Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy - A randomized, placebo-controlled, 52-week trial
Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy - A randomized, placebo-controlled, 52-week trial
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DOI：
10.1002/art.20217
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发表时间：
2004-05-01
影响因子：
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通讯作者：
Chartash, EK
中科院分区：
文献类型：
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作者：
Keystone, EC;Kavanaugh, AF;Chartash, EK
目标。肿瘤坏死因子(TNF)是一种重要的促炎细胞因子，在类风湿关节炎(RA)的炎症滑膜和关节基质降解中起重要作用。我们观察了人源性抗肿瘤坏死因子单抗阿达利单抗在活动期类风湿关节炎患者应用甲氨蝶呤(MTX)联合治疗时抑制关节结构损害、减轻症状和改善身体功能的作用。在这项为期52周的多中心、双盲、安慰剂对照研究中，619名对MTX反应不足的活动期RA患者被随机分成三组，每隔一周皮下注射阿达利单抗40毫克(n=207)，每周皮下注射阿达利单抗20毫克(n=212)，或安慰剂(n=200)加MTX。主要疗效终点是52周的放射学进展(改良方法的总夏普评分[TSS])，24周的临床反应(美国风湿病学会核心标准[ACR20]改善至少20%)，以及52周的身体功能(健康评估问卷的残疾指数[HAQ])。在第52周，接受Adali-mumab治疗的患者每隔一周接受40毫克(平均+/-SD变化0.1%+/-4.8%)或每周20 mg(0.8%+/-4.9%)的放射学进展显著低于安慰剂组(2.7%+/-6.8%)(每次比较P<或等于0.001)。此外，TSS的各组成部分在统计上也有显著变化。24周时，每隔一周服用40毫克阿达利玛单抗和每周服用20毫克阿达利玛单抗的患者中，分别有63%和61%的患者对ACR20有反应，而安慰剂组的患者只有30%(每次比较P均小于或等于0.001)。在52周时，每隔一周服用40毫克阿达利玛单抗和每周服用20毫克阿达利玛单抗的患者分别有59%和55%的患者有ACR20反应，而服用安慰剂的患者有24%的患者有反应(每一比较P<或等于0.001)。52周时，与安慰剂相比，每隔一周服用40 mg阿达利玛单抗和每周服用20 mg阿达利玛单抗的患者身体功能有显著改善(HAQ评分平均变化分别为-0.59和-0.61，分别为-0.25%和-0.25%；每次比较P<或等于0.001)。共有467名患者(75.4%)完成了52周的治疗。阿达利单抗总体耐受性良好。在接受阿达利玛单抗治疗的患者中，有22.0%的患者发生了停药，在接受安慰剂治疗的患者中，有30.0%的患者出现了中断。不良事件的发生率(严重和非严重)在阿达利单抗组和安慰剂组中相似，尽管接受阿达利马单抗治疗的患者报告严重感染的比例(3.8%)高于接受安慰剂治疗的患者(0.5%)(P<或等于0.02)，且每隔一周接受40 mg治疗的患者报告的严重感染比例最高。在这项为期52周的试验中，阿达利单抗在抑制对MTX不完全反应的活动期类风湿关节炎患者的结构性关节损害的进展、减少体征和症状以及改善身体功能方面比安慰剂更有效。
Objective. Tumor necrosis factor (TNF) is an important proinflammatory cytokine that mediates inflammatory synovitis and articular matrix degradation in rheumatoid arthritis (RA). We investigated the ability of adalimumab, a human anti-TNF monoclonal antibody, to inhibit the progression of structural joint damage, reduce the signs and symptoms, and improve physical function in patients with active RA receiving concomitant treatment with methotrexate (MTX).Methods. In this multicenter, 52-week, doubleblind, placebo-controlled study, 619 patients with active RA who had an inadequate response to MTX were randomized to receive adalimumab 40 mg subcutaneously every other week (n = 207), adalimumab 20 mg subcutaneously every week (n = 212), or placebo (n = 200) plus concomitant MTX. The primary efficacy end points were radiographic progression at week 52 (total Sharp score by a modified method [TSS]), clinical response at week 24 (improvements of at least 20% in the American College of Rheumatology core criteria [ACR20]), and physical function at week 52 (disability index of the Health Assessment Questionnaire [HAQ]).Results. At week 52, there was statistically significantly less radiographic progression, as measured by the change in TSS, in the patients receiving adali-mumab either 40 mg every other week (mean +/- SD change 0.1 +/- 4.8) or 20 mg weekly (0.8 +/- 4.9) as compared with that in the placebo group (2.7 +/- 6.8) (P less than or equal to 0.001 for each comparison). In addition, there were statistically significant changes in the components of the TSS. At week 24, ACR20 responses were achieved by 63% and 61% of patients in the adalimumab 40 mg every other week and 20 mg weekly groups, respectively, versus 30% of patients in the placebo group (P less than or equal to 0.001 for each comparison). At week 52, ACR20 responses were achieved by 59% and 55% of patients taking adalimumab 40 mg every other week and 20 mg weekly, respectively, versus 24% of patients taking placebo (P less than or equal to 0.001 for each comparison). At week 52, physical function as measured by the HAQ demonstrated statistically significant improvement with adalimumab 40 mg every other week and 20 mg weekly compared with placebo (mean change in HAQ score -0.59 and -0.61, respectively, versus -0.25; P less than or equal to 0.001 for each comparison). A total of 467 patients (75.4%) completed 52 weeks of treatment. Adalimumab was generally well tolerated. Discontinuations occurred in 22.0% of adalimumab-treated patients and in 30.0% of placebo-treated patients. The rate of adverse events (both serious and nonserious) was comparable in the adalimumab and placebo groups, although the proportion of patients reporting serious infections was higher in patients receiving adalimumab (3.8%) than in those receiving placebo (0.5%) (P less than or equal to 0.02), and was highest in the patients receiving 40 mg every other week.Conclusion. In this 52-week trial, adalimumab was more effective than placebo at inhibiting the progression of structural joint damage, reducing the signs and symptoms, and improving physical function in patients with active RA who had demonstrated an incomplete response to MTX.