A Randomized, Open-Label, 2-Arm, 2-Part, Parallel Group Study to Assess the Pharmacokinetic Comparability of Subcutaneously Administered Litifilimab (BIIB059) Delivered by 3 Devices (Pre-Filled Syringe, Autoinjector, or On-Body Injector) in Healthy Participants

In this study, researchers will learn how the body processes litifilimab when it is given under the skin in 3 different ways. Currently, ongoing studies utilize pre-filled syringes (PFS) that can deliver litifilimab subcutaneously (SC), also known as under the skin.
In this study, researchers want to learn more about new ways of delivering litifilimab SC using either an autoinjector (AI) or an on-body injector (OBI):
Both devices are designed to deliver litifilimab in an automatic way, especially helping patients who may not be able to use their hands very well, or who may be afraid of needles. While the AI is handheld, the OBI device works by being placed on the skin and can help deliver the highest amount of litifilimab through a single injection. The main objective of this study is to learn how the body processes litifilimab after using the AI device or the OBI device, as compared to using the PFS method.
The main questions researchers want to answer are:
* What is the highest amount of litifilimab found in the blood after dosing? How much total litifilimab is found in the blood throughout the study? Researchers will also learn more about: Any medical problems the participants have during the study
* Any injection site pain or reactions the participants may have. Any skin reactions to the OBI device
* Any changes in the participants' overall health after receiving litifilimab.
This study will be done as follows:
* Participants will be screened to check if they can join the study. The screening period will be up to 4 weeks, after which selected participants will check into their study research center.
* Participants will be randomly assigned to be in Part 1 or Part 2 of the study:
* Part 1: Participants will receive SC injection(s) of litifilimab through either the AI device or through PFS.
* Part 2: Participants will receive SC injection(s) of litifilimab through the OBI device or through PFS.
* Participants will remain at their study research center for the first 8 days. After that, there will be a follow-up period for 17 weeks during which participants return to the center a total of 6 times.
Each participant will be in the study for about 22 weeks.

开始日期2025-01-02

申办/合作机构

Biogen, Inc.

NCT06044337

/ Enrolling by invitation临床3期

A Multicenter, Open-Label, Single-Arm, Phase 3, Long-Term Extension Study to Evaluate Continuous Safety and Efficacy of BIIB059 (Litifilimab) in Adult Participants With Active Subacute Cutaneous Lupus Erythematosus and/or Chronic Cutaneous Lupus Erythematosus With or Without Systemic Manifestations and Refractory and/or Intolerant to Antimalarial Therapy

In this study, researchers will learn more about a study drug called BIIB059 (litifilimab) in participants with cutaneous lupus erythematosus (CLE). The study will focus on participants who have either active subacute CLE or chronic CLE, or both. They may also have systemic lupus erythematosus (SLE). The participants did not respond to antimalarial therapy or had problems with the treatment that made it hard to continue.
The study will enroll only those participants who have completed treatment with litifilimab in the parent study, 230LE301.
The main objective of the study is to learn more about the long-term safety of litifilimab.
The main question researchers want to answer is:
* How many participants have adverse events and serious adverse events after taking litifilimab? Adverse events are health problems that may or may not be caused by the study drug.
Researchers will also learn more about the effect of litifilimab on CLE. They will do this by measuring the symptoms of CLE over time using a variety of scoring tools. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), the Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R), and the SELENA-SLEDAI Flare Index (SFI).
Researchers will look at how litifilimab and CLE affect the quality of life of participants using a group of questionnaires. They will also look at how litifilimab affects laboratory tests and how participants' immune systems respond to litifilimab.
The study will be done as follows:
* The last visit of parent study 230LE301 will be the first visit of study 230LE305.
* All participants will receive litifilimab as an injection under the skin once every 4 weeks. Both researchers and participants will know the dose and identity of the study drug.
* Globally, the treatment period will last up to 208 weeks, or 4 years. Participants will have up to 53 study visits during this time.

开始日期2023-10-03

申办/合作机构

Biogen, Inc.

NCT05531565

/ Active, not recruiting临床2/3期

A 2-Part Seamless Part A (Phase 2)/Part B (Phase 3) Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BIIB059 in Participants With Active Subacute Cutaneous Lupus Erythematosus and/or Chronic Cutaneous Lupus Erythematosus With or Without Systemic Manifestations and Refractory and/or Intolerant to Antimalarial Therapy (AMETHYST)

