Emapalumab-LZSG

Press releases News Image gallery YouTube Subscribe Sobi® (STO: SOBI), today announced its participation at the 65th American Society of Hematology (ASH) Annual Meeting, taking place on 6 – 9 December in Orlando, Florida. At this year’s meeting, Sobi will showcase its commitment to advancing care in haematology with 19 scientific abstracts, including two oral presentations. These feature the most recent clinical data and insights from completed and ongoing studies across Sobi’s innovative portfolio including data from efanesoctocog alfa, pegcetacoplan, avatrombopag, emapalumab, and pacritinib. These presentations underscore Sobi’s mission to deliver life-changing therapies for patients with rare and severe blood disorders. “We will present evidence at ASH from a post hoc analysis demonstrating that pacritinib reduces or stabilises spleen size, improves haematologic parameters, and lessens myelofibrosis symptoms in patients with highrisk disease. These findings matter because they address key drivers of morbidity which affect daytoday functioning and quality of life. The ASH meeting also offers an opportunity to discuss the latest research on emapalumab, efanesoctocog alfa, pegcetacoplan, avatrombopag, as well as loncastuximab tesirine,” said Lydia Abad-Franch, MD, Head of R&D and Medical Affairs, and Chief Medical Officer at Sobi. Summary of full Sobi data to be presented at ASH 2025: Efanesoctocog alfa Clinical outcomes up to four years of once-weekly Efanesoctocog Alfa Prophylaxis in previously treated adults, adolescents, and children with severe Haemophilia A: Interim analysis of the Phase 3 XTEND-ed long-term extension study. Oral Presentation Session Name: 322. Haemophilia A and B: Clinical and epidemiological: Innovations shaping the future of Haemophilia care Date: 7 December 2025 Time: 12:00 PM - 1:30 PM ET Presentation Time: 1:00 PM - 1:15 PM ET Room: OCCC – W304EFGH Publication Number: 539 Understanding unmet needs for people with Haemophilia A receiving factor and non-factor treatments. Poster Presentation Session Name: Poster Session I Date: 6 December 2025 Time: 5:30 PM - 7:30 PM ET Room: OCCC - West Halls B3-B4 Publication Number: 2679 Real-world experience of Efanesoctocog Alfa in Haemophilia A patients in the US: A retrospective analysis. Poster Presentation Session Name: Poster Session I Date: 6 December 2025 Time: 5:30 PM - 7:30 PM ET Room: OCCC - West Halls B3-B4 Publication Number: 1286 Patient characteristics, treatment patterns, and bleeding in people with Haemophilia A without inhibitors initiating Efanesoctocog alfa in the US: An administrative claims analysis. Poster Presentation Session Name: Poster Session I Date: 6 December 2025 Time: 5:30 PM - 7:30 PM ET Room: OCCC - West Halls B3-B4 Publication Number: 1290 Quality of life and functional improvements with Efanesoctocog alfa in patients with moderate to severe Haemophilia A: A real-world survey. Poster Presentation Session name: Poster Session III Date: 8 