类风湿关节炎患者的早期积极治疗会影响人类白细胞抗原II类抗原与关节损伤进展之间的关联。

Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage.

作者信息

Lard L R, Boers M, Verhoeven A, Vos K, Visser H, Hazes J M W, Zwinderman A H, Schreuder G M T, Breedveld F C, De Vries R R P, van der Linden S, Zanelli E, Huizinga T W J

机构信息

Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Arthritis Rheum. 2002 Apr;46(4):899-905. doi: 10.1002/art.10151.

DOI:10.1002/art.10151

PMID:11953965

Abstract

OBJECTIVE

The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship.

METHODS

We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method.

RESULTS

In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE- patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE- patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4- patients. Significance was confirmed by multiple regression using log-transformed scores.

CONCLUSION

Early and aggressive antirheumatic drug treatment affects the association of HLA class II alleles with progression of joint damage in RA.

摘要

目的

某些人类白细胞抗原（HLA）II类抗原的存在与类风湿关节炎（RA）关节破坏的进展密切相关。在（自身）抗原呈递后，此类抗原在诱导自身反应性T细胞形成方面可能比其他II类抗原更有效。我们研究了使用改善病情抗风湿药进行早期积极治疗是否能改变这种关系。

方法

我们分析了两项针对早期RA患者采用不同治疗策略的研究数据。第一项研究包括两个队列，一个队列（n = 109；治疗前疾病持续时间中位数为4个月）采用金字塔策略治疗（初始使用非甾体抗炎药，必要时随后使用氯喹[CQ]或柳氮磺胺吡啶[SSZ]），另一个队列（n = 97；治疗前疾病持续时间中位数为2周）立即使用CQ或SSZ治疗。第二项研究包括来自类风湿关节炎联合治疗（COBRA）试验的155例患者（疾病持续时间中位数为4个月），其中患者被随机分配接受逐步减量的泼尼松龙、甲氨蝶呤（MTX）和SSZ联合治疗（n = 76）或仅接受SSZ治疗（n = 79）。泼尼松龙和MTX剂量分别在28周和40周后逐渐减量并停用。采用改良Sharp方法测量关节损伤程度。

结果

在金字塔治疗队列中，共享表位（SE）阳性患者2年后Sharp评分的中位数增加为12，SE阴性患者为1。在立即治疗队列中，SE阳性患者的中位数增加为3，SE阴性患者为2。在COBRA研究的SSZ组中，DR4阳性患者1年后Sharp评分的中位数增加为11，DR4阴性患者为3。在联合治疗组中，DR4阳性患者的中位数增加为4，DR4阴性患者为2。使用对数转换评分的多元回归证实了显著性。