Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria.
Brief Report: Remission Rates With Tofacitinib Treatment in Rheumatoid Arthritis: A Comparison of Various Remission Criteria.
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DOI：
10.1002/art.39996
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Mebus C
中科院分区：
文献类型：
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作者：
Smolen JS;Aletaha D;Gruben D;Zwillich SH;Krishnaswami S;Mebus C
托法替尼是一种口服JAK抑制剂，用于治疗类风湿性关节炎（RA）。在既往托法替尼临床试验中，使用基于28个关节疾病活动性评分（DAS 28）的分析评估结局。在这项研究中，根据各种缓解标准，在5项III期随机对照研究中评价了缓解率。在所有5项研究中，托法替尼以5 mg每日2次或10 mg每日2次的剂量给药，作为单药治疗或与背景甲氨蝶呤或其他常规合成的疾病缓解抗风湿药物联合给药。其中一项研究包括阿达木单抗40 mg，每2周一次。除了使用红细胞沉降率（DAS 28 - 4 [ESR]）的4变量DAS 28（III期研究中使用的主要疗效变量）外，还使用C反应蛋白水平（DAS 28 - 4 [CRP]）、临床疾病活动指数（CDAI）、简化疾病活动指数（SDAI）和基于布尔的评估通过4变量DAS 28事后评估疾病活动性。共分析了3，306例患者（其中1，213例患者接受托法替布5 mg每日两次，1，212例患者接受托法替布10 mg每日两次，679例患者接受安慰剂，202例患者接受阿达木单抗40 mg每2周一次）。缓解率根据所使用的标准而有所不同，活性治疗组中DAS 28 - 4（CRP）的缓解率高于其他评分。第3个月时，使用DAS 28 - 4（CRP）、DAS 28 - 4（ESR）、SDAI、CDAI和基于布尔的方法，托法替布5 mg每日2次的缓解率分别为18 - 22%、5 - 10%、4 - 7%、5 - 6%和2 - 7%。相比之下，安慰剂组的缓解率为0%-7%，DAS 28 - 4（ESR）和DAS 28 - 4（CRP）之间的差异较小。尽管与安慰剂相比，托法替布5 mg每日两次和10 mg每日两次剂量在实现疾病缓解方面有效，但无论疾病活动性指标如何，使用DAS 28 - 4（CRP）时的缓解率均显著较高。缓解标准中急性期反应物的存在或不存在以及类型是各治疗组缓解率的重要贡献因素。这一发现对试验设计和临床实践具有重要意义。
Tofacitinib is an oral JAK inhibitor that is used for the treatment of rheumatoid arthritis (RA). In previous clinical trials of tofacitinib, a Disease Activity Score in 28 joints (DAS28)–based analysis was used to assess outcomes. In this study, remission rates according to various remission criteria were evaluated across 5 phase III randomized controlled studies. In all 5 studies, tofacitinib was administered at a dosage of 5 mg twice daily or 10 mg twice daily, either as monotherapy or with background methotrexate or other conventional synthetic disease‐modifying antirheumatic drugs. One of the studies included adalimumab 40 mg once every 2 weeks. In addition to the 4‐variable DAS28 using the erythrocyte sedimentation rate (DAS28‐4[ESR]), a primary efficacy variable used in the phase III studies, disease activity was assessed post hoc by the 4‐variable DAS28 using the C‐reactive protein level (DAS28‐4[CRP]), the Clinical Disease Activity Index (CDAI), the Simplified Disease Activity Index (SDAI), and Boolean‐based assessment. A total of 3,306 patients were analyzed (1,213 of these patients received tofacitinib 5 mg twice daily, 1,212 received tofacitinib 10 mg twice daily, 679 received placebo, and 202 received adalimumab 40 mg every 2 weeks). Remission rates varied according to the criteria used, with higher rates in the active‐treatment groups for the DAS28‐4(CRP) than for other scores. At month 3, remission rates with tofacitinib 5 mg twice daily were 18–22% using the DAS28‐4(CRP), 5–10% using the DAS28‐4(ESR), 4–7% using the SDAI, 5–6% using the CDAI, and 2–7% using the Boolean‐based method. In contrast, the remission rates with placebo varied from 0% to 7%, with small differences between the DAS28‐4(ESR) and the DAS28‐4(CRP). Although tofacitinib at dosages of 5 mg twice daily and 10 mg twice daily was effective compared with placebo in achieving disease remission, regardless of the disease activity measure, remission rates were substantially higher when the DAS28‐4(CRP) was used. The presence or absence and type of acute‐phase reactants in remission criteria were significant contributors to remission rates across treatment groups. This finding has important consequences for trial design and clinical practice.