First Department of Propedeutic and Internal Medicine, Laikon Hospital, Athens, Greece.
Semin Arthritis Rheum. 2013 Feb;42(4):377-90. doi: 10.1016/j.semarthrit.2012.06.001. Epub 2012 Jul 11.
Experimental and clinical evidence suggest a therapeutic role for the tyrosine kinase inhibitor imatinib in fibrosing conditions. We evaluated published data on the safety and efficacy of imatinib for patients with systemic sclerosis (SSc), a severe autoimmune disease with significant morbidity and mortality.
A careful search for all original articles and abstracts on the use of imatinib in SSc published in English from 2008 through February 2012 was performed. Two additional patients from our center are also described.
Five small observational clinical trials on the use of imatinib in severe SSc have been conducted and case reports and small series of refractory to current approaches patients have been reported, adding to a total of 108 patients having received this drug to date. In most of these patients imatinib was given for skin or pulmonary fibrosis. Encouraging results were reported in 3 of 4 studies, whereas the fifth study was prematurely terminated for safety reasons. Overall, clinical results are highly variable, ranging from ineffective or toxic responses to extremely encouraging clinical improvements in some severely ill patients. These discrepancies could partly reflect imatinib-related safety issues, in particular, SSc patients or idiosyncratic resistance to imatinib, as happens in chronic myelogenous leukemia and gastrointestinal stromal tumors, the drug's approved indications.
The limited available experience suggests that imatinib could be considered as an individualized treatment approach in severe SSc and underscores the need to identify markers for selecting particular patients, who will safely respond to therapeutic inhibition of tyrosine kinases.
实验和临床证据表明，酪氨酸激酶抑制剂伊马替尼在纤维性疾病中具有治疗作用。我们评估了已发表的关于伊马替尼治疗系统性硬化症（SSc）患者的安全性和疗效的数据，SSc 是一种严重的自身免疫性疾病，具有较高的发病率和死亡率。
我们仔细搜索了 2008 年至 2012 年 2 月期间以英文发表的关于伊马替尼在 SSc 中应用的所有原始文章和摘要。另外还描述了我们中心的另外 2 名患者。
已经进行了五项关于伊马替尼在严重 SSc 中应用的小型观察性临床试验，并且已经报道了针对现有方法难治的病例报告和小系列患者，迄今为止共有 108 名患者接受了这种药物。在大多数这些患者中，伊马替尼用于治疗皮肤或肺纤维化。四项研究中的三项报告了令人鼓舞的结果，而第五项研究因安全性原因而提前终止。总体而言，临床结果高度可变，范围从无效或毒性反应到一些重病患者的极有希望的临床改善。这些差异可能部分反映了与伊马替尼相关的安全性问题，特别是 SSc 患者或对伊马替尼的特发性耐药性，就像在慢性髓性白血病和胃肠道间质瘤中一样，这是该药的批准适应症。
有限的可用经验表明，伊马替尼可被视为严重 SSc 的个体化治疗方法，并强调需要确定标记物以选择将安全响应治疗性抑制酪氨酸激酶的特定患者。
