Ofatumumab

The approval introduces the first and only anti-CD20 monoclonal antibody shown to improve complete renal response in lupus nephritis, offering a new treatment option for patients and potentially delaying or preventing end-stage kidney disease. 1,2,3 MISSISSAUGA, ON , Jan. 26, 2026 /CNW/ - Hoffmann-La Roche Limited (Roche Canada) is pleased to announce that on January 22, 2026, Health Canada has approved Gazyva® (obinutuzumab) for the treatment of adult patients with active lupus nephritis who are receiving standard therapy. Following four initial doses in the first year, Gazyva can be administered twice yearly, offering an effective and potentially more convenient treatment option than traditional targeted therapies. 3 Health Canada authorizes Gazyva® (obinutuzumab) for adults with active lupus nephritis "Roche Canada is committed to bringing the best innovation in healthcare to Canadians when they need it most. This milestone for Gazyva is a testament to that vision," said Dr. Daniel Edgcumbe, Vice-President, Medical and Regulatory Affairs, Roche Canada. "For Canadians facing lupus nephritis, a disease with no current cure, this represents our ongoing commitment to providing new therapeutic options for lupus nephritis patients." In Canada, lupus affects approximately 1 in 1,000 people. 4 Among those with lupus, nearly 40% develop lupus nephritis, a kidney-specific form of systemic lupus erythematosus (SLE) 5 . SLE is a broader autoimmune disease that can affect various organs, such as the skin, joints, and blood system. Lupus nephritis occurs when the immune system mistakenly attacks the kidneys, potentially leading to impaired kidney function or even kidney failure. "Lupus nephritis is one of the most frequent, severe, and debilitating complications of systemic lupus erythematosus, and treatment options are unfortunately limited," said Dr. Ann Clarke, Professor in the Division of Rheumatology, Department of Medicine, Cumming School of Medicine, University of Calgary. "Health Canada's approval of Gazyva represents a significant advancement in lupus treatment, offering renewed hope to those living with lupus nephritis by improving kidney outcomes and long-term overall health." Health Canada's authorization of Gazyva is based on results from the Phase II NOBILITY and phase III REGENCY studies. In REGENCY, data showed that nearly half of the participants (46.4%) on Gazyva in combination with standard therapy achieved a complete renal response compared to 33.1% on standard therapy alone. That means that adding Gazyva to the current standard of care treatment was more effective than the standard of care treatment alone. Data showed a statistically significant and clinically meaningful increase in the proportion of patients who achieved complete renal response with reduced corticosteroid use and an improvement in proteinuric response, all signalling improved disease control. 2 The safety pro Gazyva was consistent with the well-characterised pro in its haematology-oncology indications. 