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在临床实践中,类风湿性关节炎患者从英夫利昔单抗换用第二种肿瘤坏死因子α抑制剂是否有益?

Do rheumatoid arthritis patients in clinical practice benefit from switching from infliximab to a second tumor necrosis factor alpha inhibitor?

作者信息

Hjardem Elisabeth, Østergaard Mikkel, Pødenphant Jan, Tarp Ulrik, Andersen Lis Smedegaard, Bing Jette, Peen Elisabeth, Lindegaard Hanne Merete, Ringsdal Vibeke Stevenius, Rødgaard Anne, Skøt Jens, Hansen Annette, Mogensen Hans Henrik, Unkerskov Janne, Hetland Merete Lund

机构信息

Department of Rheumatology, Copenhagen University Hospital, Hvidovre, Denmark.

出版信息

Ann Rheum Dis. 2007 Sep;66(9):1184-9. doi: 10.1136/ard.2006.054742. Epub 2007 Mar 27.

Abstract

OBJECTIVE

To investigate the efficacy of switching to a second biological drug in rheumatoid arthritis (RA) patients.

METHODS

Since 2000, Danish RA patients (n = 1021) receiving biological therapy have been registered in the nationwide DANBIO database. The first and second treatment series of patients, who switched therapy before 2005 (n = 235), were analysed for their reasons for switching, Disease Activity Score 28 (DAS28), DAS28 improvement, European League against Rheumatology (EULAR) response and drug survival. Most patients switched from infliximab to etanercept or adalimumab.

RESULTS

Median survivals for switchers' first/second treatment were 37/92 weeks (all patients' first treatment 119 weeks). Reasons for switching were lack of efficacy (LOE; 109 patients), adverse events (AE; 72), other reasons (54). If patients experienced AE to the first drug, 15% had AE to the second. Median DAS28 improvements in first/second treatment at 3 months were: LOE switchers 1.1/1.6; AE switchers 1.5/0.8. In LOE switchers, a good/moderate EULAR response was more prevalent during the second treatment course than during the first (63% versus 54%, p = 0.02). AE switchers achieved similar EULAR responses to both treatments (59% versus 50%, p = 0.38).

CONCLUSION

LOE switchers had a better clinical response to the second treatment. AE switchers responded equally well to both treatments, with a low risk of discontinuing the second drug as a result of AE. Drug survival of the switchers' second biological therapy was higher than of the first, but lower than that of non-switchers. No difference between various sequences of drugs were found. Danish post-marketing data thus support that RA patients may benefit from switching biological therapy.

摘要

目的

研究类风湿关节炎(RA)患者换用第二种生物制剂的疗效。

方法

自2000年起,丹麦接受生物治疗的RA患者(n = 1021)被登记在全国性的DANBIO数据库中。对2005年前换用治疗方案的患者(n = 235)的第一个和第二个治疗疗程进行分析,包括换用原因、疾病活动评分28(DAS28)、DAS28改善情况、欧洲抗风湿病联盟(EULAR)反应和药物生存期。大多数患者从英夫利昔单抗换用至依那西普或阿达木单抗。

结果

换用者第一个/第二个治疗疗程的中位生存期分别为37/92周(所有患者第一个治疗疗程为119周)。换用原因包括疗效不佳(LOE;109例患者)、不良事件(AE;72例)、其他原因(54例)。若患者对第一种药物出现AE,则15%的患者对第二种药物也出现AE。第一个/第二个治疗疗程3个月时DAS28的中位改善情况为:疗效不佳换用者1.1/1.6;不良事件换用者1.5/0.8。在疗效不佳换用者中,第二个治疗疗程期间良好/中等的EULAR反应比第一个疗程更普遍(63%对54%,p = 0.02)。不良事件换用者在两种治疗中的EULAR反应相似(59%对50%,p = 0.38)。

结论

疗效不佳换用者对第二种治疗有更好的临床反应。不良事件换用者对两种治疗的反应相同,因不良事件停用第二种药物的风险较低。换用者第二种生物治疗的药物生存期高于第一种,但低于未换用者。未发现不同药物顺序之间存在差异。因此,丹麦的上市后数据支持RA患者可能从换用生物治疗中获益。

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