December 2025 Time: 6:00 PM - 8:00 PM ET Room: OCCC - West Halls B3-B4 Publication Number: 4846 Pegcetacoplan Consistent benefits of Pegcetacoplan treatment in PNH patients with and without a history of Aplastic Anaemia in real world: Analysis of the ongoing COMPLETE Phase 4 observational study. Poster Presentation Session Name: 101. Red Cells and Erythropoiesis, Excluding Iron: Poster I Date: 6 December 2025 Time: 5:30 PM - 7:30 PM ET Room: OCCC - West Halls B3-B4 Early results from the ongoing Pegcetacoplan Silo of the International Paroxysmal Nocturnal Haemoglobinuria Interest Group Registry. Poster Presentation Session Name: 508. Bone Marrow Failure: Acquired: Poster II Date: 7 December 2025 Time: 6:00:00 PM – 6:00:00 PM ET Location: OCCC - West Halls B3-B4 Real-world clinical characteristics and treatment outcomes in PNH patients prescribed Pegcetacoplan: Insights of complement inhibitor-experienced and -naïve patients across Europe, the United States and Canada. Poster Presentation Session Name: 508. Bone Marrow Failure: Acquired: Poster III Date: 8 December 2025 Time: 6:00 PM - 8:00 PM ET Room: OCCC - West Halls B3-B4 Pegcetacoplan - Publication Only Abstracts Real-world effectiveness of Pegcetacoplan in Paroxysmal Nocturnal Haemoglobinuria: A systematic review of clinical and patient-reported outcomes. Publication only - published online on 3 November 2025, at 9:00 AM ET Low risk for Meningococcal and encapsulated bacteria infections with systemically administered Pegcetacoplan in Paroxysmal Nocturnal Haemoglobinuria and C3 Glomerulopathies. Overview of treatment advances with complement Inhibitors in patients with Paroxysmal Nocturnal Haemoglobinuria. Optimising PNH treatment with the complement inhibitor Pegcetacoplan: A case report. User experience with Pegcetacoplan on-body Injector in patients with Paroxysmal Nocturnal Hemoglobinuria. Avatrombopag Real-world treatment patterns and outcomes among patients with immune thrombocytopenia (ITP) who switched treatment from Eltrombopag or Romiplostim to Avatrombopag in the United States: Results from the real-AVA 3.5 study. Poster Presentation Session Name: 905. Outcomes research: Non-malignant conditions excluding Hemoglobinopathies: Poster I Date: 6 December 2025 Time: 5:30 PM - 7:30 PM ET Room: OCCC - West Halls B3-B4 Real-world safety and efficacy of Avatrombopag in adults with Immune Thrombocytopenia: A systematic review and meta-analysis. Global Abstract Session Name: 311. Disorders of platelet number or function: Clinical and epidemiological: Poster I Date: 6 December 2025 Time: 5:30 PM – 7:30 PM ET Room: OCCC – West Halls B3-B4 Patient-reported outcomes of Avatrombopag for Chronic Immune Thrombocytopenia: Interim analysis of the Phase 4 ADOPT Study. Poster Presentation Session Name: 905. Outcomes research: Non-malignant conditions excluding Hemoglobinopathies: Poster III Date: 8 December 2025 Time: 6:00 PM - 8:00 PM ET Room: OCCC - West Halls B3-B4 Emapalumab Use of Emapalumab is associated