In this study, researchers will learn more about a study drug called litifilimab (BIIB059) in participants with cutaneous lupus erythematosus (CLE). The study will focus on participants who have either active subacute CLE or chronic CLE, or both. They may also have systemic lupus erythematosus (SLE). The participants did not respond to antimalarial therapy or had problems with the treatment that made it hard to continue.
The main objective of the study is to learn about the effect litifilimab has on lowering the activity of the skin disease. Researchers will measure symptoms and signs of CLE over time using a variety of scoring tools. These include the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI), the Cutaneous Lupus Activity of Investigator's Global Assessment-Revised (CLA-IGA-R), and the SELENA-SLEDAI Flare Index (SFI).
The main questions researchers want to answer are:
* How many participants have a score of 0 or 1 on the CLA-IGA-R looking at skin redness after treatment?
* How many participants have their skin disease activity go down by at least 70% as measured by CLASI?
Researchers will also learn more about the safety of litifilimab. They will study how participants' immune systems respond to litifilimab. Additionally, they will measure the effect litifilimab and CLE have on the quality of life of participants using a group of questionnaires.
The study will be split into 2 parts - Part A and Part B. Both parts will be done as follows:
* After screening, participants will be randomized to receive either litifilimab or placebo for the 1st treatment period. A placebo looks like the study drug but contains no real medicine.
* Participants will receive either litifilimab or placebo as injections under the skin once every 4 weeks.
* The 1st treatment period will be double blinded which means neither the researchers nor the participants will know if the participants are receiving litifilimab or placebo.
* This double blinded treatment period will last 24 weeks, after which the 2nd treatment period will begin.
* During the 2nd treatment period, all participants will receive litifilimab for 28 weeks.
* After completing treatment in this study, participants that qualify will be given the choice to join the Long-Term Extension study, 230LE305. If they do not, they will move into a follow-up safety period that will last up to 24 weeks.
* The total study duration for participants will be up to 80 weeks.

开始日期2022-09-13

申办/合作机构

Biogen, Inc.

100 项与利替非利单抗相关的临床结果

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100 项与利替非利单抗相关的转化医学

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100 项与利替非利单抗相关的专利（医药）

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项与利替非利单抗相关的文献（医药）

2026-04-29·INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Genetic Polymorphisms in Systemic Lupus Erythematosus and Their Clinical Implications: A Narrative Review.

Review

作者: Azizan, Elena Aisha ; Johdi, Nor Adzimah ; Rajalingham, Sakthiswary ; Egan, Audrey Matilda ; Shaharir, Syahrul Sazliyana ; Mohd, Rozita ; Zailani, Mohamed Afiq Hidayat

Systemic lupus erythematosus (SLE) is a polygenic autoimmune disorder where genetic diversity drives significant clinical heterogeneity. This review summarizes the current understanding of the roles of genetic polymorphisms in immunological dysregulation, organ-specific manifestations and therapeutic response heterogeneity in individuals with SLE. The literature was obtained from PubMed, EBSCOhost, Web of Science and Scopus. The narrative review comprised 60 publications published within the last 12 years. The research consistently identifies the major histocompatibility complex (MHC) region as the most significant genetic risk factor for the onset of autoimmunity. Genetic variants in STAT4 and IRF5 exacerbate disease progression by facilitating chronic inflammation. These genetic factors are associated with various clinical outcomes, including renal and neuropsychiatric symptoms. Polymorphisms in HLA class II, TLR7 and FBN2 are notably linked to serious consequences, including lupus nephritis (LN). Progress in targeted therapy signifies a transition to personalized medicine with medications such as anifrolumab, litifilimab, iberdomide and Janus kinase (JAK) or Cyclin-Dependent Kinase (CDK) inhibitors, demonstrating potential for targeting pathways associated with the interferon gene signature and STAT4 polymorphisms. Notwithstanding the problems presented by the heterogeneity of SLE, the identification of risk variations is anticipated to enhance predictive and therapeutic biomarkers, hence facilitating more precise and individualized disease management.

2026-01-01·The Journal of clinical and aesthetic dermatology

What's New in Cutaneous Lupus Erythematosus: Guidelines, Biologics, and Beyond.

Review

作者: Childs, Beth A ; Merola, Joseph F

OBJECTIVE:

We aim to review current treatment strategies for cutaneous lupus erythematosus (CLE) and highlight emerging therapies, evolving outcome measures, and practical considerations that may inform future management of this clinically heterogeneous disease.

METHODS:

We conducted a narrative review of the literature using PubMed to identify relevant clinical trials, observational studies, and mechanistic investigations related to CLE treatment. Emphasis was placed on studies published within the past 15 years. Expert opinion from dermatology and rheumatology was incorporated to contextualize evolving therapies and their application in clinical practice.

RESULTS:

Current management of CLE follows a stepwise framework, with antimalarials and immunosuppressants forming the foundation of systemic therapy. However, many patients experience refractory disease, especially in chronic or hypertrophic subtypes. Advances in the understanding of CLE pathogenesis have led to the development of targeted biologics and small molecule agents that modulate Type I interferon signaling, B- and T-cell activation, and inflammatory cytokine pathways. Novel tools such as Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) and the Investigator Global Assessment for Cutaneous Lupus (CLA-IGA-R) are being validated to standardize disease assessment, while RNA tape sampling and real-world electronic health record (EHR)-based algorithms are enhancing research precision. Emerging therapies, such as belimumab, anifrolumab, litifilimab, deucravacitinib, and enpatoran, demonstrate promise in both clinical trials and real-world settings.

LIMITATIONS:

As a narrative review, this study is limited by the lack of systematic inclusion criteria and formal quality assessment of individual studies.

CONCLUSION:

Ongoing therapeutic innovation, guided by mechanistic insights and strengthened by the development of standardized outcome measures, is transforming the CLE landscape and advancing the goal of precision-based, durable disease control.