3 "Lupus nephritis is a complex and unpredictable disease that places a significant burden on patients and families," said Leanne Mielczarek, CEO, Lupus Canada. "Ongoing symptoms and disease flares affect not only physical health but also mental well-being, work, and daily life. Gazyva represents an important new treatment option for Canadians living with lupus nephritis, and Health Canada's approval expands access to much-needed evidence-based therapies for patients and the clinicians who care for them." Roche Canada is committed to working with the provincial and territorial jurisdictions to make Gazyva available as soon as possible through public and private drug plans for the patients who need it. About Lupus Nephritis Lupus nephritis is a potentially life-threatening manifestation of systemic lupus erythematosus, an autoimmune disease that commonly affects the kidneys. 6 Lupus nephritis is characterised by an irreversible loss of nephrons, the filtering structures of the kidneys. Periods of intense disease activity, known as flares, can speed up the loss of nephrons and, if left unchecked, may lead to a progressive loss of kidney function. Even with the latest treatments, up to a third of people will progress to end-stage kidney disease, where dialysis or transplant are the only options and life expectancy and quality of life are substantially reduced. 7 Lupus nephritis affects more than 1.7 million people worldwide – predominantly women, mostly of colour and usually of childbearing age. 8 Currently, there is no cure. 6 About Gazyva Gazyva (obinutuzumab) is a Type II engineered humanised monoclonal antibody designed to attach to CD20, a protein found on certain types of B cells. 9 In lupus nephritis, disease-causing B cells drive persistent inflammation that damages the kidneys and reduces their ability to function properly. 10 Data suggests that Gazyva depletes disease-causing B cells, helping to limit further damage to the kidneys and potentially preventing or delaying progression to end-stage kidney disease. 2 Gazyva is approved for adults with lupus nephritis in Canada, the United States and European Union and in over 100 countries for various types of haematological cancers. About the REGENCY Study REGENCY [ NCT04221477 ] is a phase III, randomised, double-blind, placebo-controlled, multicentre study investigating the efficacy and safety of Gazyva (obinutuzumab) plus standard therapy (mycophenolate mofetil and glucocorticoids) in people with active/chronic International Society of Nephrology/Renal Pathology Society 2003 proliferative Class III or IV lupus nephritis, with or without Class V. The study enrolled 271 people, who were randomised 1:1 to receive either Gazyva plus standard therapy or placebo plus standard therapy. The study population was representative of the real-world population of people with lupus nephritis. About Roche Canada At Roche Canada, patients and science are at the heart of everything we do. Our passion for science and our commitment to relentlessly pursuing the impossible for patients have made us one of the world's leading pharmaceutical, in-vitro diagnostics, and