Efficacy of rituximab orbital injection combined with intravenous drip of methylprednisolone in treating Graves' ophthalmopathy and its influence on immune system
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摘要:目的
探讨利妥昔单抗(RTX)眼眶注射联合甲泼尼龙静脉滴注对甲状腺眼病(Graves眼病)的治疗效果。
方法将2021年7月—2023年1月资阳市人民医院收治的102例Graves眼病患者随机分为联合组(n=34)、甲泼尼龙组(n=34)和RTX组(n=34)。甲泼尼龙组给予糖皮质激素(甲泼尼龙)单药, RTX组给予RTX单药，联合组给予RTX联合甲泼尼龙。比较3组总有效率、眼征状况、甲状腺体积、甲状腺免疫抗体[抗甲状腺球蛋白抗体(TGAb)、抗促甲状腺素受体抗体(TRAb)、抗甲状腺过氧化物酶抗体(TPOAb)水平]、临床活动度量表(CAS)评分、外周血免疫球蛋白[免疫球蛋白G4(IgG4)、IgG4/IgG]水平及不良反应。
结果联合组总有效率为97.06%(33/34), 高于甲泼尼龙组的79.41%(27/34)和RTX组的76.47%(26/34), 差异有统计学意义(P < 0.05)。治疗4、8周后，联合组眼球突出度、球尖距、眼内压、球后软组织体积均低于甲泼尼龙组、RTX组，差异有统计学意义(P < 0.05); 联合组甲状腺体积、CAS评分均低于甲泼尼龙组、RTX组，差异有统计学意义(P < 0.05); 联合组TGAb、TRAb、TPOAb均低于甲泼尼龙组、RTX组，差异有统计学意义(P < 0.05); 联合组IgG4、IgG4/IgG均低于甲泼尼龙组、RTX组，差异有统计学意义(P < 0.05)。3组不良反应发生比较，差异无统计学意义(P>0.05)。
结论Graves眼病患者接受RTX眼眶注射联合甲泼尼龙静脉滴注可获得更好的疗效，有利于改善眼征状况，调节TGAb、TRAb、TPOAb及免疫球蛋白。
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关键词:
- Graves眼病 /
- 利妥昔单抗 /
- 糖皮质激素 /
- 抗甲状腺球蛋白抗体 /
- 抗促甲状腺素受体抗体 /
- 抗甲状腺过氧化物酶抗体
Abstract:ObjectiveTo explore the efficacy of rituximab (RTX) orbital injection combined with intravenous drip of methylprednisolone in treating Graves' ophthalmopathy.
MethodsA total of 102 patients with Graves' ophthalmopathy in the Ziyang City People's Hospital from July 2021 to January 2023 were randomly divided into combination group (n=34), methylprednisolone group (n=34), and RTX group (n=34). The methylprednisolone group was given glucocorticoids (methylprednisolone) monotherapy, the RTX group was given RTX monotherapy, and the combination group was given RTX combined with methylprednisolone. The total effective rate, ophthalmic manifestations, thyroid volume, thyroid immune antibodies [thyroid globulin antibody (TGAb), thyrotropin receptor antibody (TRAb) and thyroid peroxidase antibody (TPOAb) levels], the Clinical Activity Scale (CAS), levels of immunoglobulins in peripheral blood [immunoglobulin G4 (IgG4) and IgG4/IgG], and adverse reactions were compared among the three groups.
ResultsThe total effective rate was 97.06%(33/34) in the combination group, which was significantly higher than 79.41%(27/34) in the methylprednisolone group and 76.47%(26/34) in the RTX group (P < 0.05). After 4 and 8 weeks of treatment, the exophthalmos degree, interocular distance, intraocular pressure, and retrobulbar soft tissue volume in the combination group were significantly lower than those in the methylprednisolone group and the RTX group (P < 0.05); the thyroid volume and the CAS score in the combination group were significantly lower than those in the methylprednisolone group and the RTX group (P < 0.05); the TGAb, TRAb and TPOAb levels in the combination group were significantly lower than those in the methylprednisolone group and the RTX group (P < 0.05); the IgG4 and IgG4/IgG in the combination group were significantly lower than those in the methylprednisolone group and the RTX group (P < 0.05). There was no significant difference in the incidence of adverse
ConclusionsFor patients with Graves' ophthalmopathy, therapeutic effect of RTX orbital injection combined with intravenous drip of methylprednisolone is better, which is beneficial for improving ophthalmic manifestations and regulating levels of TGAb, TRAb, TPOAb and immunoglobulins.
