合用DMARDs对持续抗TNF治疗的类风湿关节炎患者的影响:来自英国风湿病生物制剂注册系统的结果

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Ann Rheum Dis doi:10.1136/ard.2010.139774 Impact of concomitant use of DMARDs on the persistence with anti-TNF therapies in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register   1.       Moetaza M Soliman1, 2.       Darren M Ashcroft1, 3.       Kath D Watson2, 4.       Mark Lunt2, 5.       Deborah P M Symmons2, 6.       Kimme L Hyrich2, 7.       on behalf of the British Society for Rheumatology Biologics Register + Author Affiliations 1.       1School of Pharmacy and Pharmaceutical Sciences, The University of Manchester, Manchester, UK 2.       2Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, UK 1.       Correspondence to Dr Kimme L Hyrich, Arthritis Research UK Epidemiology Unit, Manchester Academic Health Sciences Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK; Kimme.hyrich@manchester.ac.uk Accepted 1 November 2010 Published Online First 17 February 2011 Abstract Objective To evaluate the effect of different concomitant disease modifying antirheumatic drugs (DMARDs) on the persistence with antitumour necrosis factor (anti-TNF) therapies in patients with rheumatoid arthritis (RA). Method This analysis included 10 396 patients with RA registered with the British Society for Rheumatology Biologics Register, a prospective observational cohort study, who were starting their first anti-TNF therapy and were receiving one of the following DMARD treatments at baseline: no DMARD (n=3339), methotrexate (MTX) (n=4418), leflunomide (LEF) (n=610), sulfasalazine (SSZ) (n=308), MTX+SSZ (n=902), MTX+ hydroxychloroquine (HCQ) (n=401) or MTX+SSZ+HCQ (n=418). Kaplan–Meier survival analysis was used to study the persistence with anti-TNF therapy in each DMARD subgroup up to 5 years. Multivariate Cox proportional hazard models, stratified by anti-TNF used and start year and adjusted for a number of potential confounders, were used to compare treatment persistence overall and according to the reason for discontinuation between each of the DMARD subgroups, using MTX as reference. Results One-year drug survival (95% CI) for the first anti-TNF therapy was 71% (71% to 72%) but this dropped to 42% (41% to 43%) at 5 years. Compared with MTX, patients receiving no DMARD, LEF or SSZ were more likely to discontinue their first anti-TNF therapy while patients receiving MTX in combination with other DMARDs showed better treatment persistence. Conclusions These results support the continued use of background DMARD combinations which include MTX. Consideration should be given to the discontinuation of LEF and SSZ monotherapy at the time anti-TNF therapies are started, with the possible exception of the SSZ+ETN combination.

合用DMARDs对持续抗-TNF治疗的类风湿关节炎患者的影响:来自英国风湿病生物制剂注册系统的结果   目的 探讨不同疾病缓解药物(DMARDs) 的伴随应用对类风湿关节炎(RA)患者持续应用抗肿瘤坏死因子(anti-TNF)的的影响。   方法 该分析是一项前瞻、观察队列研究，包括了10 396例英国风湿病生物制剂注册系统的患者，这些患者在首次抗-TNF治疗基线时同时接受下列DMARD的治疗:无DMARD(n = 3339),甲氨蝶呤(MTX)(n = 4418),来氟米特(LEF)(n = 610),柳氮磺氨吡啶(SSZ)(n = 308),MTX+ SSZ(n = 902),MTX+羟基氯喹(HCQ)(n = 401)或MTX + SSZ + HCQ(n = 418名)。Kaplan-Meier生存分析研究了持续抗-TNF联合不同DMARD治疗长达五年时间。多变量Cox比例风险模型,按照anti-TNF使用和起始年并校正多种潜在的混杂因素,以MTX为对照对总的持续治疗时间和不同DMARD组间停药的原因作出比较。     结果 首个抗-TNF治疗的一年药物维持率为71%(95%CI 71%-72%),但第5年时下降到42%(41%-43%)。与氨甲蝶呤(MTX)相比,不用DMARD,用LEF或SSZ更容易停用其首个抗-TNF治疗，而MTX与其他DMARDs联用组则显示出更好地治疗持续性。 结论:这些结果支持包括MTX在内的DMARD联合持续应用。应考虑到SSZ或 LEF单药可导致初始抗-TNF的停用,而SSZ + ETN的组合则可能是个例外。