2025-12-01·Arthritis & Rheumatology

Pharmacodynamic Effects of Litifilimab in Lupus in a Randomized, Placebo‐Controlled Phase 2 Study: Rapid and Sustained Reductions in Type I Interferon‐Associated Gene Expression and Cytokines

Article

作者: Furie, Richard ; Milliman, Eric ; Franchimont, Nathalie ; Ferber, Kyle ; Werth, Victoria P. ; Barbey, Catherine ; Lahoud, Youmna ; Zoghbi, Jad ; Brown, Roland

Objective:

The pharmacodynamic effects of litifilimab on type I interferon (IFN) response and correlations with clinical outcomes were investigated in systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).

Methods:

Participants from part A (SLE) or part B (CLE with or without SLE) of the randomized phase 2 LILAC trial who received litifilimab (at 50 mg, 150 mg, or 450 mg) or a placebo were included. IFN gene signature (IFNGS) scores were assessed from whole‐blood samples using a 22‐gene panel in 120 and 131 participants (parts A and B, respectively). IFNα and other IFN‐regulated cytokine concentrations were measured in serum in 112 and 131 participants (parts A and B, respectively).

Results:

Most participants were IFNGS‐high at baseline (79–91%), and no baseline IFNGS‐low participant results were reported. In IFNGS‐high participants, litifilimab induced rapid, significant (nominal P < 0.05), and sustained reductions in IFNGS scores and IFNα concentrations versus a placebo for litifilimab at 450 mg in part A and for litifilimab at 150 mg and 450 mg in part B. In part A, IFNα reductions with litifilimab were correlated with clinical response measures. In part B, dose‐response relationships for IFNGS score and IFNα concentration were observed, similar to those for disease activity measured with the Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI‐A) score.

Conclusion:

Administration of litifilimab resulted in reductions in both IFNGS scores and IFNα concentrations, pharmacodynamic effects that correlated with clinical responses. These findings support the mechanism of action of litifilimab and its continued evaluation in larger studies of patients with SLE or CLE.image

