Department of Rheumatology, 424 General Military Hospital, Thessaloniki, Greece.
Clin Rheumatol. 2012 Jan;31(1):163-7. doi: 10.1007/s10067-011-1842-y. Epub 2011 Sep 9.
The recommendations of the European League Against Rheumatism (EULAR) for the management of rheumatoid arthritis (RA) suggest a different therapeutic approach to methotrexate (MTX) resistance according to the presence or absence of poor prognostic factors. Retrospectively, in our patients with active early RA (disease activity score in 28 joints (DAS28) > 3.2) that failed to respond to initial MTX monotherapy, we investigated whether leflunomide (LEF) addition had a different efficacy when associated with the presence or absence of poor prognostic factors. Of the 20 patients who received LEF, 15 (2 males and 13 females) tolerated the combination. Five patients had no poor prognostic factors, and 4 (80%) of those patients achieved remission or low disease activity (LDA) according to DAS28 and also a good response with the EULAR criteria. Of the 10 patients with at least one poor prognostic factor, remission or LDA occurred in 4 (40%) of the patients, and a good EULAR response was obtained in 3 (30%) of the patients. By Fisher's exact test, no significant difference was found between the two groups of patients in remission or LDA (p = 0.28) according to DAS28 and a good response (p = 0.12) with the EULAR criteria. In all patients with an inadequate response to the LEF+MTX combination, the substitution of a TNF inhibitor for LEF or the addition of a TNF inhibitor to the combination led to remission or LDA. Large studies are required to investigate the efficacy of LEF addition in relation to prognostic factors in patients with active early RA that did not respond to the initial therapy with MTX alone.
欧洲抗风湿病联盟（EULAR）关于类风湿关节炎（RA）管理的建议根据是否存在预后不良因素，提出了一种不同于甲氨蝶呤（MTX）耐药的治疗方法。回顾性地，在我们患有活动期早期 RA（28 个关节疾病活动评分（DAS28）>3.2）且对初始 MTX 单药治疗无反应的患者中，我们研究了当联合使用来氟米特（LEF）时，其在存在或不存在预后不良因素时的疗效是否不同。在接受 LEF 治疗的 20 名患者中，有 15 名（2 名男性和 13 名女性）能够耐受联合治疗。5 名患者无预后不良因素，其中 4 名（80%）患者根据 DAS28 达到缓解或低疾病活动度（LDA），也根据 EULAR 标准获得良好反应。在 10 名至少存在一个预后不良因素的患者中，4 名（40%）患者达到缓解或 LDA，3 名（30%）患者获得 EULAR 良好反应。Fisher 确切概率检验显示，两组患者在根据 DAS28 达到缓解或 LDA（p=0.28）和根据 EULAR 标准获得良好反应（p=0.12）方面无显著差异。在所有对 LEF+MTX 联合治疗反应不足的患者中，用 TNF 抑制剂替代 LEF 或在联合治疗中添加 TNF 抑制剂，可使患者达到缓解或 LDA。需要进行大型研究，以研究 LEF 联合治疗在对单独使用 MTX 初始治疗无反应的活动期早期 RA 患者中的疗效与预后因素的关系。
