Rheumatology Research Unit, Instituto de Medicina Molecular - Faculdade de Medicina da Universidade de Lisboa, Edifício Egas Moniz - Av, Prof, Egas Moniz, Lisboa 1649-028, Portugal.
BMC Med. 2013 Jan 23;11:17. doi: 10.1186/1741-7015-11-17.
Methotrexate (MTX) is the central drug in the management of rheumatoid arthritis (RA) and other immune mediated inflammatory diseases. It is widely used either in monotherapy or in association with other synthetic and biologic disease modifying anti-rheumatic drugs (DMARDs). Although comprehensive clinical experience exists for MTX and synthetic DMARDs, to date it has not been possible to preview correctly whether or not a patient will respond to treatment with these drugs. Predicting response to MTX and other DMARDs would allow the selection of patients based on their likelihood of response, thus enabling individualized therapy and avoiding unnecessary adverse effects and elevated costs. However, studies analyzing this issue have struggled to obtain consistent, replicable results and no factor has yet been recognized to individually distinguish responders from nonresponders at treatment start. Variables possibly influencing drug effectiveness may be disease-, patient- or treatment-related, clinical or biological (genetic and nongenetic). In this review we summarize current evidence on predictors of response to MTX and other synthetic DMARDs, discuss possible causes for the heterogeneity observed and address its translation into daily clinical practice.
甲氨蝶呤（MTX）是治疗类风湿关节炎（RA）和其他免疫介导的炎症性疾病的核心药物。它广泛用于单药治疗或与其他合成和生物 DMARD 联合治疗。尽管 MTX 和合成 DMARD 有全面的临床经验，但迄今为止，还不可能正确预测患者是否会对这些药物的治疗有反应。预测对 MTX 和其他 DMARD 的反应将允许根据患者的反应可能性进行选择，从而实现个体化治疗，并避免不必要的不良反应和增加成本。然而，分析这一问题的研究一直难以获得一致、可复制的结果，而且还没有任何因素能够单独区分治疗开始时的应答者和无应答者。可能影响药物有效性的变量可能与疾病、患者或治疗有关，包括临床或生物学因素（遗传和非遗传因素）。在这篇综述中，我们总结了目前关于 MTX 和其他合成 DMARD 反应预测因子的证据，讨论了观察到的异质性的可能原因，并探讨了其在日常临床实践中的转化。
