Treatment of early seropositive rheumatoid arthritis - Doxycycline plus methotrexate versus methotrexate alone
Treatment of early seropositive rheumatoid arthritis - Doxycycline plus methotrexate versus methotrexate alone
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DOI：
10.1002/art.21620
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发表时间：
2006-02-01
影响因子：
--
通讯作者：
Leff, RD
中科院分区：
文献类型：
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作者：
O'Dell, JR;Elliott, JR;Leff, RD
客观的。比较强力霉素联合甲氨蝶呤 (MTX) 与单独使用 MTX 治疗早期血清阳性类风湿性关节炎 (RA) 的疗效，并尝试区分强力霉素的抗菌和抗金属蛋白酶作用。方法。 66 名病程 < 1 年的血清阳性 RA 患者，既往未接受过缓解病情抗风湿药物治疗，被随机接受 100 mg 强力霉素每日两次联合 MTX（高剂量强力霉素组）、20 mg 强力霉素每日两次联合 MTX（低剂量强力霉素组）或安慰剂联合 MTX（安慰剂组），为期 2 年双盲研究。治疗开始时使用 7.5 毫克/周的 MTX 剂量，每 3 个月滴定一次，直至达到缓解（最大剂量为 17.5 毫克/周）。主要终点是美国风湿病学会 2 年后反应改善 50% (ACR50)。结果。在高剂量多西环素组中观察到 ACR50 反应的患者比例为 41.6%，在低剂量多西环素组中为 38.9%，在安慰剂组中为 12.5%。高剂量多西环素组与安慰剂组的 ACR50 反应卡方分析结果显着不同（P = 0.02）。趋势分析显示，组间 ACR20 反应和 ACR50 反应存在显着差异（分别为 P = 0.04 和 P = 0.03）。 2 年时的 MTX 剂量在各组之间没有差异。高剂量多西环素组4名患者、低剂量多西环素组2名患者、安慰剂组2名患者因毒性反应退出。结论。在早期血清阳性 RA 患者中，MTX 加强力霉素的初始治疗优于单独使用 MTX 的治疗（基于 ACR50 反应）。对低剂量和高剂量多西环素的治疗反应相似，表明抗金属蛋白酶作用比抗菌作用更重要。需要进一步研究评估四环素类药物在 RA 中的作用机制。
Objective. To compare the efficacy of doxycycline plus methotrexate (MTX) versus MTX alone in the treatment of early seropositive rheumatoid arthritis (RA), and to attempt to differentiate the antibacterial and antimetalloproteinase effects of doxycycline.Methods. Sixty-six patients with seropositive RA of < 1 year's duration who had not been previously treated with disease-modifying antirheumatic drugs were randomized to receive 100 mg of doxycycline twice daily with MTX (high-dose doxycycline group), 20 mg of doxycycline twice daily with MTX (low-dose doxycycline group), or placebo with MTX (placebo group), in a 2-year double-blind study. Treatment was started with an MTX dosage of 7.5 mg/week, which was titrated every 3 months until remission was reached (maximum dosage of 17.5 mg/week). The primary end point was an American College of Rheumatology 50% improvement (ACR50) response at 2 years.Results. ACR50 responses were observed in 41.6% of patients in the high-dose doxycycline group, 38.9% of those in the low-dose doxycycline group, and 12.5% of patients in the placebo group. Results of chi-square analysis of the ACR50 response in the high-dose doxycycline group versus that in the placebo group were significantly different (P = 0.02). Trend analysis revealed that the ACR20 response and the ACR50 response were significantly different between groups (P = 0.04 and P = 0.03, respectively). MTX doses at 2 years were not different among groups. Four patients in the high-dose doxycycline group, 2 patients in the low-dose doxycycline group, and 2 patients in the placebo group were withdrawn because of toxic reactions.Conclusion. In patients with early seropositive RA, initial therapy with MTX plus doxycycline was superior (based on an ACR50 response) to treatment with MTX alone. The therapeutic responses to low-dose and high-dose doxycycline were similar, suggesting that the antimetalloproteinase effects were more important than the antibacterial effects. Further studies to evaluate the mechanism of action of tetracyclines in RA are indicated.