From the Departments of Neurology (E.H.M., I.P.-F., M.C.-D., A.L.M., T.E.L.), and Medicine (J.A., J.J.P., E.T., B.A., C.A.M., S.K.D., L.C.-S.), Johns Hopkins University School of Medicine, Baltimore, MD; Muscle Disease Unit (I.P.-F., M.C.-D., A.L.M.), Laboratory of Muscle Stem Cells and Gene Regulation, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD; and Faculty of Health Sciences and Faculty of Computer Science (I.P.-F.), Multimedia and Telecommunications, Universitat Oberta de Catalunya, Barcelona, Spain.
Neurology. 2023 Mar 28;100(13):e1406-e1417. doi: 10.1212/WNL.0000000000206777. Epub 2023 Jan 23.
Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in individuals older than 50 years. The disorder is slowly progressive, and although many therapies have been investigated, response has generally been poor. Clinical heterogeneity may influence treatment responsiveness; however, data regarding heterogeneity in IBM are limited and often conflicting. We aim to identify clinically distinct subgroups within a large IBM cohort and prognostic factors for disease progression.
Clinical, histologic, radiologic, and electrophysiologic data were analyzed for all patients with IBM and other forms of myositis enrolled in a longitudinal cohort from The Johns Hopkins Myositis Center from 2003 to 2018. Patients with IBM were included if they met at least one of the following criteria: Griggs possible, European Neuromuscular Centre 2011 probable, or Lloyd-Greenberg data-derived criteria for IBM. Univariate, multivariate, and graphical analyses were used to identify prognostic factors in patients with IBM. Thus, linear and logistic regressions were used to adjust for potential confounding variables. The evolution of creatine kinase and muscle strength was studied using multilevel linear regression models. Nonmodifiable risk factors (sex, race, disease duration, and age at the onset of first symptoms) were used as adjusting covariates for the regression analyses.
Among the 335 patients meeting the inclusion criteria for IBM, 64% were male with an average age of disease onset of 58.7 years and delay to diagnosis of 5.2 years. Initial misdiagnosis (52%) and immunosuppressant treatment (42%) were common. Less than half (43%) of muscle biopsies demonstrated all 3 pathologic hallmarks: endomysial inflammation, mononuclear cell invasion, and rimmed vacuoles. Black patients had significantly weaker arm abductors, hip flexors, and knee flexors compared with non-Black patients. Female patients had stronger finger flexors and knee extensors compared with their male counterparts. Younger age (<50 years) at onset was not associated with increased weakness.
Our study demonstrates that female and Black patients have distinct clinical phenotypes and trajectories within the overarching IBM clinical phenotype. These subgroups may have different responses to therapies, which may influence the design of future clinical trials in IBM.
散发性包涵体肌炎（IBM）是 50 岁以上人群中最常见的获得性肌病。该疾病呈缓慢进展，尽管已经研究了许多治疗方法，但总体反应较差。临床异质性可能影响治疗反应，但关于 IBM 异质性的数据有限且常常相互矛盾。我们旨在确定大型 IBM 队列内具有不同临床特征的亚组以及疾病进展的预后因素。
对 2003 年至 2018 年期间，在约翰霍普金斯肌病中心的一项纵向队列中入组的所有 IBM 及其他类型肌炎患者的临床、组织学、影像学和电生理学数据进行了分析。如果患者符合以下标准中的至少一项，则被纳入 IBM 患者：Griggs 可能、欧洲神经肌肉中心 2011 年可能、或 Lloyd-Greenberg 数据衍生的 IBM 标准。采用单变量、多变量和图形分析来识别 IBM 患者的预后因素。因此，采用线性和逻辑回归来调整潜在的混杂变量。采用多级线性回归模型来研究肌酸激酶和肌肉力量的演变。不可改变的危险因素（性别、种族、疾病持续时间和首发症状的年龄）被用作回归分析的调整协变量。
在符合 IBM 纳入标准的 335 名患者中，64%为男性，平均发病年龄为 58.7 岁，诊断延迟为 5.2 年。初始误诊（52%）和免疫抑制治疗（42%）很常见。不到一半（43%）的肌肉活检显示所有 3 种病理特征：肌内膜炎症、单核细胞浸润和边缘空泡。与非黑人患者相比，黑人患者的臂外展肌、髋屈肌和膝屈肌明显较弱。与男性患者相比，女性患者的手指屈肌和膝伸肌更强。发病年龄（<50 岁）较年轻与肌力减弱无关。
本研究表明，女性和黑人患者在广泛的 IBM 临床表型内具有不同的临床表型和病程。这些亚组对治疗的反应可能不同，这可能会影响 IBM 未来临床试验的设计。
