利妥昔单抗治疗小儿神经系统自身免疫病的疗效分析
|
摘要
目的探讨神经系统自身免疫病患儿应用利妥昔单抗(RTX)疗效及安全性。方法选取云南省昆明市儿童医院收治的难治复发性神经系统自身免疫病40例,比较RTX治疗前后的残疾状态量表评分、年复发率(ARR)、血常规及免疫球蛋白的差异,同时监测B淋巴细胞亚群的变化。结果患者RTX治疗前后锥体系功能、膀胱直肠功能、视觉功能及脑干功能比较,差异有统计学意义(P <0.05);治疗后ARR较治疗前降低(P<0.05);患者RTX治疗前后IgG、IgM及IgA比较,差异有统计学意义(P<0.05);治疗后CD19~+较治疗前降低(P<0.05),不良反应发生率为35%。结论 RTX可改善难治复发性神经系统自身免疫病患儿的临床症状,偶有发热、寒战等不良反应,可能是难治复发性神经系统自身免疫病的有效药物。
Objective To investigate and analyze the efficacy and safety of Rituximab in children with neurological autoimmune diseases. Methods Forty cases of refractory and recurrent autoimmune diseases of nervous system admitted to our hospital were selected. Differences in Disability Status Scale(EDSS) score, annual recurrence rate(ARR), blood routine indexes(platelets, WBC, Hct and Hb), and immunoglobins before and after Rituximab treatment were compared; changes in B lymphocyte subsets were monitored. Results The differences in pyramidal function, bladder and rectum function, visual function and brainstem function before and after Rituximab treatment were statistically significant(P < 0.05). The ARR decreased significantly after treatment(P < 0.05). There were significant differences in IgG, IgM, and IgA before and after treatment(P < 0.05). The number of CD19~+ lymphocytes after treatment was significantly smaller than that before treatment(P < 0.05). The incidence of adverse reactions was 35%. Conclusions Rituximab can improve the long-term clinical symptoms in patients with recurrent and refractory autoimmune diseases in the nervous system, with occasional adverse reactions such as fever and chills. It may be an effective drug to treat autoimmune diseases of nervous system that are refractory and recurrent.
Objective To investigate and analyze the efficacy and safety of Rituximab in children with neurological autoimmune diseases. Methods Forty cases of refractory and recurrent autoimmune diseases of nervous system admitted to our hospital were selected. Differences in Disability Status Scale(EDSS) score, annual recurrence rate(ARR), blood routine indexes(platelets, WBC, Hct and Hb), and immunoglobins before and after Rituximab treatment were compared; changes in B lymphocyte subsets were monitored. Results The differences in pyramidal function, bladder and rectum function, visual function and brainstem function before and after Rituximab treatment were statistically significant(P < 0.05). The ARR decreased significantly after treatment(P < 0.05). There were significant differences in IgG, IgM, and IgA before and after treatment(P < 0.05). The number of CD19~+ lymphocytes after treatment was significantly smaller than that before treatment(P < 0.05). The incidence of adverse reactions was 35%. Conclusions Rituximab can improve the long-term clinical symptoms in patients with recurrent and refractory autoimmune diseases in the nervous system, with occasional adverse reactions such as fever and chills. It may be an effective drug to treat autoimmune diseases of nervous system that are refractory and recurrent.
引文
[1]张黎.大剂量丙种球蛋白、甲基氢化泼尼松治疗神经系统自身免疫性疾病的观察与护理[J].吉林医学, 2014, 35(12):2687.
[2]SHERMAN E, HAN MH. Acute and chronic management of neuromyelitis optica spectrum disorder[J]. Cur Treat Options Neurol, 2015, 17(11):48.
[3]李燕,王晓敏,毛敏,等.小剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症的临床观察[J].中华血液学杂志, 2012,33(3):204-206.
[4]傅卓,包新华,吴晔,等.利妥昔单抗在儿童神经系统自身免疫性疾病中的应用[J].中国儿科杂志, 2017, 55(9):689-694.
[5]STONE JH, MERKEL P A, SPIERA R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis[J]. N Engl J Med, 2010, 363(3):221-232.
