NEJM：新药Tofacitinib具有治疗类风湿性关节炎的疗效

Tofacitinib结构式，图片来自维基共享资源。

在一项新研究中，包括来自瑞典卡罗林斯卡研究所(Karolinska Institutet)研究人员在内的一个研究小组证实一种被称作Tofacitinib的新药治疗类风湿性关节炎(rheumatoid arthritis)的疗效。根据这项发表在The New England Journal of Medicine期刊上的研究，这种药物正好与生物药物一样有效，但是与生物制品不同的是，它能够作为片剂的形式被人们服用。

这项研究是Tofacitinib的第三期临床试验，涉及717名类风湿性关节炎患者。这些试验参与者被分成三组：服用高剂量或低剂量的Tofacitinib；服用已被批准上市的生物药物阿达木单抗(Adalimumab)；服用安慰剂。

根据美国风湿病学会发布的ACR20标准，6个月之后，服用Tofacitinib的患者表现出最为显著性的改善。服用Tofacitinib的患者中50%以上的人减轻了一些症状，而服用阿达木单抗的患者和服用安慰剂的患者当中分别有47%和27%的人是这样的。

这一发现证实新物质Tofacitinib在疗效上等同于生物药物，而且它非常令人关注，这是因为人们需要一种更加有效的药物来治疗类风湿性关节炎。

这项研究也证实服用Tofacitinib有风险产生几种可能的副作用，包括肠胃失调、肝病、红细胞与白细胞数量下降、胆固醇水平上升和对感染敏感性增加。不过，这些副作用当中没有一个是比较常见的，因此，大多数患者对这种药物治疗耐受性良好。

本文编译自Study shows efficacy of new rheumatoid arthritis drug

doi: 10.1056/NEJMoa1112072
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Tofacitinib or Adalimumab versus Placebo in Rheumatoid Arthritis

Ronald F. van Vollenhoven, M.D., Roy Fleischmann, M.D., Stanley Cohen, M.D., Eun Bong Lee, M.D., Ph.D., Juan A. García Meijide, M.D., Sylke Wagner, M.D., Sarka Forejtova, M.D., Samuel H. Zwillich, M.D., David Gruben, Ph.D., Tamas Koncz, M.D., Gene V. Wallenstein, Ph.D., Sriram Krishnaswami, Ph.D., John D. Bradley, M.D., and Bethanie Wilkinson, Ph.D. for the ORAL Standard Investigators

BACKGROUND Tofacitinib (CP-690,550) is a novel oral Janus kinase inhibitor that is being investigated for the treatment of rheumatoid arthritis. METHODS In this 12-month, phase 3 trial, 717 patients who were receiving stable doses of methotrexate were randomly assigned to 5 mg of tofacitinib twice daily, 10 mg of tofacitinib twice daily, 40 mg of adalimumab once every 2 weeks, or placebo. At month 3, patients in the placebo group who did not have a 20% reduction from baseline in the number of swollen and tender joints were switched in a blinded fashion to either 5 mg or 10 mg of tofacitinib twice daily; at month 6, all patients still receiving placebo were switched to tofacitinib in a blinded fashion. The three primary outcome measures were a 20% improvement at month 6 in the American College of Rheumatology scale (ACR 20); the change from baseline to month 3 in the score on the Health Assessment Questionnaire–Disability Index (HAQ-DI) (which ranges from 0 to 3, with higher scores indicating greater disability); and the percentage of patients at month 6 who had a Disease Activity Score for 28-joint counts based on the erythrocyte sedimentation rate (DAS28-4[ESR]) of less than 2.6 (with scores ranging from 0 to 9.4 and higher scores indicating greater disease activity). RESULTS At month 6, ACR 20 response rates were higher among patients receiving 5 mg or 10 mg of tofacitinib (51.5% and 52.6%, respectively) and among those receiving adalimumab (47.2%) than among those receiving placebo (28.3%) (P<0.001 for all comparisons). There were also greater reductions in the HAQ-DI score at month 3 and higher percentages of patients with a DAS28-4(ESR) below 2.6 at month 6 in the active-treatment groups than in the placebo group. Adverse events occurred more frequently with tofacitinib than with placebo, and pulmonary tuberculosis developed in two patients in the 10-mg tofacitinib group. Tofacitinib was associated with an increase in both low-density and high-density lipoprotein cholesterol levels and with reductions in neutrophil counts. CONCLUSIONS In patients with rheumatoid arthritis receiving background methotrexate, tofacitinib was significantly superior to placebo and was numerically similar to adalimumab in efficacy. (Funded by Pfizer; ORAL Standard ClinicalTrials.gov number, NCT00853385.)