with rapid and sustained benefits in pHLH subgroups, including CNS involvement and previously untreated patients: Pooled analysis of prospective trials NI-0501-04, NI-050105 and NI-050109. Poster Presentation Session Name: 201. Granulocytes, Monocytes, and Macrophages: Poster II Date: 7 December 2025 Time: 6:00 PM - 8:00 PM ET Room: OCCC - West Halls B3-B4 Emapalumab induces rapid, durable responses and reliable bridging to curative HSCT in patients with primary HLH: Pooled analysis of prospective trials NI-0501-04, NI-0501-05 and NI-0501-09. Poster Presentation Session Name: 201. Granulocytes, Monocytes, and Macrophages: Poster III Date: 8 December 2025 Time: 6:00 PM - 8:00 PM ET Room: OCCC - West Halls B3-B4 Pacritinib Real-world treatment patterns and outcomes in patients with myelofibrosis who presented with thrombocytopenia and anaemia at initiation of Pacritinib treatment. Oral Presentation Session Name: 908. Outcomes Research: Myeloid Malignancies: Real-World Experiences Session date: 7 December 2025 Session time: 4:30 PM - 6:00 PM ET Presentation time: 5:30 PM - 5:45 PM Room: OCCC - W414CD Pacritinib in patients with high-risk myelofibrosis: Outcomes from post-hoc analyses of two Phase 3 studies. Poster Presentation Session Name: 634. Myeloproliferative Syndromes: Clinical and epidemiological: Poster I Date: 6 December 2025 Time: 5:30 PM - 7:30 PM ET Room: OCCC - West Halls B3-B4 Real-world treatment patterns and clinical outcomes in patients with Myelofibrosis treated with Pacritinib (PAC): Results from the MY-PAC Study. Poster Presentation Session Name: 908. Outcomes research: Myeloid Malignancies: Poster II Date: 7 December 2025 Time: 6:00 PM - 8:00 PM ET Room: OCCC - West Halls B3-B4 PROSPERA (ABNL-MARRO 002): A randomised Phase 2 study of Pacritinib vs. Hydroxyurea in patients with Advanced Proliferative Chronic Myelomonocytic Leukaemia (CMML) Poster Presentation Session Name: 637. Myelodysplastic Syndromes: Clinical and epidemiological: Poster II Date: 7 December 2025 Time: 6:00 PM - 8:00 PM ET Room: OCCC - West Halls B3-B4 Treatment patterns and outcomes in patients with myelofibrosis treated with Pacritinib following a switch from Ruxolitinib: The MY-PAC Study. Session Name: 634. Myeloproliferative Syndromes: Clinical and epidemiological: Poster III Date: 8 December 2025 Time: 6:00 PM - 8:00 PM ET Room: OCCC - West Halls B3-B4 Incidence, prevalence, and clinical outcomes of Myelofibrosis with and without Cytopenia in the United States. About ALTUVOCT ® (efanesoctocog alfa) ALTUVOCT® (efanesoctocog alfa) is indicated for the treatment and prophylaxis of bleeding in patients with haemophilia A (HA). ALTUVOCT can be used for all age groups and any disease severity. About the Sobi and Sanofi Collaboration Sobi and Sanofi collaborate on the development and commercialisation of ALTUVOCT® (efanesoctocog alfa), or ALTUVIIIO™ in the US. Sobi has final development and commercialisation rights in the Sobi territory (essentially Europe, North