Hurst Stacey, Kallan Michael J, Wolfe Frederick J, Fries James F, Albert Daniel A
Division of Rheumatology, University of Pennsylvania, Philadelphia 19104-4283, USA.
J Rheumatol. 2002 Aug;29(8):1639-45.
The use of disease modifying antirheumatic drugs (DMARD) for rheumatoid arthritis (RA) is predicated on the expected value of the treatment course. Most clinical data are generalized from randomized controlled trials (RCT), which may result in estimates that are discordant with clinical experience and cannot address the effects of sequence of drugs. We computed estimates of relative DMARD effectiveness from a large observational database using area under the curve (AUC) data.
We examined data collected over a 20 year period on 1160 patients who were followed at the Wichita Arthritis Center. We utilized Health Assessment Questionnaire (HAQ) disability index data to quantify the effect of methotrexate (MTX), hydroxychloroquine (HCQ), and injectable gold (gold) on subsequent patient outcome. Using an AUC analysis, we compared length of treatment course, total disability averted, annual disability averted, and percentage of possible disability averted across drugs, and examined differences between first courses of therapy in DMARD naive patients and subsequent courses of the same and different DMARD in patients.
Patients treated with MTX, HCQ, and gold improved at a rate of -0.33, -0.18 and -0.38 annualized HAQ area units, respectively. Since duration taking drug was greatest for MTX, then HCQ, then gold, the cumulative improvement was greatest with MTX (-1.07) versus gold (-0.74) versus HCQ (-0.47) in disability unit years. All 3 drugs were better cumulatively with earlier disease (MTX-1.74 for < 1 yr vs -0.95 for > 1 yr; HCQ -0.68 vs -0.43; gold -1.71 vs -0.49). A second trial of the same drug was far less effective than the first course. On a percentage of possible improvement basis, these drugs were nearly equal since HCQ is given to less severely affected patients.
MTX is the most effective DMARD of these 3 because of the length the therapeutic segment. In terms of disability averted, none of the agents decrease disability by more than 25% of the theoretically possible improvement. We documented that effectiveness of RA treatment is a function of drug sequence, duration of disease, whether it is a first or second course, and severity of disease. None of these clinically relevant observations have emerged from clinical trials. These methodologic approaches provide important quantitative comparative data and will be useful in further assessment of the relative effectiveness of present and future DMARD.
使用改善病情抗风湿药物（DMARD）治疗类风湿关节炎（RA）是基于治疗过程的预期价值。大多数临床数据来自随机对照试验（RCT）的归纳总结，这可能导致估计值与临床经验不一致，且无法解决药物使用顺序的影响。我们使用曲线下面积（AUC）数据，从一个大型观察性数据库中计算DMARD相对有效性的估计值。
我们检查了威奇托关节炎中心在20年期间收集的1160例患者的数据。我们利用健康评估问卷（HAQ）残疾指数数据来量化甲氨蝶呤（MTX）、羟氯喹（HCQ）和注射用金制剂（金）对后续患者结局的影响。通过AUC分析，我们比较了不同药物的治疗疗程长度、避免的总残疾、每年避免的残疾以及避免的可能残疾百分比，并研究了初治DMARD患者的首个疗程与同一患者后续使用相同或不同DMARD疗程之间的差异。
接受MTX、HCQ和金制剂治疗的患者，每年HAQ面积单位改善率分别为-0.33、-0.18和-0.38。由于服用MTX的时间最长，其次是HCQ，然后是金制剂，在残疾单位年方面，MTX的累积改善最大（-1.07），其次是金制剂（-0.74），然后是HCQ（-0.47）。所有3种药物在疾病早期累积效果更好（MTX：病程<1年时为-1.74，病程>1年时为-0.95；HCQ：-0.68对-0.43；金制剂：-1.71对-0.49）。同一种药物的第二个疗程效果远不如首个疗程。基于可能改善的百分比，这些药物几乎相当，因为HCQ用于病情较轻的患者。
由于治疗疗程长度，MTX是这3种药物中最有效的DMARD。就避免的残疾而言，没有一种药物能将残疾减少超过理论上可能改善的25%。我们证明RA治疗的有效性是药物顺序、病程、是首个疗程还是第二个疗程以及疾病严重程度的函数。这些临床相关观察结果均未从临床试验中得出。这些方法提供了重要的定量比较数据，将有助于进一步评估当前和未来DMARD的相对有效性。
