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接受阿达木单抗、依那西普或英夫利昔单抗治疗的类风湿关节炎患者的治疗反应、缓解率和药物依从性的直接比较:丹麦全国DANBIO注册中心八年临床实践监测结果

Direct comparison of treatment responses, remission rates, and drug adherence in patients with rheumatoid arthritis treated with adalimumab, etanercept, or infliximab: results from eight years of surveillance of clinical practice in the nationwide Danish DANBIO registry.

作者信息

Hetland Merete Lund, Christensen Ib Jarle, Tarp Ulrik, Dreyer Lene, Hansen Annette, Hansen Ib Tønder, Kollerup Gina, Linde Louise, Lindegaard Hanne M, Poulsen Uta Engling, Schlemmer Annette, Jensen Dorte Vendelbo, Jensen Signe, Hostenkamp Gisela, Østergaard Mikkel

机构信息

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

出版信息

Arthritis Rheum. 2010 Jan;62(1):22-32. doi: 10.1002/art.27227.

Abstract

OBJECTIVE

To compare tumor necrosis factor alpha inhibitors directly regarding the rates of treatment response, remission, and the drug survival rate in patients with rheumatoid arthritis (RA), and to identify clinical prognostic factors for response.

METHODS

The nationwide DANBIO registry collects data on rheumatology patients receiving routine care. For the present study, we included patients from DANBIO who had RA (n = 2,326) in whom the first biologic treatment was initiated (29% received adalimumab, 22% received etanercept, and 49% received infliximab). Baseline predictors of treatment response were identified. The odds ratios (ORs) for clinical responses and remission and hazard ratios (HRs) for drug withdrawal were calculated, corrected for age, disease duration, the Disease Activity Score in 28 joints (DAS28), seropositivity, concomitant methotrexate and prednisolone, number of previous disease-modifying drugs, center, and functional status (Health Assessment Questionnaire score).

RESULTS

Seventy percent improvement according to the American College of Rheumatology criteria (an ACR70 response) was achieved in 19% of patients after 6 months. Older age, concomitant prednisolone treatment, and low functional status at baseline were negative predictors. The ORs (95% confidence intervals [95% CIs]) for an ACR70 response were 2.05 (95% CI 1.52-2.76) for adalimumab versus infliximab, 1.78 (95% CI 1.28-2.50) for etanercept versus infliximab, and 1.15 (95% CI 0.82-1.60) for adalimumab versus etanercept. Similar predictors and ORs were observed for a good response according to the European League Against Rheumatism criteria, DAS28 remission, and Clinical Disease Activity Index remission. At 48 months, the HRs for drug withdrawal were 1.98 for infliximab versus etanercept (95% 1.63-2.40), 1.35 for infliximab versus adalimumab (95% CI 1.15-1.58), and 1.47 for adalimumab versus etanercept (95% CI 1.20-1.80).

CONCLUSION

Older age, low functional status, and concomitant prednisolone treatment were negative predictors of a clinical response and remission. Infliximab had the lowest rates of treatment response, disease remission, and drug adherence, adalimumab had the highest rates of treatment response and disease remission, and etanercept had the longest drug survival rates. These findings were consistent after correction for confounders and sensitivity analyses and across outcome measures and followup times.

摘要

目的

直接比较肿瘤坏死因子α抑制剂在类风湿关节炎(RA)患者中的治疗反应率、缓解率和药物生存率,并确定反应的临床预后因素。

方法

全国性的DANBIO注册机构收集接受常规护理的风湿病患者的数据。在本研究中,我们纳入了DANBIO中首次开始生物治疗的RA患者(n = 2326),其中29%接受阿达木单抗,22%接受依那西普,49%接受英夫利昔单抗。确定治疗反应的基线预测因素。计算临床反应和缓解的比值比(OR)以及药物撤药的风险比(HR),并对年龄、疾病持续时间、28个关节的疾病活动评分(DAS28)、血清阳性、同时使用甲氨蝶呤和泼尼松龙、既往疾病改善药物的数量、中心和功能状态(健康评估问卷评分)进行校正。

结果

6个月后,19%的患者根据美国风湿病学会标准实现了70%的改善(ACR70反应)。年龄较大、同时接受泼尼松龙治疗以及基线时功能状态较低是阴性预测因素。阿达木单抗与英夫利昔单抗相比,ACR70反应的OR(95%置信区间[95%CI])为2.05(95%CI 1.52 - 2.76),依那西普与英夫利昔单抗相比为1.78(95%CI 1.28 - 2.50),阿达木单抗与依那西普相比为1.15(95%CI 0.82 - 1.60)。根据欧洲抗风湿病联盟标准、DAS28缓解和临床疾病活动指数缓解的良好反应观察到类似的预测因素和OR。在48个月时,英夫利昔单抗与依那西普相比药物撤药的HR为1.98(95% 1.63 - 2.40),英夫利昔单抗与阿达木单抗相比为1.35(95%CI 1.15 - 1.58),阿达木单抗与依那西普相比为1.47(95%CI 1.20 - 1.80)。

结论

年龄较大、功能状态较低以及同时接受泼尼松龙治疗是临床反应和缓解的阴性预测因素。英夫利昔单抗的治疗反应率、疾病缓解率和药物依从性最低,阿达木单抗的治疗反应率和疾病缓解率最高,依那西普的药物生存率最长。在校正混杂因素和敏感性分析后,以及在不同结局指标和随访时间内,这些发现是一致的。

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