Abstract：
Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12 weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA.
摘要：
托法替尼是第一个被批准用于治疗类风湿性关节炎（RA）的口服JAK抑制剂。为了增强我们对托法替尼药物反应的理解，我们使用层次聚类在真实世界环境中分析对治疗有反应的患者的概况.从马来西亚的12个主要风湿病中心选择开始接受托法替尼治疗的患者。目的是评估他们对托法替尼的反应，定义为在12周时达到DAS28-CRP/ESR≤3.2和DAS28改善>1.2。使用基线时的社会人口统计学和临床参数进行分层聚类分析。根据基线时的特定临床因素，包括骨侵蚀，将163例RA患者分为3组（组1、2和3）。抗体阳性，疾病活动和贫血状态。第1组包括没有骨侵蚀的RA患者，抗体阴性,低基线疾病活动测量和无贫血。第2组包括没有骨侵蚀的患者，射频阳性,反CCP的消极情绪，中度至高度基线疾病活动评分和无贫血.第3组患者骨侵蚀，抗体阳性，高基线疾病活动和贫血。托法替尼的反应率在集群之间有所不同：集群1的反应率为79%，二组的反应率为66%,第3组的反应率为36%。发现三个集群之间的响应率差异具有统计学意义。这项聚类分析研究表明，血清阴性且疾病活动性低的患者，没有骨侵蚀和没有贫血迹象可能有更高的可能性受益于托法替尼治疗。通过确定对托法替尼治疗有反应的临床特征，我们可以改善治疗分层,为RA患者带来显著的获益和更好的健康结局.