diabetes care management companies. With our combined strength in diagnostics and pharmaceuticals, we're driving healthcare forward, while ensuring we deliver meaningful benefits for patients and a sustainable healthcare system. Because we're committed to making quality healthcare accessible to everyone. And we're adding our expertise in new areas, such as artificial intelligence, real world data collection and analysis and collaborating with many different sectors and industries. Having the courage to reinvent ourselves and question the status quo is what patients and the healthcare system expect from Roche – and our commitment is as strong today as it was on the first day of our Canadian journey in 1931. Today, Roche Canada employs almost 2,000 people across the country through its Pharmaceuticals division in Mississauga, Ontario as well as its Diagnostics division in Laval, Québec. For more information, please visit or follow Roche Canada on LinkedIn. All trademarks used or mentioned are the property of its respective owners. References 1. Furie RA, et al. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022 Jan;81(1):100-07. 2. Furie RA, et al. Efficacy and safety of obinutuzumab in active lupus nephritis. N Engl J Med. 2025 Feb;392:1471-83. 3. Gazyva Product Monograph, January 22, 2026 4. Lupus Canada; [cited 2026 January 7]. Available from: 5. Hanly JG,et al. The frequency and outcome of lupus nephritis: results from an international inception cohort study. Rheumatology (Oxford). 2016 Feb;55(2):252-62. 6. Hocaoglu M et al. Incidence, prevalence, and mortality of lupus nephritis: a population-based study over four decades using the Lupus Midwest Network. Arthritis & Rheumatol 2023 Apr;75(4):567-573. 7. Mok C, et al. Treatment of lupus nephritis: consensus evidence and perspectives. Nat Rev Rheumatol. 2023 Apr;19(4):227-38. 8. Anders HJ et al. Lupus nephritis. Nat Rev Dis Primers. 2020 Jan 23;6(1):7. 9. Herter S, et al. Preclinical activity of the type II CD20 antibody GA101 (obinutuzumab) compared with rituximab and ofatumumab in vitro and in xenograft models. Mol Cancer Ther. 2013 Oct;12(10):2031-42. 10. Atisha-Fregoso Y, et al. Meant to B: B cells as a therapeutic target in systemic lupus erythematosus. J Clin Investig. 2021 Jun 15;131(12):e149095. SOURCE Hoffmann-La Roche Limited (Roche Canada)

肺纤维化是一组以肺间质纤维组织异常增生、肺泡结构破坏为核心特征的进行性间质性肺疾病，其病理进程不可逆、预后差，临床亟待有效的靶向干预手段。利妥昔单抗作为一种人鼠嵌合型抗CD20单克隆抗体，最初获批用于B细胞淋巴瘤的治疗，后因对自身免疫性疾病的显著疗效被逐步拓展至间质性肺疾病领域。关于其是否能逆转肺纤维化，目前基础研究与临床证据均显示其具有潜在的干预价值，但尚未达到“逆转”的临床效果，更多体现为延缓疾病进展、改善肺功能及临床症状，且其应用具有严格的适应症与人群选择性。本文结合最新基础研究、临床研究及指南推荐，对利妥昔单抗在肺纤维化中的作用机制、临床证据及应用现状进行系统解析，为临床实践提供参考。一、利妥昔单抗干预肺纤维化的核心作用机制肺纤维化的发病机制复杂，涉及免疫紊乱、上皮细胞损伤、成纤维细胞异常活化、细胞外基质过度沉积等多个环节，而B细胞介导的体液免疫紊乱与免疫复合物沉积，是自身免疫相关肺纤维化的关键驱动因素，这也是利妥昔单抗发挥作用的核心靶点。利妥昔单抗可特异性结合B细胞表面的CD20抗原，通过抗体依赖性细胞介导的细胞毒性作用（ADCC）、补体依赖性细胞毒性作用（CDC）及诱导B细胞凋亡等途径，实现外周血中B细胞的耗竭，从而阻断其异常的免疫活化。具体而言，其对肺纤维化的干预作用体现在三方面：一是清除致病性B细胞，减少抗核抗体、抗肺基底膜抗体等自身抗体的产生，避免免疫复合物在肺间质沉积引发的持续性炎症损伤，阻断“炎症-损伤-修复异常”的恶性循环；二是抑制B细胞分泌的促纤维化细胞因子（如TGF-β、IL-6、IL-13等），直接减弱成纤维细胞的活化与增殖，减少细胞外基质的合成与沉积；三是调节T细胞亚群平衡，降低Th2细胞、Tfh细胞的促纤维化作用，恢复机体对肺组织损伤的正常修复能力。