Chandrakasan Shanmuganathan, Allen Carl E, Bhatla Deepika, Carter John, Chien May, Cooper Robert, Draper Lauren, Eckstein Olive S, Hanna Rabi, Hays J Allyson, Hermiston Michelle L, Hinson Ashley P, Hobday Patricia M, Isakoff Michael S, Jordan Michael B, Leiding Jennifer W, Modica Renee, Nakano Taizo A, Oladapo Abiola, Patel Sachit A, Pednekar Priti, Riskalla Mona, Sarangi Susmita N, Satwani Prakash, Tandra Anand, Walkovich Kelly J, Yee John D, Zoref-Lorenz Adi, Behrens Edward M
Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia.
Baylor College of Medicine, Houston, Texas.
Arthritis Rheumatol. 2025 Feb;77(2):226-238. doi: 10.1002/art.42985. Epub 2024 Nov 5.
Rheumatologic disease-associated hemophagocytic lymphohistiocytosis (HLH), a rare, life-threatening, systemic hyperinflammatory syndrome, occurs as a complication of underlying rheumatologic disease. Real-world evidence is lacking on emapalumab, a fully human monoclonal antibody that neutralizes the proinflammatory cytokine interferon-γ, approved for treating patients with primary HLH.
REAL-HLH, a retrospective medical chart review study conducted across 33 US hospitals, assessed real-world treatment patterns and outcomes in patients with HLH treated with one or more dose of emapalumab between November 20, 2018, and October 31, 2021. Data are presented for the subset of patients with rheumatologic disease-associated HLH.
Fifteen of 105 patients (14.3%) had rheumatologic disease-associated HLH. Of these, nine (60.0%) had systemic juvenile idiopathic arthritis, and one (6.7%) had adult-onset Still disease. Median (range) age at HLH diagnosis was 5 (0.9-39) years. Most patients (9 of 15; 60.0%) initiated emapalumab in an intensive care unit. Emapalumab was most frequently initiated for treating refractory or recurrent (10 of 15; 66.7%) disease. Most patients received HLH-related therapies before (10 of 15; 66.7%) and concurrently with (15 of 15; 100.0%) emapalumab. Emapalumab-containing regimens stabilized or achieved physician-determined normalization of most laboratory parameters, including absolute neutrophil count and absolute lymphocyte count (13 of 14; 92.9%), chemokine ligand 9 (9 of 11; 81.8%), and platelets and alanine transaminase (11 of 14; 78.6%), and reduced glucocorticoid dose by 80%. Overall survival and 12-month survival probability from emapalumab initiation were 86.7%.
Emapalumab-containing regimens stabilized or normalized most key laboratory parameters, reduced glucocorticoid dose, and were associated with low disease-related mortality, thereby demonstrating potential benefits in patients with rheumatologic disease-associated HLH.
风湿性疾病相关噬血细胞性淋巴组织细胞增生症（HLH）是一种罕见的、危及生命的全身性高炎症综合征，是潜在风湿性疾病的并发症。对于emapalumab（一种获批用于治疗原发性HLH患者的全人源单克隆抗体，可中和促炎细胞因子干扰素-γ），目前缺乏真实世界证据。
REAL-HLH是一项在美国33家医院开展的回顾性病历审查研究，评估了2018年11月20日至2021年10月31日期间接受一剂或多剂emapalumab治疗的HLH患者的真实世界治疗模式和结局。本文给出了风湿性疾病相关HLH患者亚组的数据。
105例患者中有15例（14.3%）患有风湿性疾病相关HLH。其中，9例（60.0%）患有系统性幼年特发性关节炎，1例（6.7%）患有成人斯蒂尔病。HLH诊断时的中位（范围）年龄为5（0.9 - 39）岁。大多数患者（15例中的9例；60.0%）在重症监护病房开始使用emapalumab。emapalumab最常用于治疗难治性或复发性疾病（15例中的10例；66.7%）。大多数患者在使用emapalumab之前（15例中的10例；66.7%）以及同时（15例中的15例；100.0%）接受了与HLH相关的治疗。含emapalumab的治疗方案使大多数实验室参数稳定或达到医生确定的正常水平，包括绝对中性粒细胞计数和绝对淋巴细胞计数（14例中的13例；92.9%）、趋化因子配体9（11例中的9例；81.8%）、血小板和丙氨酸转氨酶（14例中的11例；78.6%），并使糖皮质激素剂量降低了80%。从开始使用emapalumab起的总生存率和12个月生存概率为86.7%。
含emapalumab的治疗方案使大多数关键实验室参数稳定或恢复正常，降低了糖皮质激素剂量，并与低疾病相关死亡率相关，从而证明了其在风湿性疾病相关HLH患者中的潜在益处。
