Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy
Improvement in patient-reported outcomes in a rituximab trial in patients with severe rheumatoid arthritis refractory to anti-tumor necrosis factor therapy
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DOI：
10.1002/art.23715
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发表时间：
2008-06-15
期刊：
影响因子：
--
通讯作者：
Jost, F.
中科院分区：
文献类型：
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作者：
Keystone, E.;Burmester, G. R.;Jost, F.
Objective.评估利妥昔单抗联合甲氨蝶呤治疗对抗肿瘤坏死因子治疗反应不足的活动性类风湿关节炎（RA）患者的疗效。活动性RA患者随机分配至利妥昔单抗组（第1天和第15天1,000 mg）或安慰剂组。主要终点是第24周时美国流变学学会应答率20%的患者比例。其他目的是通过比较组间的平均变化，评估治疗对疼痛、疲劳、功能障碍、健康相关生活质量和疾病活动的影响。在意向治疗人群中进行分析。确定在健康评估问卷（HAQ）、残疾指数（DI）、慢性疾病治疗疲劳功能评估（FACIT-F）和简明健康状况调查表（SF-36）中达到最小临床重要差异的患者比例。利妥昔单抗组的疼痛缓解程度在统计学上显著更高。从第12周至第24周，利妥昔单抗患者的FACIT-F显示出比安慰剂患者显著更大的改善。利妥昔单抗患者从第8周至第24周的功能障碍（通过HAQ DI测量）较基线的平均改善显著更大。利妥昔单抗组SF-36身体健康评分较基线的平均+/- SD变化为6.64 +/- 8.74。安慰剂组为1.48 ± 7.32（P < 0.0001）。SF-36精神健康评分较基线的平均变化，利妥昔单抗组为5.32 ± 12.41，安慰剂组为2.25 ± 12.23（P = 0.0269）。利妥昔单抗在患者报告的疼痛、疲劳、功能障碍、健康相关生活质量和疾病活动方面产生了快速、有临床意义和统计学显著的改善。这些影响在整个研究期间持续存在。
Objective. To assess the effects of treatment with rituximab plus methotrexate on patient-reported outcomes in patients with active rheumatoid arthritis (RA) who experienced inadequate response to anti-tumor necrosis factor therapy.Methods. Patients with active RA were randomly assigned to rituximab (1,000 mg on days 1 and 15) or placebo. The primary end point was the proportion of patients with an American College of Rheumatology 20% response at week 24. Additional goals were to assess treatment effects on pain, fatigue, functional disability, health-related quality of life, and disease activity by comparing mean changes between groups. The analysis was conducted in the intent-to-treat population. The proportion of patients who achieved the minimum clinically important difference on the Health Assessment Questionnaire (HAQ) disability index (DI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), and Short Form 36 (SF-36) was determined.Results. Rituximab patients had statistically significantly greater pain relief. The FACIT-F showed significantly greater improvement in rituximab patients than placebo patients from weeks 12 through 24. Mean improvement from baseline in functional disability (measured by the HAQ DI) was significantly greater in rituximab patients from weeks 8 to 24. The mean +/- SD change from baseline for the SF-36 Physical Component Score was 6.64 +/- 8.74 for rituximab. patients and 1.48 +/- 7.32 for placebo patients (P < 0.0001). The mean change from baseline for the SF-36 Mental Component Score was 5.32 +/- 12.41 for rituximab patients and 2.25 +/- 12.23 for placebo patients (P = 0.0269).Conclusion. Rituximab produced rapid, clinically meaningful, and statistically significant improvements in patient-reported pain, fatigue, functional disability, health-related quality of life, and disease activity. These effects were sustained throughout the study.