152

项与利替非利单抗相关的新闻（医药）

2026-08-16

·肖生客

下半年值得期待的十项临床试验

作者：肖生客 BioPharma Dive每年年中都会列一份"下半年值得关注的临床试验"清单，今年这份，我读了两遍。原因很简单：2026上半年，生物医药行业等了三年终于等来回暖，并购创纪录、IPO复苏、几家公司的重磅数据接连读出。下半年是验证这波回暖成色的时候，而这份清单，就是行业押注的方向盘。我挑几个最值得展开的，说说我看到的门道。第一组：肿瘤的正面战场康方生物和Summit合作的依沃西单抗，下半年有一场硬仗，叫Harmoni-3。这是PD-1/VEGF双抗领域最受关注的一项全球三期试验，头对头对比默沙东的Keytruda加化疗，在一线非小细胞肺癌。这个试验的重要性在于：之前康方和Summit的数据大部分来自中国单中心研究，质疑者一直说"中国数据能不能推广到全球"说不清楚。Harmoni-3是全球多中心，如果能打赢，等于给PD-1/VEGF这个方向在全球定调。有意思的是市场反应。6月ASCO上，中国版的Harmoni-6数据公布，生存获益明确，结果Summit股价反而跌了两位数。为什么？因为分析师盯着一个细节：中国试验里65到75岁患者没有明显获益，而这部分人占美国用药人群的三分之一。市场不是不认可数据，是在挑数据的成色。同一时间，莫德纳和默沙东的个性化肿瘤疫苗intismeran，也在等它的三期关键数据。这个试验叫Interpath-001，黑色素瘤术后辅助治疗，头对头对比Keytruda单药。之前二期数据显示，疫苗加Keytruda能把复发或死亡风险砍掉一半左右，随访五年依然稳固。如果三期能复制，这是肿瘤治疗十年来最大的范式变化之一——从"用药杀肿瘤"变成"训练免疫系统自己杀"。第二组：精神疾病的大市场百时美施贵宝在等Cobenfy的阿尔茨海默病精神病数据，试验叫ADEPT-2。 Cobenfy去年上市，是几十年来第一个全新机制的抗精神病药，治疗精神分裂症。但上市后的销售没达到华尔街预期，去年全年1.55亿美元，今年一季度5600万。BMS现在把宝押在适应症扩展上：阿尔茨海默病精神病。这个市场有多大？美国700万阿尔茨海默患者里，四分之一到一半会出现精神病症状，这是巨大的未满足需求。但ADEPT-2之前出过状况，BMS发现试验在少数中心存在"不合规"，数据读出推迟了。分析师的态度也分裂：有人担心试验失败，有人觉得推迟反而说明BMS在认真做。我的看法：Cobenfy能不能从"精神分裂症新药"变成"神经精神科重磅药"，ADEPT-2就是分水岭。如果失败，BMS会很难受；如果成功，这是它140亿美元收购Karuna之后最值钱的一笔回报。第三组：让行业重新相信基因治疗最值得CGT行业关注的，是诺华的Harbor试验。这是诺华120亿美元收购Avidity之后的核心验证。药物叫del-desiran，治疗强直性肌营养不良1型，这是一种进行性肌肉萎缩的罕见病，美国约8万患者。它的技术路线是抗体偶联RNA——用一个抗体把RNA药物送进肌肉细胞，降低致病蛋白表达。为什么这个试验对CGT行业重要？因为过去几年，核酸药物在肌肉组织递送上一直没突破，全身给药进不了肌肉。Avidity的抗体偶联平台如果被验证，等于给RNA疗法打开了一个新器官的递送大门。诺华CEO纳拉西姆汉已经放话：如果Harbor成功，他们要用扎实的肌肉功能数据抢在竞争对手前面做标准批准，而不是走加速批准。同一赛道的还有渤健的litifilimab，治疗系统性红斑狼疮，两个三期试验TOPAZ-1和TOPAZ-2共入组1100多人，下半年读出。分析师预测峰值销售能超20亿美元。对渤健来说，这是它从神经科学单一依赖里走出来的关键一步。第四组：被忽视的隐形大战还有几个试验，关注度没那么高，但商业分量很重。 Vaxcyte的31价肺炎球菌疫苗，三期试验直接对比辉瑞的Prevnar 20和默沙东的21价。肺炎球菌疫苗是个年销售60亿美元以上的大市场，辉瑞独霸多年。Vaxcyte如果证明非劣，这是几十年来第一次有人真正撼动辉瑞的疫苗堡垒。阿斯利康和Ionis的eplontersen，治疗转甲状腺素蛋白淀粉样变心肌病，7月已经读出数据。这个赛道辉瑞的Vyndamax去年卖了60亿美元，三家竞争者已经进场，第四家能不能分一杯羹，看的是疗效差异化的成色。 BMS和强生合作的milvexian，Factor XI抑制剂，两个三期试验共入组3万人，目标是在房颤和中风预防里挑战Eliquis。这个药之前在急性冠脉综合征上失败过，但抗凝领域"更安全"的叙事依然值几百亿美元。礼来的retatrutide三靶点减肥药，Triumph系列5月已经读出第一个数据，下半年还有两个。这个药在骨关节炎试验里让患者平均减重接近29%，直接把减肥药的天花板掀了。诺和诺德自己的三靶点还在早期临床，至少落后几年。说点大家没关注的这份清单表面上是"哪些试验会读出"，但我的读法不太一样。第一，注意名单里的中国角色。康方生物的依沃西单抗是全球试验的主角，这在五年前不可想象。中国创新药不再是"被引进的对象"，开始成为"定义全球标准的一方"。这是比任何单个数据都重要的信号。第二，注意这些试验的共同点：全是头对头、全是标准治疗升级、全在抢"更好"而不是"有"。行业回暖之后，资本和市场对me-too的容忍度在急剧下降，能进下半年清单的，都是敢跟标准治疗硬碰硬的项目。这给所有做研发的人一个提醒：差异化不是加分项，是入场券。第三，基因治疗和核酸药物在这份清单里占了四席。诺华、渤健、莫德纳、阿斯利康，全是大药企在CGT领域的真金白银。经历了几年的资本寒冬和管线收缩之后，大药企依然在CGT上押注，说明这个方向的长期逻辑没有变，变的只是对执行力的要求。下半年见分晓。这10项试验里，会有改写治疗标准的，也会有让人失望的。但不管结果如何，2026年的生物医药，正在用真数据重新赢回资本和信任。这也是我想说的：行业回暖不是等来的，是每个敢做头对头试验的公司，一步步打出来的。

