阿达木单抗治疗难治性白塞病葡萄膜炎的临床研究

Effects of adalimumab in the treatment of refractory Behcet′s uveitis

目的探讨阿达木单抗(ADA)对难治性白塞病葡萄膜炎(BU)的临床疗效。方法收集2020年5月至2021年10月在首都医科大学附属北京同仁医院眼科中心使用ADA治疗难治性BU患者10例(20只眼)进行研究。其中,男性8例(16只眼),女性2例(4只眼),年龄为22~62岁,平均年龄(37.0±14.2)岁。初始治疗采用糖皮质激素联合免疫抑制剂治疗。糖皮质激素选用甲泼尼龙片,起始剂量为1mg/kg/d,炎症控制后糖皮质激素逐渐减量,随访时如果炎症复发则糖皮质激素恢复至上次减量时用量。免疫抑制剂中,环孢素(3mg/kg/d)、硫唑嘌呤(2mg/kg/d)或吗替麦考酚(750mg,2次/d),选择一种。ADA治疗前,在患者检查全身状况达标的基础上对于复发性患者或者对传统治疗反应欠佳患者启动ADA疗法。ADA治疗采用皮下注射。初始治疗剂量为80mg,此后为每两周皮下注射40mg。在炎症控制后,改为口服糖皮质激素与免疫抑制剂治疗并逐渐减量。根据眼前节炎症情况局部给予醋酸泼尼松龙滴眼液及半球后注射用甲泼尼龙琥珀酸钠20mg或曲安奈德注射液20mg治疗。使用硫酸阿托品滴眼液或复方托吡卡胺滴眼液进行散瞳。治疗前后检查患眼的最佳矫正视力、眼压、眼前节炎症、玻璃体炎症及视网膜炎症情况,通过光学相干断层扫描检查黄斑形态并记录并发症的发生情况。眼部观察项目的临床数据,全部采用频数和百分比进行描述。结果患者10例(20只眼)诊断为BU的病程为2~22年,平均为(8.9±6.6)年。全部患者在使用ADA治疗6个月后葡萄膜炎均获得控制,玻璃体炎症由3+~4+控制为0~1+。随访6个月,患者10例(20只眼)均无葡萄膜炎复发。视力提高≥2行者4例(8只眼),占40%(8/20);视力提高≥1行者2例(4只眼),占20%(4/20);视力无变化者2例(3只眼),占15%(3/20);视力下降(2只眼视力为无光感)者3例(5只眼),占25%(5/20)。患者10例(20只眼)经ADA治疗后黄斑水肿均减轻或消退,黄斑区神经上皮层水肿厚度减至200μm以下者5例(8只眼),占40%(8/20),出现黄斑前膜者4例(6只眼),占30%(6/20)。在使用ADA治疗患者炎症控制稳定后,甲泼尼龙片可停用者有5例(10只眼),占50%(5/10);甲泼尼龙片可减量至16mg者有5例(10只眼)。免疫抑制剂可停用者有1例(2只眼),占10%(1/10);免疫抑制剂剂量较使用ADA前可减少者有9例(18只眼),占90%(9/10)。在ADA治疗过程中,出现皮肤注射部位疼痛或皮疹者有3例(6只眼),占30%(3/10);未见有其他全身副作用。结论ADA治疗难治性BU安全有效且具有良好的耐受性,可以减少全身糖皮质激素和免疫抑制剂的需用量。

Objective To investigate the efficacy of adalimumab(ADA)on refractory Behcet′s uveitis(BU).Methods Ten patients(20 eyes)diagnosised with refractory BU at the Eye Center of Beijing Tongren Hospital affiliated to Capital Medical University from May 2020 to October 2021 and treated with ADA were collected.Among them,there were 8 males(16 eyes)and 2 females(4 eyes)with an average age of(37.0±14.2)years(ranged from 22 to 62 years).The initial treatment was glucocorticoids combined with immunosuppressants.Methylprednisolone tablets as glucocorticoids,were used an initial dose of 1 mg·kg-1·d-1,then gradually reduced after the inflammation was controlled.If the inflammation recurred during the follow-up,the dose of glucocorticoid was restored to the dosage at the last reduction.Among immunosuppressants,one of cyclosporine(3 mg·kg-1·d-1),azathioprine(2 mg·kg-1·d-1)or mycophenolate(750 mg,twice a day)has to be chosen.Before ADA treatment,the general condition of patients were checked.If they were up to standards,then ADA treated by subcutaneous injection was used to therapy for recurrent patients or patients with poor response to traditional treatment.The initial dosage of ADA for treatment was 80 mg,followed by subcutaneous injection of 40 mg every two weeks.After the patient′s inflammation was reduced,oral glucocorticoids and immunosuppressants were gradually reduced.Patients were treated by local prednisolone acetate eye drops and retrohemispheric injection of 20 mg methylprednisolone sodium succinate or 20 mg triamcinolone acetonide injection according to the inflammation of the anterior segment.Atropine sulfate eye drops or compound tropicamide eye drops were used for mydriasis.Before and after treatment,the best corrected visual acuity,intraocular pressure,anterior segment inflammation,vitreous inflammation and retinal inflammation of the affected eyes were examined;the macular morphology was evaluated by optical coherence tomography,and the occurrence of complications was recorded and described by frequency and percentage.Results The course of ten patients(20 eyes)diagnosed as BU was 2 to 22 years with an average of(8.9±6.6)years.After ADA treatment for 6 months,uveitis was reduced in all patients.The vitreous inflammation was transferred from 3+~4+to 0~1+.Following up for 6 months,they had no recurrence of uveitis.there were 4 cases(8 eyes)with visual acuity improvement≥2 lines,accounting for 40%(8/20);2 cases(4 eyes)with visual acuity improved≥1 line,accounting for 20%(4/20);2 cases(3 eyes)with no change in visual acuity,accounting for 15%(3/20);3 cases(5 eyes)with visual acuity decreased(2 eyes with no light perception),accounting for 25%(5/20).The macular edema of 10 patients(20 eyes),was reduced or subsided after ADA treatment.There were 5 patients(8 eyes)with the thickness of macular neuroepithelial edema was reduced to less than 200μm,accounting for 40%(8/20).There were 4 patients(6 eyes)with epiretinal membrane,accounting for 30%(6/20).After treating patients using ADA,the inflammation was reduced.Then there were 5 cases(10 eyes)with discontinued methylprednisolone tablets,accounting for 50%(5/10);5 cases(10 eyes)with reduced to 16 mg methylprednisolone tablets.There were 1 case(2 eyes)with discontinued immunosuppressant,accounting for 10%(1/10);9 cases(18 eyes)with reduced dosage of immunosuppressant,accounting for 90%(9/10).During ADA treatment,there were 3 cases(6 eyes)with skin injection site pain or rash,accounting for 30%(3/10).There were no found other systemic side effects.Conclusions ADA is safe,effective and well tolerated in the treatment of refractory BU,which could reduce the demand dose for systemic glucocorticoids and immunosuppressants.