van der Kooij Sjoerd M, de Vries-Bouwstra Jeska K, Goekoop-Ruiterman Yvonne P M, van Zeben Derkjen, Kerstens Pit J S M, Gerards Andreas H, van Groenendael Johannes H L M, Hazes Johanna M W, Breedveld Ferdinand C, Allaart Cornelia F, Dijkmans Ben A C
Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, Netherlands.
Ann Rheum Dis. 2007 Oct;66(10):1356-62. doi: 10.1136/ard.2006.066662. Epub 2007 Feb 9.
To determine the efficacy of subsequent disease modifying antirheumatic drug (DMARD) therapies after initial methotrexate (MTX) failure in patients with recent onset rheumatoid arthritis (RA), treated according to the DAS for 2 years.
In groups 1 and 2 of the BeSt study, 244 RA patients were initially treated with MTX 15-25 mg/week. Patients who discontinued MTX because of insufficient clinical response (disease activity score, DAS >2.4) or toxicity were classified as "MTX failures." In group 1, these patients switched to sulfasalazine (SSA), then leflunomide and finally to MTX + infliximab (IFX). In group 2, "MTX failures" added SSA to MTX, then hydroxychloroquine (HCQ), then prednisone, and eventually switched to MTX + IFX. "MTX successes" were patients who achieved a DAS </=2.4 after 2 years while still on MTX monotherapy. Total Sharp/van der Heijde score (TSS) progression from 0-2 years was assessed in "MTX failures" versus "MTX successes."
After 2 years, 162/244 patients (66%) had discontinued MTX because of insufficient response or toxicity. Of these, 78% also failed on SSA (adding or switching), 87% subsequently failed on leflunomide (in group 1), and 64% on MTX + SSA + HCQ (in group 2). 34 of 48 patients (71%) in groups 1 and 2 were successfully treated with MTX + IFX. After 2 years, regardless of the "success" on subsequent DMARDs, " MTX failures" had a median TSS progression of 3 units (mean 9) versus 1 unit (mean 3) in "MTX successes" (p = 0.007).
After failure on initial MTX, treatment with subsequent conventional DMARDs is unlikely to result in a DAS </=2.4 and allows progression of joint damage.
确定在根据疾病活动度评分（DAS）治疗2年的近期发病类风湿关节炎（RA）患者中，初始甲氨蝶呤（MTX）治疗失败后后续使用改善病情抗风湿药（DMARD）治疗的疗效。
在BeSt研究的第1组和第2组中，244例RA患者最初接受每周15 - 25 mg MTX治疗。因临床反应不足（疾病活动评分，DAS>2.4）或毒性而停用MTX的患者被归类为“MTX治疗失败”。在第1组中，这些患者转而使用柳氮磺胺吡啶（SSA），然后是来氟米特，最后是MTX +英夫利昔单抗（IFX）。在第2组中，“MTX治疗失败”的患者在MTX基础上加用SSA，然后是羟氯喹（HCQ），然后是泼尼松，最终转而使用MTX + IFX。“MTX治疗成功”的患者是在2年时仍接受MTX单药治疗且DAS≤2.4的患者。评估“MTX治疗失败”患者与“MTX治疗成功”患者从0至2年的总Sharp/van der Heijde评分（TSS）进展情况。
2年后，162/244例患者（66%）因反应不足或毒性而停用MTX。其中，78%的患者在使用SSA（加用或换药）时也治疗失败，87%的患者随后在使用来氟米特时失败（第1组），64%的患者在使用MTX + SSA + HCQ时失败（第2组）。第1组和第2组的48例患者中有34例（71%）使用MTX + IFX治疗成功。2年后，无论后续DMARD治疗是否“成功”，“MTX治疗失败”患者的TSS进展中位数为3个单位（平均9个单位），而“MTX治疗成功”患者为1个单位（平均3个单位）（p = 0.007）。
初始MTX治疗失败后，后续使用传统DMARD治疗不太可能使DAS≤2.4，并会导致关节损伤进展。
