Morgan C, Lunt M, Brightwell H, Bradburn P, Fallow W, Lay M, Silman A, Bruce I N
Arthritis Research Campaign (ARC) Epidemiology Unit, University of Manchester Medical School, Oxford Road, Manchester, M13 9PT, UK.
Ann Rheum Dis. 2003 Jan;62(1):15-9. doi: 10.1136/ard.62.1.15.
There is a wide variation in responses to standard disease modifying antirheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). Whether multidrug resistance, failure to respond to several DMARDs, is a specific entity over and above that expected by chance alone is unclear.
To identify patients with RA who demonstrate a multidrug resistant phenotype and to determine what proportion of the variance in drug responses is due to patient related factors.
Patients with RA (1987 American College of Rheumatology criteria) were identified from clinics at Manchester Royal Infirmary and through the Arthritis Research Campaign National RA Repository. The clinic records were reviewed and multidrug resistance was defined as stopping three or more DMARDs owing to lack of efficacy after an adequate trial of the drug. Logistic regression measured by a random effects model was used to determine the relative contribution of the drug and subject related differences to the multidrug resistance.
265 patients (210 (79.3%) female) were studied. The mean (SD) age and disease duration were 52.2 (12.9) and 10.7 (8.8) years, respectively. Patients had a median (range) of 2 (1-8) DMARD courses. Failure of at least one DMARD due to inefficacy occurred in 105 (40%) and 13 (5%) were multidrug resistant. Overall, 35% of the variance in drug responses was due to between-subject differences (p=0.02). Rheumatoid factor (RF) status contributed significantly to this (OR=2.15, 95% confidence interval (95% CI) 1.00 to 4.62) but explained only 3% of the total variance in drug inefficacy.
Multidrug resistance occurs in an uncommon (5%) but important subgroup of patients with RA. The between-subject variance is not fully explained by demographics and RF status. Understanding the biological mechanisms that contribute to multidrug resistance may suggest new therapeutic approaches and targets in RA.
类风湿关节炎（RA）患者对标准抗风湿病情改善药（DMARD）治疗的反应差异很大。多药耐药（即对多种DMARD均无反应）是否是一种超出偶然预期的特定实体尚不清楚。
识别表现出多药耐药表型的RA患者，并确定药物反应差异中因患者相关因素所致的比例。
从曼彻斯特皇家医院的诊所及关节炎研究运动全国RA数据库中识别出符合1987年美国风湿病学会标准的RA患者。查阅临床记录，多药耐药定义为在对药物进行充分试验后，因疗效不佳而停用三种或更多DMARD。采用随机效应模型测量的逻辑回归来确定药物和受试者相关差异对多药耐药的相对贡献。
共研究了265例患者（210例（79.3%）为女性）。平均（标准差）年龄和病程分别为52.2（12.9）岁和10.7（8.8）年。患者接受DMARD疗程的中位数（范围）为2（1 - 8）个。105例（40%）患者至少有一种DMARD因无效而停用，13例（5%）为多药耐药。总体而言，药物反应差异的35%归因于受试者间差异（p = 0.02）。类风湿因子（RF）状态对此有显著贡献（比值比 = 2.15，95%置信区间（95%CI）为1.00至4.62），但仅解释了药物无效总差异的3%。
多药耐药发生在RA患者中一个不常见（5%）但重要的亚组中。受试者间差异不能完全由人口统计学特征和RF状态来解释。了解导致多药耐药的生物学机制可能为RA提示新的治疗方法和靶点。