[6]AKAISHI T,NAKASHIMAI.Rituximab(anti-CD20)in neurological disorders[J]. Brain Nerve, 2014, 66(10):1167-1178.
[7]ZEPHIR H, BERNARD-VALNET R, LEBRUN C, et al. Rituximab as first-line therapy in neuromyelitis optica:efficiency and tolerability[J]. J Neurol, 2015, 262(10):2329-2335.
[8]贾立明,景永峰,武卫周,等.血浆置换与血浆免疫吸附对神经系统自身免疫性疾病的疗效与不良反应分析[J].中国实用医药, 2016, 11(16):12-13.
[9]韦潋滟,秦新月.免疫吸附治疗急性炎症性脱髓鞘性多发性神经病疗效观察[J].重庆医科大学学报, 2010, 35(1):88-90.
[10]MOGHADDASIM, AGHAEIM. Assessmentofbone densitometry in Iranian patients with multiple sclerosis:a casecontrol study[J]. Iran J Neurol, 2013, 12(1):9-14.
[11]TOBIN W O, PITTOCK S J. Rituximab therapy in neuromyelitis opticamoving toward a personalized medicine[J]. JAMA Nurol,2015, 72(9):974-977.
[12]BRABIM H, MAZEN M, DIMACBKIE, et al. A review:the use of rituximab in neuromuscular diseases[J]. Clin Neuromus Dis,2010, 12(2):9l-94.
[13]张隽,陈海,康海娟,等.利妥昔单抗治疗5例难治性视神经脊髓炎谱系疾病长期疗效观察[J].中国神经免疫学和神经病学杂志, 2016, 23(4):235-239.
[14]都娟,黄建萍,王硕,等.利妥昔单抗在小儿频复发肾病综合征中的应用[J].中华实用儿科临床杂志, 2014, 29(9):659-662.
[15]SALZER J, LYCKE J, WICKSTROM R, et al. Rituximab in paediatric onset multiple sclerosis:a case series[J]. J Neurol,2016, 263(2):322-326.
[16]WEINER G J. Rituximab:mechanism of action[J]. Semin Hematol, 2010, 47(2):115-123.
[17]LONGONI G, BANWELL B, FILIPPI M, et al. Rituximab as a first-line preventive treatment in pediatric NMOSDs:preliminary results in 5 children[J]. Neurol Neuroimmunol Neuroinflamm,2014, 1(4):46.
[18]WINGERCHUK DM, BANWELL B, BENNETT JL,etal.International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J]. Neurology, 2015, 85(2):177-189.
[19]PAPADOPOULOS MC, BENNETT JI, VERKMAN AS.Treatment of neuromyelitis optica:state-of-the-art and emerging therapies[J]. Nat Rev Neurol, 2014, 10(9):493-506.
[20]张春涛,张美妮.利妥昔单抗在视神经脊髓炎及其谱系疾病中作用的探讨[J].中华脑科疾病与康复杂志:电子版, 2015,5(6):416-419.
[21]BATTAGLIA T, de GRANDIA E, MIRABELLI-BADENIER M, et al. Response to rituximab in 3 children with opsoclonusmyoclonus syndrome resistant to conventional treatments[J]. Eur J Paediatr Neurol, 2012, 16(2):192-195.
[22]MITCHELL WG, WOOTEN A A, NEIL SH, et al. Effect of increased immunosuppression on development outcome of opsoclonus myoclonus syndrome(OMS)[J]. J Child Neurol,2015, 30(8):976-982.
[23]DANéS A. AGUSTI?A. VALLANO J. Available evidence and outcome of off-label use of rituximabin clinical practical[J].European Journal of Clinical Pharmacology, 2013, 69(9):1689-1699.
[24]GEA-BANACLOCHE J C. Rituximab-associated infections[J].Seminars in Hem-atology, 2010, 47:187-198.
[2]SHERMAN E, HAN MH. Acute and chronic management of neuromyelitis optica spectrum disorder[J]. Cur Treat Options Neurol, 2015, 17(11):48.
[3]李燕,王晓敏,毛敏,等.小剂量利妥昔单抗治疗复发难治性原发免疫性血小板减少症的临床观察[J].中华血液学杂志, 2012,33(3):204-206.