Africa, Russia, and most Middle Eastern markets). Sanofi has final development and commercialisation rights in North America and all other regions in the world excluding the Sobi territory. About Aspaveli®/Empaveli® (pegcetacoplan) Aspaveli/Empaveli (pegcetacoplan) is a targeted C3 and C3b inhibitor designed to regulate excessive activation of the complement cascade, part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Aspaveli/Empaveli is approved for the treatment of adults with paroxysmal nocturnal haemoglobinuria (PNH) in the US, European Union, and other countries globally, and for C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN) in the United States. It is under regulatory review for C3G and primary IC-MPGN in the European Union and other countries globally. About the Sobi and Apellis Collaboration Apellis and Sobi have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-U.S. commercialisation rights for systemic pegcetacoplan, and its opt-in rights for future development programs are unchanged, exercisable at any time prior to commercialisation. Apellis has exclusive U.S. commercialisation rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy. About Doptelet® (avatrombopag) Doptelet (avatrombopag) is indicated for the treatment of primary chronic immune thrombocytopenia (ITP) in adult patients who are refractory to other treatments, and for the treatment of severe thrombocytopenia in adult patients with chronic liver disease (CLD) scheduled to undergo an invasive procedure. Doptelet is also approved for the treatment of chronic ITP in pediatric patients. About Gamifant® (emapalumab-lzsg) Gamifant is an anti-IFNγ antibody that binds free and receptor-bound IFNγ, which when secreted in an uncontrolled manner can cause hyperinflammation. Gamifant is indicated for intravenous infusion over one hour and is FDA approved for the treatment of primary hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS) in Still’s disease. About Vonjo® (pacritinib) Vonjo (pacritinib) is a kinase inhibitor indicated in the United States for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 10⁹/L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. Vonjo is also being investigated for other rare hematologic conditions, including VEXAS syndrome. Sobi® Sobi is a global biopharma company unlocking the potential of breakthrough innovations, transforming everyday life for people living with rare diseases. Sobi has approximately 1,900 employees across Europe, North America, the Middle East, Asia and Australia. In 2024, revenue amounted to SEK 26 billion. Sobi’s share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com and LinkedIn. Contacts For details on how to contact the Sobi Investor Relations Team, please click here. For Sobi Media contacts, click here. To stay up to date with our development, please subscribe to our press releases. Sign up We are a global biopharma company unlocking the potential of breakthrough innovations, transforming everyday life for people living with rare diseases. 