临床3期疫苗并购临床结果基因疗法

2026-08-12

·网易号

华润双鹤，重磅新药获批临床

，最新观察： ‌CDE官网今日更新：华润双鹤全资子公司北京双鹤润创的1类新药DC7001A胶囊获准开展临床试验。拟用于治疗系统性红斑狼疮（SLE）和皮肤型红斑狼疮（CLE），但不清楚其具体作用靶点和分子机制，华润双鹤也未公开，所以原则上不会是首创，偏me too。从剂型判断，胶囊剂通常对应口服小分子化合物。当前SLE领域的在研小分子主要集中在TLR7/8抑制剂、TYK2抑制剂、IRAK4抑制剂等方向，默克的Enpatoran（TLR7/8抑制剂）已于2026年7月获FDA突破性疗法认定，用于狼疮皮肤表现。该药同时申报SLE和CLE两个适应症。CLE即皮肤型红斑狼疮，约半数SLE患者伴有皮肤表现，也有部分患者仅表现为皮肤受累而无系统症状。双适应症布局意味着研发团队可能观察到该分子在皮肤炎症通路上的活性信号。SLE是当前全球药企布局最密集的自免赛道之一。据统计，全球有超过140款SLE在研疗法，涉及120余家公司，涵盖生物制剂、口服小分子乃至CAR-T细胞治疗。已上市的核心产品包括葛兰素史克旗下BAFF抑制剂贝利尤单抗，据第三方行业报告估算，2025年国内销售额约5.2亿元，市占率约31.4%，居首位。阿斯利康旗下I型干扰素受体（IFNAR-1）拮抗剂阿尼鲁单抗，2025年全球销售额6.86亿美元。及荣昌生物自主研发的BAFF/APRIL双靶点融合蛋白泰它西普，2025年销售额达13.87亿元，并已经拓展至类风湿关节炎、重症肌无力、干燥综合征、IgA肾病等多个适应症。在研后期管线中，罗氏的奥妥珠单抗（CD20单抗）于2026年4月获FDA受理SLE上市申请，PDUFA日期为2026年12月。诺华的Ianalumab（BAFF-R抑制剂）、Biogen的Litifilimab（BDCA2抑制剂）均处于III期阶段。国内企业方面，恒瑞医药、泽璟制药、凌科药业、迪哲医药、康方生物等均有CLE/SLE方向的JAK或TYK2抑制剂在研，诺诚健华的ICP-488（TYK2抑制剂）已于2026年5月完成CLEII期首例患者入组。北京双鹤润创科技有限公司成立于2021年10月12日，法定代表人赵骞，注册资本2亿元人民币，为华润双鹤旗下创新药平台。赵骞，任中国科学院上海有机化学研究所天然产物有机合成重点实验室助理研究员；江苏奥赛康药业有限公司药物研究院手性药物研究所所长助理、药物研究院院长助理、副院长；济川药业集团有限公司药物研究院院长、副总经理。2024年9月辞去济川药业副总经理职务后，于2024年10月25日被华润双鹤董事会聘任为公司总裁。2025年报酬总额113.94万元。该公司另一款新药，DC6001片（青少年黄斑变性），于2026年1月获FDA临床试验默示许可，并获FDA罕见儿科疾病用药（RPDD）和孤儿药（ODD）双认定；2026年3月完成I期临床首例受试者入组。还有一款DC50292A片（晚期实体瘤），目前处于I期临床。从股权结构看，早期公告中双鹤润创曾被表述为全资孙公司，最新公告已统一为全资子公司，推测期间经历了股权架构调整，提升了级别。

