用利妥昔单抗。(1名患者在首次研究发表后失去了随访,因此最近的研究包括10名患者)

这10名患者的病情仍处于缓解期,无一例复发。在这10年的随访期间,我们并没有观察到患者出现短期或长期的不良事件,因而无需住院治疗。经利妥昔单抗或静脉注射免疫球蛋白治疗后,患者并未出现其他的自身免疫性疾病,癌症,或死亡。IgG自身抗体(显示寻常型天疱疮的存在)在2006年患者经过治疗后检测显示阴性,现在检测依然是阴性。2006年,CD19+B细胞计数显示处于正常水平,在这之后也一直处于正常水平。最后一次应用利妥昔单抗治疗后5年,行皮肤活检(曾经的病损部位),使用直接免疫荧光法检测并未出现寻常型天疱疮的表现。

这种联合治疗所带来的10年缓解效果的机制尚未清楚。鉴于利妥昔单抗可破坏致病性B细胞,静脉注射免疫球蛋白或可有助于修复免疫调节和正常生理机能。

原始出处:

Srini Kaveri, Long-Term Remissions in Recalcitrant Pemphigus Vulgaris. N Engl J Med 2015; 373:2693-2694December 31, 2015DOI: 10.1056/NEJMc1508234

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    2016-12-02 howi
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