Ng Bernard, Chu Adeline
Michael E. DeBakey VA Medical Center Health Services Research and Development Center of Excellence, 2002 Holcombe Blvd Mail Stop 111K, Houston, TX, USA,
Clin Rheumatol. 2014 Jan;33(1):21-30. doi: 10.1007/s10067-013-2353-9. Epub 2013 Aug 11.
The purpose of this study is to explore patient factors associated with differences in methotrexate (MTX) dosing and to compare patient factors and MTX-dosing patterns between those who remained on MTX monotherapy and those who were switched or had additional therapy. A retrospective cohort of 7,017 patients with newly diagnosed rheumatoid arthritis (RA) was identified in the United States Department of Veterans Affairs administrative databases between 1 October 1999 and 30 September 2009. Regression analyses were used to study the association of MTX start and maximum dose attained with various patient characteristics and compare differences between groups who had therapeutic change (having switched to or added another anti-rheumatic agent or having steroids increased by 2.5 mg of prednisone or equivalent) with those remaining on MTX monotherapy. Abnormal serum creatinine (>1.5 mg/dL) was associated lower start and peak MTX doses (p < 0.01). Older RA patients were less likely to attain peak MTX dose of 15 mg or more (p < 0.01). Males and patients 75 and older (compared with <45) had lower risk of therapeutic change (hazard ratio, [HR] 0.80, 95 % confidence interval [CI] 0.72-0.90, and HR 0.42, 95% CI 0.42-0.36-0.50, respectively). Patients who attained higher peak MTX dose had lower risk of therapeutic change compared with those dosed at less than 15 mg/week (HR 0.85, 95% CI 0.77-0.92 for 15 to <20 and HR 0.79, 95% CI 0.72-0.86 for 20 or more). Injectable MTX use conferred lower risk of therapeutic change (HR 0.64, 95% CI 0.52-0.78). Two thirds did not attain a maximum MTX dose of 20 mg/week or more before therapeutic change occurred. Older age and renal insufficiency were barriers to the use of higher MTX maximum dosages. Use of injectable MTX and higher maximum MTX dose were independently associated with higher likelihood to remain on MTX monotherapy. Further studies are needed to explore targeted interventions that may optimize MTX dosing to improve success rates of MTX monotherapy.
本研究的目的是探索与甲氨蝶呤（MTX）剂量差异相关的患者因素，并比较持续接受MTX单药治疗的患者与改用其他治疗或接受附加治疗的患者之间的患者因素及MTX给药模式。1999年10月1日至2009年9月30日期间，在美国退伍军人事务部行政数据库中确定了一个包含7017例新诊断类风湿关节炎（RA）患者的回顾性队列。采用回归分析研究MTX起始剂量和达到的最大剂量与各种患者特征之间的关联，并比较治疗发生改变（改用或加用另一种抗风湿药物，或泼尼松或等效药物增加2.5mg）的组与持续接受MTX单药治疗的组之间的差异。血清肌酐异常（>1.5mg/dL）与MTX起始剂量和峰值剂量较低相关（p<0.01）。老年RA患者达到15mg或更高MTX峰值剂量的可能性较小（p<0.01）。男性以及75岁及以上的患者（与年龄小于45岁的患者相比）治疗改变的风险较低（风险比[HR]分别为0.80，95%置信区间[CI]为0.72 - 0.90；HR为0.42，95%CI为0.36 - 0.50）。与每周剂量低于15mg的患者相比，达到较高MTX峰值剂量的患者治疗改变的风险较低（15至<20mg时HR为0.85，95%CI为0.77 - 0.92；20mg或更高时HR为0.79，95%CI为0.72 - 0.86）。使用注射用MTX可降低治疗改变的风险（HR为0.64，95%CI为0.52 - 0.78）。在治疗改变发生之前，三分之二的患者未达到每周20mg或更高的MTX最大剂量。老年和肾功能不全是使用更高MTX最大剂量的障碍。使用注射用MTX和更高的MTX最大剂量与更有可能持续接受MTX单药治疗独立相关。需要进一步研究探索有针对性的干预措施，以优化MTX剂量，提高MTX单药治疗的成功率。