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表 1 3组一般资料比较（x±s）[n(%)]
组别 n 性别 年龄/岁 体质量指数/(kg/m2) 病程/月 病情分级 男 女 中度 重度 联合组 34 18(52.94) 16(47.06) 41.25±3.52 21.79±1.04 8.35±1.14 19(55.88) 15(44.12) 甲泼尼龙组 34 19(55.88) 15(44.12) 40.93±3.81 22.08±1.11 8.28±1.29 21(61.76) 13(38.24) RTX组 34 17(50.00) 17(50.00) 41.47±3.75 21.92±0.96 8.08±1.42 20(58.82) 14(41.18) χ2/F 0.236 0.184 0.665 0.402 0.243 P 0.889 0.833 0.516 0.670 0.886 
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表 2 3组眼内压与眼球突出度比较（x±s）
组别 n 眼内压/mmHg 眼球突出度/mm 治疗前 治疗4周 治疗8周 治疗前 治疗4周 治疗8周 联合组 34 18.62±3.48 17.08±2.15 16.09±2.02 19.18±3.18 17.25±1.78 16.78±1.06 甲泼尼龙组 34 18.75±3.54 18.32±2.26* 17.70±2.12* 19.15±3.41 18.16±1.85* 17.94±0.95* RTX组 34 18.69±3.51 18.19±2.18* 17.73±2.07* 19.13±3.16 18.35±1.92* 17.99±0.93* 与联合组比较, * P < 0.05。
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表 3 3组球尖距与球后软组织体积比较（x±s）
组别 n 球尖距/mm 球后软组织体积/cm3 治疗前 治疗4周 治疗8周 治疗前 治疗4周 治疗8周 联合组 34 24.10±2.83 22.46±1.47 22.01±0.88 9.68±1.28 7.89±0.99 7.60±0.97 甲泼尼龙组 34 24.15±2.74 23.04±1.62* 22.83±1.30* 9.75±1.33 8.46±1.03* 8.18±1.10* RTX组 34 24.13±2.73 23.43±1.59* 22.90±1.16* 9.69±1.42 8.59±1.17* 8.25±1.04* 与联合组比较, * P < 0.05。
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表 4 3组甲状腺体积、CAS评分比较（x±s）
组别 n 甲状腺体积/mm3 CAS评分/分 治疗前 治疗4周 治疗8周 治疗前 治疗4周 治疗8周 联合组 34 32.15±4.91 27.17±2.25 26.37±2.06 6.32±0.60 5.38±0.72 4.46±0.83 甲泼尼龙组 34 32.63±5.66 28.72±2.88* 28.34±2.82* 6.42±0.63 5.96±0.69* 5.47±0.77* RTX组 34 32.45±5.27 28.90±2.91* 28.38±2.65* 6.37±0.58 5.78±0.65* 5.43±0.76* CAS: 临床活动性量表。与联合组比较, * P < 0.05。
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表 5 3组甲状腺免疫抗体水平比较（x±s）
mIU/mL 指标 时点 联合组(n=34) 甲泼尼龙组(n=34) RTX组(n=34) TGAb 治疗前 62.31±4.95 63.08±5.06 63.14±4.98 治疗4周 58.18±2.32 61.22±3.65* 61.03±3.34* 治疗8周 54.42±3.11 57.20±2.86* 57.35±3.04* TRAb 治疗前 46.95±4.37 46.18±3.88 46.46±4.12 治疗4周 27.86±2.47 31.45±3.54* 31.79±3.48* 治疗8周 22.12±2.32 27.15±3.80* 26.48±3.27* TPOAb 治疗前 39.25±5.20 38.78±5.63 38.85±5.34 治疗4周 32.48±2.65 35.95±3.83* 35.76±3.54* 治疗8周 28.96±2.22 31.37±3.54* 32.10±2.79* TGAb: 抗甲状腺球蛋白抗体; TRAb: 抗促甲状腺素受体抗体; TPOAb: 抗甲状腺过氧化物酶抗体。与联合组比较, * P < 0.05。
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表 6 3组外周血免疫球蛋白水平比较（x±s）
组别 n IgG4/(mg/dL) IgG4/IgG/% 治疗前 治疗4周 治疗8周 治疗前 治疗4周 治疗8周 联合组 34 134.40±32.15 97.82±23.60 78.89±20.74 12.02±2.28 9.10±2.04 7.69±1.38 甲泼尼龙组 34 126.42±29.64 109.63±22.15* 88.32±18.65* 11.31±2.67 10.15±1.96* 8.54±1.52* RTX组 34 130.51±31.25 114.69±20.64* 92.24±19.38* 11.84±2.54 10.56±1.88* 8.94±1.57* IgG4: 免疫球蛋白G4; IgG: 免疫球蛋白G。与联合组比较, * P < 0.05。
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表 7 3组不良反应比较[n(%)]
组别 n 低热 腹胀恶心 消化道溃疡 合计 联合组 34 2(5.88) 1(2.94) 1(2.94) 4(11.76) 甲泼尼龙组 34 2(5.88) 1(2.94) 0 3(8.82) RTX组 34 1(2.94) 2(5.88) 1(2.94) 4(11.76)
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