利妥昔单抗单药或联合糖皮质激素治疗Graves眼病的有效性和安全性研究

Efficacy and safety of rituximab alone or combined with glucocorticoid in the treatment of Graves′ ophthalmopathy

目的比较糖皮质激素(GCs)、利妥昔单抗(RTX)以及GCs联合RTX治疗中重度活动性Graves眼病(GO)的有效性与安全性。方法纳入2017年8月至2019年7月于江苏省中西医结合医院内分泌科就诊的GO患者42例,分为GCs组(18例)、RTX组(7例)、联合组(17例)。GCs组,予甲泼尼龙500 mg静滴,每周1次×6周;随后250 mg静滴,每周1次×6周。RTX组,予RTX 100 mg静滴,每2周1次,共2次。联合组,即上述RTX联合甲泼尼龙脉冲治疗。治疗后12周、24周,评估各组患者临床活动性评分(CAS)和NOSPECS分级;比较促甲状腺受体抗体转归情况;记录不良事件。结果GCs组、RTX组、联合组CAS评分下降2分及以上或评分小于3分的比例分别为88.9%、85.7%、100.0%,3组间比较差异无统计学意义(P=0.321)。治疗后24周,3组患者CAS评分、NOSPECS分级较治疗前均明显下降(P<0.05);联合组CAS评分下降幅度大于GCs组(-3.12±1.02对-2.39±1.02,P=0.036)及RTX组(-3.12±1.02对-2.14±0.90,P=0.034)。联合组有1例患者在治疗后24周出现视神经病变,余患者未发生严重不良事件。结论小剂量RTX单药治疗活动性中重度GO的效果不劣于静脉GCs。GCs联合RTX治疗在改善患者的CAS评分方面比两药单用效果更佳。

Objective To compare the efficacy and safety of glucocorticoids(GCs),rituximab(RTX),and GCs combined with RTX in the treatment of active moderate-to-severe Graves′ophthalmopathy(GO).Methods A total of 42 patients with GO who were hospitalized in the Endocrinology Department of Jiangsu Integrated Traditional Chinese and Western Medicine Hospital from August 2017 to July 2019 were included and divided into GCs group(18 cases),RTX group(7 cases),GCs combined with RTX group(17 cases).Patients in the GCs group were received 500 mg intravenous methylprednisolone once a week for 6 weeks,followed by 250 mg intravenous methylprednisolone once a week for 6 weeks.In RTX group,patients were given intravenous RTX 100 mg every 2 weeks for 2 times.GCs combined with RTX group,i.e.RTX combined with methylprednisolone pulse therapy.At 12 and 24 weeks after treatment,CAS and NOSPECS classes were evaluated in each group.The altered course of thyroid stimulating receptor antibody were compared among the three groups.All adverse events were recorded.Results The proportion of CAS decreased≥2 or total scores<3 points in the GCs,RTX and combined groups were 88.9%,85.7%and 100%,with no statistical difference among the three groups(P=0.321).At 24 weeks,CAS and NOSPECS classes decreased significantly in all three groups compared with those before treatment(P<0.05).The reduction of CAS in the combined group was greater than in the GCs group(-3.12±1.02 vs-2.39±1.02,P=0.036)and RTX group(-3.12±1.02 vs-2.14±0.90,P=0.034).One patient in the combined group developed optic neuropathy at 24 weeks after treatment,all other patients had no severe adverse events.Conclusion Low-dose RTX alone is not inferior to intravenous GCs in the treatment of active moderate to severe GO.GCs combined with RTX is more effective in improving patients′CAS than either drugs alone.