2026-08-10

·丁香园皮肤时间

面部红斑、光敏感，是玫瑰痤疮还是 CLE？鉴别要点来了

红斑狼疮具有复杂的临床、生物学及免疫学表现谱，既可为局限于皮肤的皮肤型红斑狼疮（cutaneous lupus erythematosus，CLE），也可作为一种可能危及生命的系统性红斑狼疮（SLE）。约 80% 的 SLE 患者出现皮肤受累，在约 5% 的病例中 CLE 为 SLE 的首发表现。诊断需病理+免疫组化，鉴别玫瑰痤疮、皮肌炎等模仿者，本文根据最新综述[1]，总结 CLE 领域的新进展，涵盖发病机制、分类、诊断、预后及治疗策略及新兴疗法。发病机制 CLE 的发病机制涉及环境诱因、遗传易感性以及先天性与适应性免疫失调之间复杂的相互作用。紫外线辐射是关键环境因素，可诱导角质形成细胞死亡、释放核抗原，促进局部炎症及免疫激活，使免疫复合物形成并沉积于真表皮交界处。自身抗体在 SLE 发病机制中发挥重要作用，并且常早于临床发病出现。在 CLE 中，有研究提出 UV 辐射可诱导角质形成细胞死亡及胞内抗原外露，随后被循环中的自身抗体识别，形成的免疫复合物进一步刺激浆细胞样树突细胞（pDC）产生 I型 IFN，尤其是 IFN-α。分类系统 CLE 有多种分类体系，其中应用最广泛的是 Gilliam 和 Sontheimer 在 1981 年提出的临床病理分类，该体系将红斑狼疮的皮肤表现分为特异性和非特异性皮损。特异性皮损即 CLE，病理特征为界面皮炎，并进一步分为三大临床亚型：急性 CLE（ACLE）、亚急性 CLE（SCLE）及慢性 CLE（CCLE）。 CCLE 包括盘状红斑狼疮（DLE，最常见亚型）、冻疮样狼疮、狼疮性脂膜炎及肿胀性狼疮（tumid lupus）（见图 1）。图 1 . CLE 不同亚型的典型表现（图源参考文献） Kuhn 等在 2009 年提出将肿胀性狼疮单独归类为中间型 CLE（ICLE），原因是它与 SLE 关联较少且具有显著光敏感性。 Dan Lipsker 提出了另一种基于临床病理对应关系的分类方法。他强调，肿胀性狼疮及近半数狼疮性脂膜炎病例不存在典型的界面皮炎，故建议根据皮肤受累层次对 CLE 进行分类： ①表皮－真皮型：ACLE、SCLE、DLE、水疱性狼疮； ②真皮型：肿胀性狼疮、Jessner 淋巴细胞浸润症、丘疹结节性黏蛋白沉积症、REM 综合征； ③皮下脂肪型：狼疮性脂膜炎。他还指出，疾病早期皮损往往难以准确分类，这一问题在临床实践中十分常见，故提出了未定类 CLE 的概念。 LE 非特异性皮损则分为血管性与非血管性表现。需要注意的是，CLE 或 SLE 患者的肢端紫癜很常见，常被过度诊断为狼疮性血管炎，在临床病理评估后，90% 以上的病例最终被诊断为 CLE（主要为 DLE 或冻疮样狼疮），4% 为抗磷脂综合征相关闭塞性血管病，仅 4% 真正属于狼疮性血管炎。诊疗流程在 SLE 背景下，CLE 的诊断有时仅凭临床特征即可完成，但多数情况下仍需皮肤病理证实。CLE 的典型病理表现包括不同程度的界面皮炎，其特征为基底层变性、角质形成细胞凋亡及空泡样变，同时伴有血管及附属器周围淋巴细胞浸润。PAS、CD123、阿新蓝及 MxA（黏病毒抗性蛋白 A）等免疫组化染色可帮助排除模仿疾病。许多常见及罕见皮肤病均可模仿 CLE：面部蝶形红斑及光敏感需与玫瑰痤疮鉴别，后者常伴脓疱、毛细血管扩张，但部分患者 ANA 及 DIF 亦可阳性，因此必要时需皮肤活检； DLE 需与银屑病、扁平苔藓、脂溢性皮炎、皮肌炎及皮肤淋巴瘤等鉴别；冻疮样狼疮、狼疮性脂膜炎等特殊亚型，还需与血管炎、结节性红斑、淋巴细胞浸润性疾病及感染性疾病鉴别。此外，应进一步评估是否合并 SLE、抗磷脂综合征及其他自身免疫病，以避免漏诊系统病变或误诊为单纯皮肤病。进展风险与 SCLE 及 CCLE 相比，ACLE 患者合并 SLE 的比例更高（见图 2）。CLE 进展为 SLE 的风险范围为 0%～42%，不同研究之间差异显著。例如，瑞典全国队列研究显示，24% 的患者在 CLE 确诊时已合并 SLE，而 18% 的患者在 3 年内进展为 SLE；另一项多中心研究纳入 286 例孤立性 CLE 患者，结果显示 12.6% 的患者进展为 SLE，而仅 5.6% 出现严重 SLE 表现。图 2 .由 CLE 进展为 SLE 的风险示意图（图源参考文献）治疗策略目前 CLE 循证医学证据仍较有限，现有指南及治疗综述多基于专家意见，先看表格。表 1 皮肤型红斑狼疮治疗药物一览表说明：系统性糖皮质激素（泼尼松 0.5-1 mg/kg/d，疗程 ≤ 2-4 周）仅用于严重或广泛 CLE，不推荐长期使用。生物制剂目前仅获批用于合并 SLE 的患者，单纯的 CLE 患者使用属超说明书。表格中的数据均来自原文引用的研究或共识，供临床参考。一线治疗所有患者均推荐采取预防措施，包括：戒烟、严格防晒。对于 SCLE 患者应评估药物诱导性狼疮的可能。近年来，除普鲁卡因胺、特比萘芬及肼屈嗪等经典药物外，质子泵抑制剂（PPI）及抗 TNF 药物也逐渐成为 SCLE 常见诱因。建议补充维生素 D，因为其在健康志愿者中已被证实具有光保护作用。