COBRA combination therapy in patients with early rheumatoid arthritis -: Long-term structural benefits of a brief intervention
COBRA combination therapy in patients with early rheumatoid arthritis -: Long-term structural benefits of a brief intervention
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DOI：
10.1002/art.10083
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发表时间：
2002-02-01
影响因子：
--
通讯作者：
van der Linden, S
中科院分区：
文献类型：
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作者：
Landewé, RBM;Boers, M;van der Linden, S
目标。联合治疗类风湿性关节炎（COBRA）试验表明，强的松龙、甲氨蝶呤和柳氮磺胺嘧啶（SSZ）的降压联合治疗在抑制类风湿性关节炎（RA）的疾病活动性和放射学进展方面优于SSZ单药治疗。目前的研究是为了调查COBRA治疗的益处是否能持续一段时间，并确定哪些基线因素可以预测结果。所有患者都参加了为期56周的COBRA试验。在随访期间，他们由自己的风湿病学家进行检查，并由研究护士定期进行评估；没有指定治疗方案。疾病活动性、放射损伤和功能能力是主要结果域。两名独立评审员按照Sharp/van der Heijde方法依次对x光片评分。从COBRA试验最后一次访问时（基线后56周）获得的数据开始，根据治疗意向通过广义估计方程对结果进行分析。在随访开始时，与SSZ单药治疗组相比，COBRA组患者的平均时间平均28关节疾病活动评分（DAS28）和中位放射学损伤评分（Sharp）显著降低。两组患者功能能力评分（健康评估问卷[HAQ]）差异无统计学意义。在4-5年的随访期间，SSZ组的时间平均DAS28每年下降0.17分，COBRA组每年下降0.07分。SSZ组的夏普进展率为每年8.6点，COBRA组为5.6点。在调整了治疗和随访期间疾病活动度的差异后，放射学进展率的组间差异为每年3.7个点。HAQ分数随时间变化不显著。随时间放射学进展的独立基线预测因子（除治疗分配外）是类风湿因子阳性、夏普评分和das28。最初6个月周期的强化联合治疗，包括高剂量皮质类固醇，可持续抑制早期RA患者的放射学进展率，独立于随后的抗风湿病治疗。
Objective. The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome.Methods. All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline).Results. At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28 joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ mono-therapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28.Conclusion. An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.