[4]傅卓,包新华,吴晔,等.利妥昔单抗在儿童神经系统自身免疫性疾病中的应用[J].中国儿科杂志, 2017, 55(9):689-694.
[5]STONE JH, MERKEL P A, SPIERA R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis[J]. N Engl J Med, 2010, 363(3):221-232.
[6]AKAISHI T,NAKASHIMAI.Rituximab(anti-CD20)in neurological disorders[J]. Brain Nerve, 2014, 66(10):1167-1178.
[7]ZEPHIR H, BERNARD-VALNET R, LEBRUN C, et al. Rituximab as first-line therapy in neuromyelitis optica:efficiency and tolerability[J]. J Neurol, 2015, 262(10):2329-2335.
[8]贾立明,景永峰,武卫周,等.血浆置换与血浆免疫吸附对神经系统自身免疫性疾病的疗效与不良反应分析[J].中国实用医药, 2016, 11(16):12-13.
[9]韦潋滟,秦新月.免疫吸附治疗急性炎症性脱髓鞘性多发性神经病疗效观察[J].重庆医科大学学报, 2010, 35(1):88-90.
[10]MOGHADDASIM, AGHAEIM. Assessmentofbone densitometry in Iranian patients with multiple sclerosis:a casecontrol study[J]. Iran J Neurol, 2013, 12(1):9-14.
[11]TOBIN W O, PITTOCK S J. Rituximab therapy in neuromyelitis opticamoving toward a personalized medicine[J]. JAMA Nurol,2015, 72(9):974-977.
[12]BRABIM H, MAZEN M, DIMACBKIE, et al. A review:the use of rituximab in neuromuscular diseases[J]. Clin Neuromus Dis,2010, 12(2):9l-94.
[13]张隽,陈海,康海娟,等.利妥昔单抗治疗5例难治性视神经脊髓炎谱系疾病长期疗效观察[J].中国神经免疫学和神经病学杂志, 2016, 23(4):235-239.
[14]都娟,黄建萍,王硕,等.利妥昔单抗在小儿频复发肾病综合征中的应用[J].中华实用儿科临床杂志, 2014, 29(9):659-662.
[15]SALZER J, LYCKE J, WICKSTROM R, et al. Rituximab in paediatric onset multiple sclerosis:a case series[J]. J Neurol,2016, 263(2):322-326.
[16]WEINER G J. Rituximab:mechanism of action[J]. Semin Hematol, 2010, 47(2):115-123.
[17]LONGONI G, BANWELL B, FILIPPI M, et al. Rituximab as a first-line preventive treatment in pediatric NMOSDs:preliminary results in 5 children[J]. Neurol Neuroimmunol Neuroinflamm,2014, 1(4):46.
[18]WINGERCHUK DM, BANWELL B, BENNETT JL,etal.International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J]. Neurology, 2015, 85(2):177-189.
[19]PAPADOPOULOS MC, BENNETT JI, VERKMAN AS.Treatment of neuromyelitis optica:state-of-the-art and emerging therapies[J]. Nat Rev Neurol, 2014, 10(9):493-506.
[20]张春涛,张美妮.利妥昔单抗在视神经脊髓炎及其谱系疾病中作用的探讨[J].中华脑科疾病与康复杂志:电子版, 2015,5(6):416-419.
[21]BATTAGLIA T, de GRANDIA E, MIRABELLI-BADENIER M, et al. Response to rituximab in 3 children with opsoclonusmyoclonus syndrome resistant to conventional treatments[J]. Eur J Paediatr Neurol, 2012, 16(2):192-195.
[22]MITCHELL WG, WOOTEN A A, NEIL SH, et al. Effect of increased immunosuppression on development outcome of opsoclonus myoclonus syndrome(OMS)[J]. J Child Neurol,2015, 30(8):976-982.
[23]DANéS A. AGUSTI?A. VALLANO J. Available evidence and outcome of off-label use of rituximabin clinical practical[J].European Journal of Clinical Pharmacology, 2013, 69(9):1689-1699.
[24]GEA-BANACLOCHE J C. Rituximab-associated infections[J].Seminars in Hem-atology, 2010, 47:187-198.