此外，CLE 患者更易存在维生素 D 缺乏，补充维生素 D 与 CLE 改善相关。一线治疗包括抗疟药（主要为羟氯喹）联合外用治疗。小型随机对照试验证实，外用糖皮质激素及外用钙调磷酸酶抑制剂均对 CLE 有效。近期系统综述显示，0.05% 氯倍他索、4% 及 2% 烟酰胺以及 0.1% 他克莫司均优于安慰剂。对于轻度 CLE，推荐仅采用外用治疗作为一线方案，但也有研究显示，早期使用羟氯喹可降低进展为 SLE 的风险。系统性糖皮质激素适用于严重或广泛 CLE，但在 CLE 中的疗效尚缺乏明确证据。推荐剂量为 0.5~1 mg/kg.d，疗程不超过 2~4 周。对于未合并 SLE 的患者，不推荐长期使用糖皮质激素。若抗疟药疗效欠佳，可考虑优化方案，例如，将羟氯喹更换为氯喹；在羟氯喹或氯喹基础上联合阿的平（quinacrine）；根据血药浓度调整羟氯喹剂量。二线及三线治疗不同指南对于二、三线治疗推荐略有差异，尤其取决于 CLE 是否合并 SLE。需要强调的是，目前生物制剂仅获批用于合并 SLE 患者。使用免疫抑制剂时，应根据当前风湿免疫疾病免疫抑制患者指南及时更新。甲氨蝶呤被所有 CLE 指南推荐为二线药物，有研究显示，甲氨喋呤治疗 DLE 和 SCLE 的 CLASI-50 应答率分别为 46% 和 72%；吗替麦考酚酯在所有 CLE 亚型中的 CLASI-50 应答率达到 70%。甲氨蝶呤推荐剂量为每周 15~25 mg，口服或皮下注射；口服吗替麦考酚酯剂量为 2000~3000 mg/d。沙利度胺在 CLE 中被推荐为二线或三线药物，起效快，剂量通常为 50~100 mg/d，应注意其不良反应风险如致畸性、周围神经病变及血栓栓塞，并以最小有效剂量用药。来那度胺 5 mg/d 显示出类似疗效，CLASI-50 应答率可达 80%～88%。阿维 A 50 mg/d 与羟氯喹 400 mg/d 的疗效相似，但羟氯喹耐受性更佳。异维 A 酸及阿利维 A 酸也在小型病例系列中显示出对 CLE 有效。在指南中，维 A 酸类主要推荐用于角化过度型 DLE。氨苯砜被推荐为 CLE 的二线或三线药物。值得注意的是，它是目前唯一被推荐可在妊娠期或哺乳期使用的二线药物，推荐剂量为 50~150 mg/d。生物制剂利妥昔单抗常作为重度或难治性 SLE 患者的二线或三线治疗，但对 CLE 的治疗价值有限。贝利尤单抗可降低 SLE 整体疾病活动度并延长复发时间，还改善狼疮性肾炎。但该药对难治性 CLE 的疗效数据仍有限。阿尼鲁单抗于 2022 年在欧洲获批用于 SLE，多项真实世界研究报道，该药对合并 SLE 的难治性 CLE 具有快速疗效，覆盖所有 CLE 亚型，包括冻疮样狼疮及狼疮性脂膜炎等罕见亚型。新兴治疗近年来，CLE 新型治疗药物的研发迅速扩展。目前已有多项专门针对 CLE 的 Ⅲ 期临床试验正在进行，包括： I 型干扰素通路相关治疗：阿尼鲁单抗皮下注射方案（150 mg，每周一次）Ⅲ 期研究目前正在伴有或不伴 SLE 的 CLE 患者中开展；Dazukibart 是一种中和 IFN-β 的单克隆抗体，在皮肌炎中已显示良好前景，目前正在 CLE 患者开展 Ⅱ 期临床试验。多种靶向浆细胞样树突细胞（pDC）的药物已显示出令人鼓舞的结果，包括 litifilimab（抗BDCA2抗体）和 daxdilimab（抗ILT7抗体）。在 litifilimab 的 Ⅱ 期研究中，第 16 周时治疗组 43.6% 的患者达到 CLASI-50，而安慰剂组仅为 22%。daxdilimab 的 I 期研究显示，该药可改善 CLASI-A 评分。 TLR7/8 抑制剂 Afimetoran和enpatoran 是可逆性抑制 TLR7/8 信号通路的小分子药物。Enpatoran 在 Ⅱ 期研究中显示出良好前景，治疗组中最高 91.3% 的患者在第 16 周达到 CLASI-50。Afimetoran 在 I 期研究中耐受性良好，8 例患者中有 5 例在第 16 周时 CLASI-A 改善超过 50%。 TYK2 抑制剂 deucravacitinib（已获批用于银屑病）在 Ⅱ 期 CLE 研究中显示出较好疗效：第 16 周时 54.5% 的患者达到 CLASI-50，而安慰剂组仅为 19%。局部 JAK 抑制剂也正在研究中，例如芦可替尼、迪高替尼乳膏。小结： CLE 的临床表现多样且有时较为复杂，因此在诊断过程中，即使患者已明确存在 CLE 或 SLE，也应始终谨慎排除 CLE 模拟疾病。 CLE 的管理需要综合性策略，包括：一般预防措施、外用治疗、抗疟药、系统性免疫抑制剂、新兴生物制剂。治疗方案应根据CLE亚型、疾病严重程度、瘢痕风险以及是否存在系统受累进行个体化制定。特别说明 | 本文仅供医疗卫生等专业人士阅读参考文献： [1]Chasset F, Teboul A. Update on cutaneous lupus erythematosus pathogenesis, diagnosis and management. J Eur Acad Dermatol Venereol, 2026, 40(5):782-800. 投稿：wudan1@dxy.cn 题图来源：参考文献

