Utilizing biologic disease-modifying anti-rheumatic treatment sequences to subphenotype rheumatoid arthritis.
Utilizing biologic disease-modifying anti-rheumatic treatment sequences to subphenotype rheumatoid arthritis.
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DOI：
10.1186/s13075-023-03072-0
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发表时间：
2023-06-02
影响因子：
4.9
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中科院分区：
文献类型：
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许多类风湿性关节炎 (RA) 患者需要尝试多种生物疾病缓解抗风湿药 (bDMARD) 来控制其疾病。随着多种 bDMARD 选项的出现，bDMARD 的历史可能为了解 RA 亚表型提供另一种方法。本研究的目的是根据 RA 亚表型的 bDMARD 处方史确定是否存在不同的 RA 患者群。我们研究了来自经过验证的基于电子健康记录的 RA 队列的患者，数据从 2008 年 1 月 1 日到 2019 年 7 月 31 日；所有接受≥1 bDMARD 或靶向合成（ts）DMARD 治疗的受试者均被纳入。为了确定受试者是否具有相似的 b/tsDMARD 序列，将序列视为 5 类 b/tsDMARD 状态空间上的马尔可夫链。基于最大似然估计器 (MLE) 的方法用于估计马尔可夫链参数以确定聚类。研究对象的 EHR 数据进一步与包含前瞻性收集的 RA 疾病活动数据（即临床疾病活动指数 (CDAI)）的注册表相关联。作为概念证明，我们测试了源自 b/tsDMARD 序列的簇是否与临床测量相关，特别是 CDAI 的不同轨迹。我们研究了 2172 名 RA 受试者，平均年龄 52 岁，RA 持续时间 3.4 年，62% 血清反应呈阳性。我们观察了 550 个独特的 b/tsDMARD 序列，并确定了 4 个主要簇：(1) TNFi 持续者 (65.7%)、(2) TNFi 和阿巴西普治疗 (8.0%)、(3) 利妥昔单抗或多种 b/tsDMARD (12.7%)、(4) 以托珠单抗为主的多种疗法 (13.6%)。与其他组相比，TNFi 持续者随着时间的推移具有最有利的 CDAI 轨迹。我们观察到，RA 受试者可以根据一段时间内 b/tsDMARD 处方的顺序进行聚类，并且这些聚类与一段时间内疾病活动的不同轨迹相关。这项研究强调了考虑对 RA 患者进行亚表型分析的另一种方法，以进行旨在了解治疗反应的研究。
Many patients with rheumatoid arthritis (RA) require a trial of multiple biologic disease-modifying anti-rheumatic drugs (bDMARDs) to control their disease. With the availability of several bDMARD options, the history of bDMARDs may provide an alternative approach to understanding subphenotypes of RA. The objective of this study was to determine whether there exist distinct clusters of RA patients based on bDMARD prescription history to subphenotype RA. We studied patients from a validated electronic health record-based RA cohort with data from January 1, 2008, through July 31, 2019; all subjects prescribed ≥ 1 bDMARD or targeted synthetic (ts) DMARD were included. To determine whether subjects had similar b/tsDMARD sequences, the sequences were considered as a Markov chain over the state-space of 5 classes of b/tsDMARDs. The maximum likelihood estimator (MLE)-based approach was used to estimate the Markov chain parameters to determine the clusters. The EHR data of study subjects were further linked with a registry containing prospectively collected data for RA disease activity, i.e., clinical disease activity index (CDAI). As a proof of concept, we tested whether the clusters derived from b/tsDMARD sequences correlated with clinical measures, specifically differing trajectories of CDAI. We studied 2172 RA subjects, mean age 52 years, RA duration 3.4 years, and 62% seropositive. We observed 550 unique b/tsDMARD sequences and identified 4 main clusters: (1) TNFi persisters (65.7%), (2) TNFi and abatacept therapy (8.0%), (3) on rituximab or multiple b/tsDMARDs (12.7%), (4) prescribed multiple therapies with tocilizumab predominant (13.6%). Compared to the other groups, TNFi persisters had the most favorable trajectory of CDAI over time. We observed that RA subjects can be clustered based on the sequence of b/tsDMARD prescriptions over time and that the clusters were correlated with differing trajectories of disease activity over time. This study highlights an alternative approach to consider subphenotyping of patients with RA for studies aimed at understanding treatment response.
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影响因子：
3.8
作者：
Holdsworth EA;Donaghy B;Fox KM;Desai P;Collier DH;Furst DE
通讯作者：
Furst DE
影响因子：
3.8
作者：
de Haan-Rietdijk S;Kuppens P;Bergeman CS;Sheeber LB;Allen NB;Hamaker EL
通讯作者：
Hamaker EL
影响因子：
6.2
作者：
Law-Wan J;Sparfel MA;Derolez S;Azzopardi N;Goupille P;Detert J;Mulleman D;Bejan-Angoulvant T
通讯作者：
Bejan-Angoulvant T
影响因子：
4.7
作者：
Liao, Katherine P.;Cai, Tianxi;Gainer, Vivian;Goryachev, Sergey;Zeng-Treitler, Qing;Raychaudhuri, Soumya;Szolovits, Peter;Churchill, Susanne;Murphy, Shawn;Kohane, Isaac;Karlson, Elizabeth W.;Plenge, Robert M.
通讯作者：
Plenge, Robert M.
影响因子：
4.7
作者：
Fraenkel, Liana;Bathon, Joan M.;England, Bryant R.;St Clair, E. William;Arayssi, Thurayya;Carandang, Kristine;Deane, Kevin D.;Genovese, Mark;Huston, Kent Kwas;Kerr, Gail;Kremer, Joel;Nakamura, Mary C.;Russell, Linda A.;Singh, Jasvinder A.;Smith, Benjamin J.;Sparks, Jeffrey A.;Venkatachalam, Shilpa;Weinblatt, Michael E.;Al-Gibbawi, Mounir;Baker, Joshua F.;Barbour, Kamil E.;Barton, Jennifer L.;Cappelli, Laura;Chamseddine, Fatimah;George, Michael;Johnson, Sindhu R.;Kahale, Lara;Karam, Basil S.;Khamis, Assem M.;Navarro-Millan, Iris;Mirza, Reza;Schwab, Pascale;Singh, Namrata;Turgunbaev, Marat;Turner, Amy S.;Yaacoub, Sally;Akl, Elie A.
通讯作者：
Akl, Elie A.