Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide.
Elevated liver enzyme tests among patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate and/or leflunomide.
复制标题
DOI：
10.1136/ard.2008.101378
复制
发表时间：
2010-01
影响因子：
27.4
通讯作者：
Kremer JM
中科院分区：
文献类型：
--
作者：
Curtis JR;Beukelman T;Onofrei A;Cassell S;Greenberg JD;Kavanaugh A;Reed G;Strand V;Kremer JM
与疾病修饰抗风湿药[DMARDs]相关的潜在肝毒性需要实验室监测。在类风湿和银屑病关节炎[RA， PsA]患者中，我们检测了甲氨蝶呤（MTX）、来氟米特（LEF）和MTX+LEF与其他DMARDs相关的丙氨酸/天冬氨酸转氨酶（ALT/AST）酶升高的发生率。纳入北美风湿病研究人员联盟（CORRONA）启动dmard的RA和PsA患者被确定。当超过正常上限（ULN）的1或2倍时，即可确定异常。使用广义估计方程估计MTX/LEF剂量与ALT/AST酶升高之间的比值比[OR]。使用MTX+LEF的相互作用项量化了与每个单独相比组合的增量风险。在接受MTX、LEF、MTX+LEF或两者均不接受的RA患者中，分别有22%、17%、31%和14%的患者出现ALT/AST水平升高（bbb1x ULN）；PsA患者升高的可能性是前者的2.76倍（95% CI 1.84 - 4.15）。MTX或LEF单药治疗的患者中，1-2%的患者出现了bb20 × ULN升高，而联合治疗的患者中，这一比例为5%。多变量调整后，与单药治疗相比，MTX + LEF联合用药的风险更高，根据作为联合用药的MTX剂量：MTX 10-17.5mg /周，OR=2.91（95%可信区间[CI] 1.23-6.90）和MTX≥20 mg/周，OR=3.98 （95% CI: 1.72-9.24）。在接受DMARD治疗的RA和PsA患者中，14-35%出现ALT/AST水平异常。PsA患者和接受MTX（≥10mg/天）+ LEF治疗的患者的风险逐渐增加。这些发现应该有助于监测这些患者群体中潜在的肝毒性。
Potential hepatotoxicity associated with disease modifying anti-rheumatic drugs [DMARDs] requires laboratory monitoring. In rheumatoid and psoriatic arthritis [RA, PsA] patients, we examined the incidence of elevated alanine/aspartate aminotransferase (ALT/AST) enzymes associated with methotrexate (MTX), leflunomide (LEF), and MTX+LEF vs. other DMARDs. RA and PsA patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) initiating DMARDs were identified. Abnormalities were identified when either was 1 or 2-fold time above the upper limits of normal (ULN). Odds ratios [OR] between MTX/LEF dose and elevated ALT/AST enzymes were estimated using generalized estimating equations. Interaction terms for use of MTX+LEF quantified the incremental risk of the combination compared to each individually. Elevated ALT/AST levels (>1× ULN) occurred in 22, 17, 31, and 14% RA patients receiving MTX, LEF, MTX+LEF, or neither, respectively; elevations were 2.76 fold (95% CI 1.84 – 4.15) more likely in PsA patients. Elevations > 2× ULN occurred in 1–2% of patients on MTX or LEF monotherapy compared to 5% with the combination. After multivariable adjustment and compared with either monotherapy, combination MTX + LEF was associated with greater risk according to MTX dose used as part of the combination: MTX 10–17.5mg/week, OR=2.91 (95% confidence interval [CI] 1.23–6.90) and MTX ≥20 mg/week, OR=3.98 (95% CI: 1.72–9.24). 14–35% of RA and PsA patients initiating DMARD therapy developed abnormal ALT/AST levels. Risks were incrementally greater in those with PsA and in those receiving MTX (≥ 10mg/day) + LEF. These findings should help inform monitoring for potential hepatotoxicity in these patient populations.
登录
查看更多内容
影响因子：
--
作者：
KREMER, JM;GALIVAN, J;KAMEN, B
通讯作者：
KAMEN, B
影响因子：
39.2
作者：
Kremer, JM;Genovese, MC;Bathon, JM
通讯作者：
Bathon, JM
影响因子：
--
作者：
KREMER, JM;LEE, RG;TOLMAN, KG
通讯作者：
TOLMAN, KG
影响因子：
5.5
作者：
Emery, P;Breedveld, FC;Loew-Friedrich, I
通讯作者：
Loew-Friedrich, I
影响因子：
--
作者：
KREMER, JM;KAYE, GI;AXIOTIS, CA
通讯作者：
AXIOTIS, CA