值得注意的是，利妥昔单抗的作用靶点聚焦于免疫介导的肺纤维化环节，对特发性肺纤维化（IPF）等非免疫介导、以上皮细胞损伤和成纤维细胞异常活化为主的肺纤维化，其作用机制缺乏直接靶点，这也是其临床应用存在人群差异的核心原因。二、利妥昔单抗在肺纤维化中的临床证据：延缓进展而非逆转目前关于利妥昔单抗治疗肺纤维化的临床研究，主要集中于结缔组织病相关间质性肺疾病（CTD-ILD），包括系统性硬化症相关间质性肺疾病（SSc-ILD）、干燥综合征相关间质性肺疾病（pSS-ILD）、类风湿关节炎相关间质性肺疾病（RA-ILD）等，少量研究涉及特发性非特异性间质性肺炎（iNSIP），而针对IPF的临床研究均未显示出显著获益，相关证据等级如下：（一）结缔组织病相关间质性肺疾病（CTD-ILD）：明确的病情改善证据CTD-ILD是自身免疫性疾病累及肺部的常见并发症，免疫紊乱是其核心发病机制，也是利妥昔单抗临床应用的主要适应症，多项多中心、随机对照试验（RCT）及真实世界研究证实了其有效性：1. 系统性硬化症相关间质性肺疾病（SSc-ILD）：作为SSc-ILD的二线治疗药物，利妥昔单抗的疗效得到多项研究证实。《新英格兰医学杂志》发表的Scleroderma Lung Study II（SLS II）研究显示，利妥昔单抗治疗SSc-ILD患者52周后，用力肺活量（FVC）较基线的下降幅度显著低于环磷酰胺组，且患者的呼吸困难评分、6分钟步行试验（6MWT）距离均得到显著改善，肺高分辨率CT（HRCT）显示肺间质炎症灶明显吸收，纤维灶进展得到有效遏制。2024年欧洲抗风湿病联盟（EULAR）SSc管理指南明确推荐，利妥昔单抗用于中重度SSc-ILD患者的治疗，尤其是对环磷酰胺不耐受或治疗无效者。2. 其他CTD-ILD：在pSS-ILD、RA-ILD等疾病中，真实世界研究显示，利妥昔单抗可显著降低患者的疾病活动度，减少糖皮质激素及免疫抑制剂的用量，延缓FVC的下降，对合并抗合成酶抗体综合征（ASS）的ILD患者，其改善肺功能的效果更为显著。上述研究均显示，利妥昔单抗可有效减轻肺间质炎症、延缓纤维灶进展、保护肺功能，但尚未观察到肺HRCT中已形成的纤维灶出现吸收、肺泡结构恢复的“逆转”表现，即其无法消除已沉积的细胞外基质和已破坏的肺组织结构。（二）特发性间质性肺炎（IIP）：仅对免疫相关亚型可能获益特发性间质性肺炎中，除IPF外，iNSIP、隐源性机化性肺炎（COP）等亚型存在一定的免疫炎症参与，少量小样本研究显示，利妥昔单抗对糖皮质激素治疗无效的难治性iNSIP患者，可改善其肺功能和临床症状，但缺乏大样本RCT研究证实；而针对IPF的多项临床研究（如RECORD研究）均显示，利妥昔单抗对IPF患者的FVC、肺HRCT及生存率均无显著改善，2025年《特发性肺纤维化诊断和治疗中国指南》明确指出，不推荐利妥昔单抗用于IPF的治疗。（三）总结：临床疗效的核心特征综合现有证据，利妥昔单抗对肺纤维化的临床疗效具有“抗炎有效、抗纤有限，延缓进展、无法逆转”的核心特征：其可有效清除肺间质的免疫炎症，阻断纤维化的进一步发展，保护残存的肺功能，改善患者的生活质量和预后，但对已经形成的肺纤维灶和不可逆的肺泡结构破坏，尚无明确的逆转作用。三、利妥昔单抗在肺纤维化临床应用中的关键问题（一）严格的适应症选择利妥昔单抗并非肺纤维化的广谱治疗药物，其临床应用需严格限定人群：推荐用于中重度CTD-ILD（尤其是SSc-ILD、ASS-ILD），对糖皮质激素或传统免疫抑制剂（环磷酰胺、吗替麦考酚酯）不耐受、治疗无效或疾病持续进展的患者；可尝试用于难治性iNSIP；禁止用于IPF及其他非免疫介导的肺纤维化。（二）给药方案与疗效监测目前临床常用的给药方案为375mg/m²，静脉滴注，每周1次，共4次为1个疗程，后续根据患者的疾病活动度、B细胞恢复情况及肺功能变化，每6~12个月进行维持治疗。疗效监测需结合临床症状（呼吸困难、咳嗽）、肺功能指标（FVC、DLco）、肺HRCT及血清自身抗体、B细胞计数，其中FVC的变化是评估疗效的核心指标，若治疗后FVC下降幅度<10%/年，提示治疗有效。（三）安全性与不良反应管理利妥昔单抗的安全性较好，主要不良反应集中在输液反应（发热、寒战、皮疹）、一过性骨髓抑制、感染风险升高（呼吸道感染、带状疱疹），罕见严重不良反应（进行性多灶性白质脑病、严重感染）。临床应用中，输液前需给予糖皮质激素、抗组胺药物预防输液反应；治疗期间需定期监测血常规、肝肾功能，避免与其他强效免疫抑制剂联用，降低感染风险；对合并肺部感染的患者，需先控制感染再行治疗。（四）联合治疗策略利妥昔单抗在肺纤维化中的应用多为联合治疗，可与低剂量糖皮质激素、抗纤维化药物（如吡非尼酮、尼达尼布）联用：对CTD-ILD患者，联合抗纤维化药物可实现“抗炎+抗纤”的双重作用，更有效地延缓疾病进展；需注意避免与环磷酰胺等强效免疫抑制剂联用，减少骨髓抑制和感染的叠加风险。四、研究展望与未解决的问题尽管利妥昔单抗在免疫介导的肺纤维化中显示出明确的临床价值，但关于其能否实现肺纤维化的“逆转”，仍有诸多问题亟待解决，也是未来研究的核心方向：1. 早期干预的价值：目前临床研究多纳入中重度肺纤维化患者，已形成明显的纤维灶，若在疾病早期（仅存在肺间质炎症、尚未出现显著纤维沉积）使用利妥昔单抗，是否能阻断纤维化的发生，甚至实现炎症灶的完全吸收，仍需大样本、长期随访的RCT研究证实。2. 精准靶向的优化：现有利妥昔单抗为全人鼠嵌合抗体，耗竭所有CD20+B细胞，存在一定的免疫抑制风险，未来研发的靶向致病性B细胞的单克隆抗体（如奥法木单抗、奥妥珠单抗），或可在减少不良反应的同时，提升抗纤维化效果。3. 与抗纤维化药物的协同机制：利妥昔单抗与吡非尼酮、尼达尼布等抗纤维化药物的协同作用机制尚未完全阐明，二者联用的最佳给药时机、剂量配比仍需进一步研究，以实现疗效最大化。4. 生物标志物指导下的精准治疗：目前尚未发现可预测利妥昔单抗治疗肺纤维化疗效的特异性生物标志物，未来需探索血清细胞因子（如TGF-β、IL-6）、microRNA、肺组织活检标志物等，实现患者的分层治疗，提高治疗的有效性和安全性。五、结论利妥昔单抗作为一种靶向B细胞的单克隆抗体，是免疫介导肺纤维化（主要为CTD-ILD）的重要治疗药物，其核心价值在于通过耗竭致病性B细胞、阻断免疫炎症反应，有效减轻肺间质炎症，延缓纤维灶进展，保护肺功能，改善患者的临床症状和预后，但目前尚无充分的基础和临床证据证实其能逆转已形成的肺纤维化，无法消除已沉积的细胞外基质和已破坏的肺泡结构。临床应用中，需严格把握利妥昔单抗的适应症，仅用于免疫介导的肺纤维化，避免用于IPF等非免疫介导亚型；同时需注重给药方案的个体化、疗效的动态监测及不良反应的管理，联合抗纤维化药物实现“抗炎+抗纤”的双重干预。未来随着早期干预研究、精准靶向药物研发及生物标志物探索的深入，利妥昔单抗及其他B细胞靶向药物在肺纤维化中的应用价值或将进一步提升，为实现肺纤维化的“逆转”提供新的可能，但目前仍需以循证医学为基础，规范其临床应用。综上，利妥昔单抗是肺纤维化病情控制的有效手段，但并非“逆转”肺纤维化的突破性药物，其临床应用需理性看待，结合疾病亚型、发病机制及患者个体情况，制定精准的治疗方案。我可以帮你将这篇文献报道精简为适合公众号发布的科普短文，突出核心结论和临床关键要点，需要吗？