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Our values Meet our employees Open positions About At a glance Focus on rare diseases Business strategy Partnership Our commitment Connect Disease awareness Patients as equal contributors Access programmes Clinical Trials Humanitarian programmes Nurture Capability building Trusted education source Patient Engagement in acquisitions Continuous and transparent communication Collaborate Define and deliver on shared objectives Informed decision making (IDM) Patient Engagement and experience data Innovate Innovate disease awareness campaigns Value added services History Board of directors Executive committee Corporate Governance General Meetings Nomination committee Committees Remuneration Auditors Articles of association Therapeutic areas Haematology Haemophilia Immune thrombocytopenia (ITP) Paroxysmal nocturnal haemoglobinuria (PNH) Diffuse large B-cell lymphoma (DLBCL) Immunology Familial Mediterranean fever (FMF) Cryopyrin-associated periodic syndromes (CAPS) Haemophagocytic 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Focus on rare diseases Business strategy Partnership Our commitment Connect Disease awareness Patients as equal contributors Access programmes Clinical Trials Humanitarian programmes Nurture Capability building Trusted education source Patient Engagement in acquisitions Continuous and transparent communication Collaborate Define and deliver on shared objectives Informed decision making (IDM) Patient Engagement and experience data Innovate Innovate disease awareness campaigns Value added services History Board of directors Executive committee Corporate Governance General Meetings Nomination committee Committees Remuneration Auditors Articles of association Partnership Connect Disease awareness Patients as equal contributors Access programmes Clinical Trials Humanitarian programmes Nurture Capability building Trusted education source Patient Engagement in acquisitions Continuous and transparent communication Collaborate Define and deliver on shared objectives Informed decision making (IDM) Patient Engagement and experience data Innovate Innovate disease awareness campaigns Value added services Disease awareness Patients as equal contributors Access programmes Clinical Trials Humanitarian programmes Capability building Trusted education source Patient Engagement in acquisitions Continuous and transparent communication Define and deliver on shared objectives Informed decision making (IDM) Patient Engagement and experience data Innovate disease awareness campaigns Value added services General Meetings Nomination committee Committees Remuneration Auditors Articles of association Haematology Haemophilia Immune thrombocytopenia (ITP) Paroxysmal nocturnal haemoglobinuria (PNH) Diffuse large B-cell lymphoma (DLBCL) Immunology Familial Mediterranean fever (FMF) Cryopyrin-associated periodic syndromes (CAPS) Haemophagocytic lymphohistiocytosis (HLH) Respiratory syncytial virus (RSV) Still’s disease Specialty Care Pipeline Congresses Research & development Investigator sponsored studies Managed Access Programmes Clinical studies and data privacy Medical Grant Haemophilia Immune thrombocytopenia (ITP) Paroxysmal nocturnal haemoglobinuria (PNH) Diffuse large B-cell lymphoma (DLBCL) Familial Mediterranean fever (FMF) Cryopyrin-associated periodic syndromes (CAPS) Haemophagocytic lymphohistiocytosis (HLH) Respiratory syncytial virus (RSV) Still’s disease Investigator sponsored studies Managed Access Programmes Clinical studies and data privacy Sustainability performance Key data Sustainability governance Code of Conduct Policies Governance Commitment to patients Access to treatment Patient centricity Humanitarian aid Act responsibly Caring for employees Environmental footprint Responsible sourcing Compliance Transparency Disclosure of Payments to Healthcare Trade association memberships Supporting patient organisations Key data Code of Conduct Policies Governance Access to treatment Patient centricity Humanitarian aid Caring for employees Environmental footprint Responsible sourcing Compliance Disclosure of Payments to Healthcare Trade association memberships Supporting patient organisations Financial reports Presentations Financial data Calendar Pipeline Share information All trading venues Historical share price look-up Ownership Analyst coverage IR contacts Subscribe MTN-programme Rights issue 2023 All trading venues Historical share price look-up Ownership Analyst coverage Press releases News Image gallery YouTube Subscribe Our values Meet our employees Open positions

斯蒂尔病，包括系统性幼年特发性关节炎（systemic juvenile idiopathic arthritis，sJIA）和成人型斯蒂尔病（adult-onset Still′s disease，AOSD），是一种罕见的自体炎症性疾病，主要特征为高水平的全身性炎症反应，表现为发热、皮疹和关节痛等症状。目前，随着对IL-1、IL-6和IL-18等炎性因子在斯蒂尔病发病机制中作用的进一步了解，sJIA和AOSD的病理机制逐步被揭示，治疗选择也随之扩展。尽管sJIA和AOSD表现为同一疾病的不同临床形式，二者在临床表现上存在一定的年龄相关性，且可能伴随不同的临床进展模式或并发症[如巨噬细胞活化综合征（macrophage activation syndrome，MAS）]，这些因素增加了诊断和管理的挑战。 基于此，EULAR和欧洲儿科风湿病学会（Paediatric Rheumatology European Society，PReS）联合发布了《斯蒂尔病诊治管理推荐意见》，旨在为儿科和成人风湿病学医师提供基于循证证据的诊断和治疗建议。指南从疾病的统一命名、早期诊断策略、最佳治疗方案及并发症管理等方面提出了具体建议。 本文将对2024年EULAR和PReS斯蒂尔病临床实践指南的核心内容进行详细解读，以帮助我国风湿科医师深入理解该指南在诊疗实践中的应用价值。 1　疾病的定义、背景 指南强调，在最初的分类中，AOSD被认为是斯蒂尔病的成人型表现，而sJIA则主要发生在儿童中。实际上，这种区分主要基于医疗分工的组织差异（即16岁作为界限），并未完全反映这2种疾病的实际生物学特征。这一人为划分在接下来的几十年中进一步加剧了sJIA和AOSD在定义、分类标准、临床试验设计和药物批准方面的分歧。随着时间的推移，越来越多的证据表明，sJIA和AOSD在临床表现和基因表达上有着高度的相似性，这支持了它们作为同一种疾病不同表现形式的观点。 从流行病学、临床特征及基因表达分析的现有数据来看，sJIA和AOSD高度相似，支持其统一性。流行病学数据显示，sJIA的发病高峰出现在6岁以下儿童，并在青少年和年轻成人中保持稳定。然而，AOSD通常发生于成人，且其发病年龄多集中在16岁以上。此外，系统性文献回顾显示，除了咽痛和肌痛（幼儿中较难通过病史确认）、体重减轻（儿童中较少见，通常表现为生长停滞）、白细胞计数差异（儿童和成人的正常值不同）以及AA型淀粉样变性（近几十年发病率已显著下降）以外，sJIA和AOSD患者在几乎所有其他临床症状和生物学指标上都表现出类似的情况。在基因表达上，sJIA和AOSD的显著相似性也为两者的统一性提供了有力支持。 尽管如此，年龄差异仍然对疾病的表现、诊断和并发症管理产生显著影响。尤其是18个月以下的婴幼儿更易出现高水平炎症和MAS，这需要临床医生特别关注。儿童和成人在疾病的临床特征、并发症的发生和鉴别诊断上存在差异，因此必须根据不同年龄段的患者特征进行个体化管理。 尽管存在年龄差异和临床表现的多样性，统一命名为"斯蒂尔病"仍具有重要的临床意义。这一命名的采用有助于简化临床理解和研究工作，并且能够更好地统一sJIA和AOSD的诊断和治疗方案。