Rituximab for Autoimmune Retinopathy

利妥昔单抗治疗自身免疫性视网膜病变

• 批准号: 8556865
• 负责人: Hatice Sen
• 金额: $ 4.87万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8556865
• 关键词: Acute; Adverse event; Antibodies; Antigens; Area; Autoantibodies; Autoimmune Process; B-Lymphocytes; Binding; Blindness; Case Study; Clinic; Clinical Management; Color Visions; Controlled Clinical Trials; Disease; Electroretinography; Enrollment; Eye; Fluorescein Angiography; Freezing; Functional disorder; Fundus; Goals; Human; Immunologics; Immunosuppression; Immunosuppressive Agents; Infection; Inflammatory; Infusion procedures; Letters; Macaca mulatta; Measurement; Mediating; Night Blindness; Optical Coherence Tomography; Outcome; Outcome Measure; Participant; Patients; Population Study; Quality of life; Questionnaires; Retina; Retinal; Retinal Diseases; Safety; Scotoma; Serum; Severities; Staining method; Stains; Symptoms; Toxic effect; Vertebrate Photoreceptors; Vision; Visit; Visual; Visual Acuity; Visual Fields; base; design; effective therapy; experience; follow-up; improved; meetings; primary outcome; response; rituximab; success

Objective: Autoimmune retinopathy (AIR) is an ophthalmic disorder in which autoantibodies damage the retina and its components, causing progressive vision loss. AIR has no established treatment, but systemic immunosuppression has shown favorable responses. Rituximab is an immunosuppressive agent which binds specifically to B lymphocytes. The objective of this study is to investigate the safety of rituximab as an effective treatment for AIR. Study Population: Five participants with AIR and visual acuity of 20/200 or better in at least one eye will receive rituximab. AIR must be confirmed by immunohistochemical demonstration of serum anti-retinal antibodies on normal, unfixed, frozen rhesus monkey or human retinas, as well as visual field and electroretinography (ERG) changes. Up to seven participants may be enrolled in order to obtain the five participants to be included in the analysis if participants withdraw prior to receiving rituximab. Design: The study duration is 18 months. Rituximab is administered as a cycle consisting of two separate rituximab infusions of 1,000 mg each, two weeks apart. Participants will receive their first rituximab cycle at baseline and evaluated for a second cycle six months later. Treatment success is defined as experiencing a ≥ 25% improvement in ERG response amplitudes or ≥ 3 decibel (dB) improvement in mean deviation on Humphrey Field Analyzer HFA (30-2) or improvement in threshold values > 0.5 log in the existing scotomas on Goldmann Visual Field (GVF) or ≥ 25% improvement in the area of scotomas on GVF assessment as compared with baseline. As a result, participants could receive a maximum of two cycles in this study. Participants will return to the clinic six weeks and three months after their first infusion of each cycle for a safety visit. Study visits will continue every three months for the study duration. Outcome Measures: The primary outcome is the number of participants who meet the definition of treatment success within six months from baseline. Secondary efficacy outcomes include changes in visual acuity, the number of treatment successes at 9 and 12 months, the number of partial responders at 6, 9 and 12 months, changes in ERG or visual field as demonstrated by the HFA (30-2) or GVF, changes in optical coherence tomography (OCT), changes in fluorescein angiography (FA), changes in serum anti-retinal autoantibody or anti-retinal antibody staining, changes in color vision, positive visual symptoms or nyctalopia and changes in the participants quality-of-life as assessed by the NEI visual function questionnaire. For participants with ≥ 2 ERG measurements available prior to enrollment, an attempt will be made to compare the rate of decline pre-study period to the rate of decline post-enrollment period. Safety outcomes include the number and severity of systemic and ocular toxicities, adverse events, and infections and the proportion of participants with a loss of ≥ 15 ETDRS letter score.

目的：自身免疫性视网膜病变(AIR)是一种自身抗体损害视网膜及其组成部分，导致进行性视力丧失的眼科疾病。AIR还没有既定的治疗方法，但全身免疫抑制已显示出良好的反应。利妥昔单抗是一种免疫抑制剂，能与B淋巴细胞特异性结合。本研究的目的是探讨利妥昔单抗作为治疗空气的有效药物的安全性。 研究人群：5名至少一只眼的空气和视力达到20/200或更高的参与者将接受利妥昔单抗治疗。AIR必须通过正常、未固定、冰冻的恒河猴或人视网膜的血清抗视网膜抗体的免疫组织化学显示，以及视野和视网膜电信号(ERG)的变化来确认。如果参与者在接受利妥昔单抗之前退出，则最多可招募7名参与者，以获得纳入分析的5名参与者。 设计：研究时间为18个月。利妥昔单抗是一个周期，由两次单独的利妥昔单抗输注组成，每次1000毫克，间隔两周。参与者将在基线时接受第一个利妥昔单抗周期，并在六个月后进行第二个周期的评估。治疗成功的定义是：与基线相比，ERG反应幅度改善25%或Humphrey视野分析仪HFA(30-2)的平均偏差改善3分贝(30-2)，或Goldmann视野(GVF)现有暗点的阈值&gt；0.5log改善或GVF评估的暗点面积改善25%。因此，在这项研究中，参与者最多可以接受两个周期。参与者将在每个周期的第一次输液后六周和三个月返回诊所进行安全访问。在研究期间，每三个月将继续进行一次考察访问。 结果衡量：主要结果是从基线起6个月内符合治疗成功定义的参与者的数量。二次疗效结果包括视力的变化，9个月和12个月的治疗成功次数，6，9和12个月的部分应答者数量，视网膜电信号或视野的变化，如HFA(30-2)或GVF显示的变化，光学相干断层扫描(OCT)的变化，荧光血管造影(FA)的变化，血清抗视网膜自身抗体或抗视网膜抗体染色的变化，色觉的变化，阳性视觉症状或夜视，以及由NEI视觉功能问卷评估的参与者生活质量的变化。对于在注册前有ERG测量的参与者，将尝试比较研究前和注册后的下降率。安全结果包括全身和眼部毒性、不良事件和感染的数量和严重程度，以及失去ETDRS字母评分的参与者的比例。