临床研究多肽偶联药物

100 项与利替非利单抗相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
皮肤红斑狼疮	临床3期	美国	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	中国	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	日本	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	阿根廷	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	比利时	Biogen Idec Research Ltd.	2023-10-03
皮肤红斑狼疮	临床3期	巴西	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	保加利亚	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	加拿大	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	智利	Biogen, Inc.	2023-10-03
皮肤红斑狼疮	临床3期	哥伦比亚	Biogen, Inc.	2023-10-03

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02847598 (LILAC \| LILAC study, CTgov)	临床2期	皮肤红斑狼疮 \| 系统性红斑狼疮 \| 盘状红斑狼疮	264	Placebo (Part A: Placebo)	獵醖憲窪齋觸夢鹹顧糧(鹽願製鹽廠壓淵鹽壓鹽) = 蓋繭淵簾築齋網構觸憲鏇製鹽築夢廠窪顧鏇齋 (鬱夢顧網衊糧壓齋獵鹽, 10.3) 更多	-	2023-05-15
				BIIB059 (litifilimab) (Part A: BIIB059 450 mg)	獵醖憲窪齋觸夢鹹顧糧(鹽願製鹽廠壓淵鹽壓鹽) = 繭淵鑰願願淵壓製壓遞鏇製鹽築夢廠窪顧鏇齋 (鬱夢顧網衊糧壓齋獵鹽, 8.7) 更多
NCT02847598 (LILAC, Pubmed \| N Engl J Med)	临床2期	系统性红斑狼疮 BDCA2	132	Litifilimab 450 mg	鏇醖鏇構鏇鏇遞餘壓淵(鬱繭膚範築窪膚範憲製): P-Value = 0.04 更多	积极	2022-09-08
				Placebo
NCT02847598 (LILAC, Pubmed \| N Engl J Med)	临床2期	皮肤红斑狼疮	132	Litifilimab 50 mg	鬱鑰製鹹糧鏇艱範糧願(鹹餘範鬱遞膚襯範顧鏇) = Litifilimab was associated with one case of herpes zoster infection 積願醖窪範繭觸願願製 (觸願餘鏇衊壓齋廠壓簾 ) 更多	积极	2022-07-28
				Litifilimab 150 mg
NCT02847598 (LILAC, EULAR2022)	临床2期	系统性红斑狼疮 anti-nuclear antibodies \| anti-double-stranded DNA antibodies	-	BIIB059 450 mg	醖糧鏇蓋鹹衊選糧淵範(壓壓淵夢遞蓋艱顧壓夢) = 觸構鑰觸憲構選遞製鹹窪淵窪鑰構鬱夢蓋鏇構 (醖積糧構夢餘範壓鬱夢 ) 更多	积极	2022-06-01
				Placebo	醖糧鏇蓋鹹衊選糧淵範(壓壓淵夢遞蓋艱顧壓夢) = 淵選廠鏇齋蓋齋淵築鹹窪淵窪鑰構鬱夢蓋鏇構 (醖積糧構夢餘範壓鬱夢 ) 更多
NCT02847598 (LILAC study, EULAR2022)	临床2期	皮肤红斑狼疮 BDCA2	-	BIIB059	醖築窪鬱衊鹽壓鏇廠窪(鏇廠製蓋襯淵選餘鹹壓) = 醖衊築顧簾衊願衊襯製憲糧衊築鏇網憲襯糧鏇 (築廠憲壓廠淵願網襯鑰 ) 更多	积极	2022-06-01
NCT02847598 (LILAC, ACR2020) 人工标引	临床2期	系统性红斑狼疮	120	BIIB059	築繭襯鑰遞願鑰艱蓋構(蓋鹹獵網選網鏇夢鑰簾) = 鹽蓋鹽鑰獵糧積觸衊窪夢簾選餘簾餘窪鬱鏇鑰 (糧獵繭範憲鏇壓鹽構廠, 1.2) 更多	积极	2020-11-07
				Placebo	築繭襯鑰遞願鑰艱蓋構(蓋鹹獵網選網鏇夢鑰簾) = 願顧艱艱壓觸艱鏇範鹽夢簾選餘簾餘窪鬱鏇鑰 (糧獵繭範憲鏇壓鹽構廠, 1.3) 更多
NCT02847598 (LILAC, EULAR2020)	临床2期	皮肤红斑狼疮	132	BIIB059 50 mg	窪範鹹鏇築窪廠鑰壓窪(糧襯憲襯夢糧獵壓顧鹽) = 62 (62.6%) 80 (60.6%) 顧鏇艱齋繭觸鏇鹽廠選 (構鑰壓鹽衊壓窪壓窪獵 ) 更多	积极	2020-06-03
				BIIB059 150 mg
NCT02847598 (Pubmed \| J Pharmacokinet Pharmacodyn)	临床2期	皮肤红斑狼疮	264	BIIB059	糧構遞範構觸夢築範壓(簾鏇憲簾觸夢獵鏇餘鑰) = 顧壓艱鹹襯醖窪築選築簾願選廠簾糧觸觸鹽襯 (網鬱築鏇廠醖選膚膚餘 ) 更多	-	2020-06-01
NCT02106897 (Pubmed \| J Clin Invest) 人工标引	临床1期	湿疹 \| 系统性红斑狼疮	54	BIIB059	觸膚製艱築鹹膚膚襯餘(蓋構壓窪餘製鹹餘製範) = 繭積遞築製蓋夢衊獵遞構簾網夢壓積觸選鹽鹹 (餘獵製選繭繭壓選鏇鹹 ) 更多	积极	2019-03-01
				Placebo	觸膚製艱築鹹膚膚襯餘(蓋構壓窪餘製鹹餘製範) = 繭積鬱糧觸鏇糧襯夢繭構簾網夢壓積觸選鹽鹹 (餘獵製選繭繭壓選鏇鹹 ) 更多
NCT02106897 (EULAR2018)	临床1期	BDCA2 on pDC	-	BIIB059 20 mg/kg IV	壓網憲糧鹽蓋衊願餘齋(鏇願廠觸糧鹽艱廠壓築) = 積壓艱襯繭獵鹽網齋鬱襯網鹽夢艱餘糧鑰觸選 (選鑰鏇夢壓網壓製積繭 ) 更多	-	2018-06-13
				BIIB059 20, 50 or 150 mg SC	夢遞餘艱蓋餘衊壓網衊(鹽積鬱鏇觸鹹壓衊膚齋) = 衊衊鏇餘鑰夢鏇顧願築網衊構糧鏇繭鬱網鬱簾 (鏇淵簾積鏇艱顧築築鏇 ) 更多