指南制定专家组通过广泛讨论，最终一致同意使用"斯蒂尔病"这一名称，表明了临床实践中的共识和需求，即年龄差异导致了斯蒂尔病在儿童和成人之间的临床表现差异。 2　诊断的挑战性 指南分析了斯蒂尔病在诊断上的挑战性，特别是其临床表现的异质性以及无特异度症状或生物学特征。这种异质性增加了早期识别的难度，因此指南对既往标准（见下文）进行了简化，提出了关键症状的新的早期（时间阈值7 d）诊断标准，以帮助临床医师进行早期识别（ 表1 ）。 斯蒂尔病的主要症状包括发热、皮疹、关节痛或关节炎及急性期反应物高度升高。这些升高的急性期反应物包括CRP、嗜中性粒细胞计数、铁蛋白、血小板、纤维蛋白原和D-二聚体水平。特别是关节表现，关节痛常见，但关节炎通常在疾病发生后约1个月（中位延迟1个月，范围为0至数月）才出现。鉴于有无关节炎患者的免疫病理机制相似，指南建议不将关节炎作为诊断斯蒂尔病的必需条件，以避免潜在的诊断延误和患者不良后果。 在诊断支持方面，尽管现有分类标准并非专为斯蒂尔病设计，但Yamaguchi标准在sJIA和AOSD中均具有高灵敏度。Yamaguchi（sJIA和AOSD）标准和PRINTO（sJIA）标准中均未将关节炎列为诊断必需项。 具体而言，Yamaguchi标准： ①发热≥39 °C，持续超过1周； ②关节炎，持续超过2周； ③典型皮疹（如粉红色斑丘疹，伴随发热尖峰）； ④白细胞计数≥10×109/L，且中性粒细胞≥80%； ⑤咽痛或咽喉痛； ⑥淋巴结肿大和/或脾肿大； ⑦肝功能检测异常（转氨酶升高）； ⑧自身抗体阴性。 最低要求：符合8项中的5项，并且在第1至第4项中至少符合2项。 表现：在成人中，灵敏度为96.3%，特异度为98.2%；若血清铁蛋白增加，灵敏度达到100%，特异度为97.1%；在儿童中，灵敏度为96.4%。 PRINTO（sJIA）标准： ①年龄<18岁； ②发热持续超过2周； ③皮疹； ④关节炎； ⑤淋巴结肿大、肝肿大或脾肿大； ⑥关节痛持续超过2周； ⑦中性粒细胞增多。 最低要求：满足以下任一组合条件即可：①必须全部满足项目1~4，②必须满足项目1和项目2+项目3和4中的任意一项+项目5、6、7中的任意一项。 表现：该标准的灵敏度为98.2%。鉴于上述标准的优异表现，指南指出临床医师可以联合 表1 中诊断标准及上述Yamaguchi标准和PRINTO标准进行辅助诊断。 在生物标志物方面，IL-18、S100蛋白[即S100 A8/A9（也称钙卫蛋白）和S100 A12]的水平在斯蒂尔病患者中显著升高。这些生物标志物升高在斯蒂尔病中显示出较高的灵敏度和特异度，但由于灵敏度和特异度的对照组差异（如不明原因发热、其他自体炎症疾病、感染性疾病等），尚未建立标准化的临床阈值。 斯蒂尔病的诊断需结合一系列临床和生物学特征，且在治疗前需仔细排除其他类似疾病，如感染性疾病、肿瘤及其他免疫介导性疾病，包括单基因炎症性疾病。在成人患者中，VEXAS综合征和克隆性造血应被特别考虑。误诊可能导致不良后果，特别是在存在恶性肿瘤的情况下使用糖皮质激素或免疫抑制剂。 总而言之，指南强调了在斯蒂尔病的诊断中尽早识别和精确分类的必要性。指南的建议强调了标准化诊断指标、生物标志物研究及系统性鉴别诊断的重要性，以便更好地优化患者管理。 3　治疗 3.1　治疗目标 指南提出了2个主要的治疗目标： ①无临床活动：作为即时测量的静态指标，无临床活动定义为无任何斯蒂尔病相关表现，且急性期反应物（如ESR或CRP）均正常。若多次检测急性期反应物，所有结果必须正常，除非存在其他解释异常值的因素（例如贫血导致的ESR升高）。指南还建议纳入医生对疾病活动的主观整体评估，为了界定疾病非常轻微或接近无临床活动，建议在0~100分制视觉模拟疼痛评分中≤10，而在0~10分制中<1，以提高指标的灵敏度。 ②缓解：是一个时间依赖的综合性指标，定义为≥6个月的无临床活动状态，无论是否接受治疗。因此，缓解可以分为治疗期缓解和无药物缓解（即停药后缓解）。 指南还提出，应采用分步的目标导向治疗策略，依据患者的疾病活动性动态调整治疗。这一方法在斯蒂尔病的管理中尤为重要，因为该病的病程伴有急性加重，且可能导致危及生命的并发症。指南强调，特别在治疗初期需密切监测发热、关节活动情况、CRP水平及医生或患者的总体评估，以确保病情得到有效控制。见 表2 。 关于疾病活动性的量化评估，指南指出，目前已有多种评分方法应用于斯蒂尔病的研究中。例如，sJIA疾病活动评分和修订版Pouchot评分较适合斯蒂尔病患者，因为其涵盖了疾病的多种表现。不过，指南指出，目前尚缺乏支持单一工具的足够证据，因此尚未推荐唯一的活动性评分工具。 基于德国和北美儿科风湿病学专家提出的现有建议，指南制定了4个阶段性治疗目标，分别设在第7天、第4周、第3个月和第6个月，旨在为新诊断患者和无药物缓解期复发患者的治疗管理中提供临床指导。不同于复合的疾病临床活动性评分，这些目标基于简单且易于操作的临床标准，有助于在病程的不同阶段实现对患者病情的合理控制。指南特别指出，IL-6是刺激CRP生成的重要因子之一，使用IL-6抑制剂[如托珠单抗（tocilizumab）]后，即使患者体内有潜在的炎症或感染反应，CRP水平可能也无法如预期般升高或呈现轻微的变化。这会导致CRP水平的假性偏低，从而掩盖实际的炎症状态，使得CRP作为炎症标志物的可靠性受到影响。这种情况下，临床医师可能需要依赖其他指标（如ESR、WBC）或综合其他症状和体征来评估患者的真实炎症状态，以避免对病情判断的偏差。可能会对CRP升高的解读产生影响，应予以注意。此外，指南还设定了激素在3个月时的目标剂量，成人和儿童分别为0.1 mg·kg-1·d-1和0.2 mg·kg-1·d-1，以实现持续的疾病控制，同时确保治疗的安全性。 3.2　治疗方案 见 表3 。指南强调了IL-1[如阿那白滞素（anakinra）、卡那单抗（canakinumab）和利纳西普（rilonacept）]和IL-6抑制剂在斯蒂尔病治疗中的关键作用，尤其是在减少激素依赖方面的贡献。IL-1和IL-6抑制剂的引入显著改变了疾病的治疗模式，使得在多数情况下可以显著减少甚至完全避免激素的使用。同时，指南也认可糖皮质激素在斯蒂尔病管理中的疗效。尽管证据等级较低，但数据显示高剂量激素（即≥1 mg·kg-1·d-1的泼尼松等效剂量）在疾病初期，特别是在严重症状、MAS风险或严重心包炎情况下更为有效。然而，长期使用激素常会引起严重不良反应，包括儿童的生长停滞和骨矿化障碍，以及成人的代谢综合征等。因此，指南强调在整个治疗过程中应尽量避免依赖激素，如果患者表现出激素依赖性，应优先考虑增加其他治疗以实现糖皮质无激素控制的目标。 尽管针对sJIA或AOSD的IL-1和IL-6抑制剂的随机对照试验数量有限，但大量现实数据支持其在控制系统性和关节表现方面的有效性，显著减少糖皮质激素的使用。根据现有数据，使用IL-6抑制剂时，严重不良事件（特别是感染）的发生率比使用IL-1抑制剂时更高。在所有IL-1抑制剂中，阿那白滞素表现出相对更高的安全性。