van Tuyl L H D, Lems W F, Voskuyl A E, Kerstens P J S M, Garnero P, Dijkmans B A C, Boers M
Department of Clinical Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands.
Ann Rheum Dis. 2008 Nov;67(11):1574-7. doi: 10.1136/ard.2008.090712. Epub 2008 Jul 14.
To investigate the efficacy and feasibility of an intensive combination treatment in early rheumatoid arthritis (RA) combined with monitoring both disease activity and cartilage degradation.
In a pilot trial, 21 patients with active early RA (mean DAS28 5.3; mean disease duration 3 months) were treated with COBRA treatment comprising sulfasalazine, methotrexate and high-dose step-down prednisolone, intensified by adding hydroxychloroquine and continued low-dose prednisolone. In addition, based on measurements of disease activity or a marker of cartilage degradation (CTX-II), treatment adjustments were possible with methotrexate intensification after 8 or 21 weeks; and with infliximab after 21 weeks.
Nineteen of 21 patients (90%) were in remission (DAS28 <2.6) after 40 weeks (8 weeks, 57%; 21 weeks, 76%). American College of Rheumatology (ACR) criteria, ACR20, 50, 70 and 90 improvements rates were 100%, 95%, 71% and 43% respectively. CTX-II excretion decreased by mean (SD) 347(292) ng/mmol creatinine, but only 50% of patients reduced their CTX-II excretion below the cut-off point. The two monitoring groups showed no significant difference in remission according to DAS score or CTX-II excretion, despite a trend towards more intensive treatment in the CTX-II group. Treatment intensification was feasible according to protocol.
This small pilot study suggests that intensified and tightly controlled COBRA treatment is uniquely effective in early RA.
ISRCTN96372677.
探讨强化联合治疗在早期类风湿关节炎（RA）中的疗效及可行性，并监测疾病活动度和软骨降解情况。
在一项试点试验中，21例活动期早期RA患者（平均DAS28为5.3；平均病程3个月）接受了COBRA治疗，该治疗包括柳氮磺胺吡啶、甲氨蝶呤和大剂量递减泼尼松龙，并通过加用羟氯喹强化治疗，同时持续使用低剂量泼尼松龙。此外，根据疾病活动度测量结果或软骨降解标志物（CTX-II），在8周或21周后可通过强化甲氨蝶呤进行治疗调整；21周后可使用英夫利昔单抗进行治疗调整。
21例患者中有19例（90%）在40周后达到缓解（DAS28<2.6）（8周时为57%；21周时为76%）。美国风湿病学会（ACR）标准中，ACR20、50、70和90改善率分别为100%、95%、71%和43%。CTX-II排泄量平均（标准差）下降了347（292）ng/mmol肌酐，但只有50%的患者将CTX-II排泄量降至临界值以下。尽管CTX-II组有更强化治疗的趋势，但两个监测组在根据DAS评分或CTX-II排泄量判断的缓解情况方面无显著差异。根据方案，治疗强化是可行的。
这项小型试点研究表明，强化且严格控制的COBRA治疗在早期RA中具有独特的疗效。
ISRCTN96372677。