此外，阿那白滞素在重症监护病房用于危重脓毒症患者以及在新型冠状病毒肺炎（COVID-19）患者中的使用，均无安全性问题，这进一步支持了其临床应用。 关于传统合成抗风湿药物的使用，支持其在斯蒂尔病疗效的证据较为有限。唯一一项针对sJIA的RCT显示，即使在低应答阈值（30%）下，甲氨蝶呤对比安慰剂也无显著优势。因此，尽管传统药物在有显著关节受累的患者中有部分疗效报告，但当前首选仍为IL-1和IL-6靶向的生物制剂抗风湿药物，传统药物主要用于无法获得生物制剂的地区。 此外，非甾体抗炎药在斯蒂尔病中的疗效无随机对照试验支持，指南建议将其限制为仅用于控制发热和关节痛的症状性治疗，尤其在诊断评估期间。 关于IL-1和IL-6抑制剂的启动时机，尽管目前尚无正式的随机对照试验明确确定最佳启动时机，但现实中的观察性研究和低级别证据表明，早期启动这些抑制剂与短期内良好的治疗效果有关，且能够显著提高患者维持无激素治疗的无临床活动状态的比例。现有数据表明，在症状出现后的3个月内启动IL-1或IL-6抑制剂有助于获得更好的临床结局。此外，与历史数据中延迟开始生物制剂治疗的患者相比，早期使用IL-1或IL-6抑制剂不仅有助于控制疾病活动，还能减少慢性持续病程的发生，这些数据支持了"治疗窗口"的假设，即疾病早期存在一个特定的治疗窗口，早期介入有助于实现最佳的治疗效果。小鼠模型（IL-1受体拮抗蛋白缺乏小鼠）的转化研究进一步验证了这一假设，研究表明早期启动IL-1抑制剂能够有效预防Th17细胞的增生和关节炎的发生，而在疾病晚期则缺乏同样的效果。 应注意斯蒂尔病是一种具有复发潜力的疾病，因此维持缓解是治疗中的重要目标。根据指南，早期启动IL-1或IL-6抑制剂可帮助患者实现较长时间的临床缓解。然而，斯蒂尔病的复发性意味着，除了初期的疾病控制外，还需要在治疗过程中采取长期维持治疗来确保缓解状态的持续。指南重申停用激素是最关键的第1步。对于那些已达到无临床活动且停用激素3~6个月的患者，指南建议可以考虑逐步减少生物制剂的剂量。减量应根据患者的具体情况，按3~6个月的时间步骤进行。减少剂量的方式可以是减少药物的给药量或延长注射间隔，以减少药物浪费和注射次数（ 表4 ）。此时，维持治疗的目标是确保患者能够维持无临床活动状态并尽可能减少药物的不良反应。此外，指南强调，在维持缓解的过程中，定期评估患者的病情是至关重要的。这包括对疾病活动的持续监测，以及根据患者的病情变化及时调整治疗方案。早期识别复发的症状并迅速采取治疗措施，有助于防止病情恶化并缩短复发期。因此，斯蒂尔病的维持治疗不仅需要基于早期治疗的成功，还应当通过个体化管理，在保持临床缓解的同时减少糖皮质激素使用和生物制剂的剂量，从而确保长期的疾病控制和患者的生活质量。 4　并发症的防治 指南强调了斯蒂尔病在并发症管理中的挑战，特别是疾病伴随的严重和潜在危及生命的并发症。指南指出，斯蒂尔病的严重并发症可能会在疾病的各个阶段突发，包括疾病初期、诊断评估期间、接受生物制剂治疗过程中（即使疾病控制良好），以及药物减量期间。因此，指南建议临床医师在整个病程中对患者进行密切监测，并提醒患者在复发或出现新的症状时，及时联系治疗团队。 MAS是斯蒂尔病最常见的并发症，发生率约为15%~20%。在MAS中，先天性免疫的过度反应会迅速释放大量促炎细胞因子，导致急性炎症；而适应性免疫的异常激活则会进一步加剧炎症反应，使得疾病难以控制。这种过度的免疫反应是MAS的特征，造成广泛的组织损伤和全身性炎症。指南指出，尽管没有单一实验室指标可以独立诊断MAS，但早期识别整体过度的炎症模式和监测实验室指标变化是关键。例如，嗜血细胞综合征诊断评分（HScore）评分是一个用于评估和诊断MAS的评分系统，基于多项临床和实验室指标，包括发热、肝脾肿大、血小板计数、三系血细胞减少、甘油三酯水平、血清铁蛋白浓度等。HScore通过分配权重来综合这些指标，评分越高则MAS的可能性越大，有助于早期识别和诊断MAS；而巨噬细胞活化综合征/幼年特发性关节炎评分（MS-core）也用于MAS的筛查，特别是在伴发风湿性疾病的患者中，MS-core包含一些常用的炎症和血液学指标，旨在帮助区分MAS与其他系统性炎症性疾病。该评分也是基于一系列实验室和临床指标，通过统计分析得出诊断MAS的诊断阈值（见 表5 ）。这2种评分方法通过量化实验室和临床异常，使MAS的早期识别更加客观，有助于及早进行干预。指南特别强调，在接受IL-1或IL-6抑制剂治疗的患者中，MAS症状可能被抑制或延迟出现，尤其是发热和铁蛋白升高。 指南建议对所有斯蒂尔病患者常规监测铁蛋白水平，尤其是对MAS高风险患者，需每日或每2日重复测量，以便严密监控病情。尽管高铁蛋白血症可能有其他罕见原因，铁蛋白在MAS诊断中的灵敏度和特异度很高，仍是首选标志物。此外，现代生物标志物（如可溶性IL-2受体、趋化因子配体9、IL-18和活化的CD8 T细胞）在条件允许下也可作为辅助诊断工具。 在MAS的治疗方面，指南建议在启动特异度治疗的同时，积极寻找并控制潜在的触发因素，特别是感染，因控制感染可促进MAS的治疗。高剂量糖皮质激素是MAS的主要治疗手段，通常通过静脉注射甲泼尼龙冲击疗法（15~30 mg·kg-1·d-1，最大剂量1 g/次）。若中枢神经系统受累，应优先选择地塞米松，因为其能更好地穿透血脑屏障。对于初始激素治疗效果不佳或MAS迅速恶化的患者，指南建议联合使用环孢素、阿那白滞素和干扰素-γ中和抗体[依马利尤单抗（emapalumab）]，以提高疗效。 斯蒂尔病相关的肺部疾病是另一种罕见但严重的并发症，表现为间质性炎症性浸润和蛋白沉积。肺部疾病与发病年龄较小、唐氏综合征、反复MAS发作以及高水平血清IL-18有关。指南建议所有斯蒂尔病患者，尤其是高危患者，进行肺部疾病风险评估。肺部疾病临床表现可能在已进入晚期时才出现，因此肺功能测试和高分辨率CT扫描对于早期检测尤为重要。 关于IL-1和IL-6抑制剂的使用，尽管一些假设认为肺部疾病可能与这些药物的过敏反应有关，但指南不建议停用这些抑制剂，原因是大多数肺部疾病患者在停用这些药物后病情未见改善，且停药可能导致MAS严重复发。对高风险患者或已出现肺部疾病的患者，可以考虑使用Janus激酶抑制剂[如芦可替尼（ruxolitinib）、巴瑞替尼（baricitinib）]等T细胞靶向的免疫抑制剂，尽管直接证据尚缺乏。 对于难治性患者，MAS和肺部疾病常在病程早期或治疗过程中出现，对这些患者应设立灵活的中间治疗目标。指南建议在这些情况下考虑使用反复激素冲击、Janus激酶抑制剂、组合传统合成和生物制剂抗风湿药物，以及新型IL-18或干扰素-γ抑制剂等疗法（ 表6 ）。指南还鼓励临床医师通过网络或电话联系斯蒂尔病专家在线或线下会诊，以优化难治性患者的管理并促进新疗法的应用。 5　结语 2024年版《斯蒂尔病诊治管理推荐意见》的发布，为sJIA和AOSD的统一管理提供了循证依据，明确了治疗目标和管理方案。IL-1和IL-6抑制剂的应用为斯蒂尔病的个体化治疗提供了新的路径，特别是在减少糖皮质激素使用和控制疾病活动性方面发挥了重要作用。未来的临床实践需结合患者的个体特点，优化治疗策略，持续关注并发症的早期识别和管理。