Background: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This study assessed the efficacy and safety of tofacitinib in Chinese patients with RA enrolled in Phase 3 and long-term extension (LTE) studies.
Methods: ORAL Sync was a 1-year, randomized, placebo-controlled, Phase 3 trial. Patients received tofacitinib 5 or 10 mg twice daily (BID) or placebo advanced to tofacitinib 5 or 10 mg BID at 3 or 6 months. All patients remained on ≥1 background conventional synthetic disease-modifying antirheumatic drug. ORAL Sequel is an open-label LTE study (data-cut: March 2015; data collection and analyses were ongoing, and study database was not locked at the time of analysis; study was closed in 2017). Efficacy outcomes: American College of Rheumatology (ACR) 20/50/70 response rates and Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-4 [ESR]). Patient- and physician-reported outcomes: Health Assessment Questionnaire-Disability Index (HAQ-DI), Patient and Physician Global Assessment of Arthritis, and pain (visual analog scale). Safety was assessed throughout.
Results: ORAL Sync included 218 patients; 192 were subsequently enrolled into ORAL Sequel. In ORAL Sync, more patients achieved ACR20 (tofacitinib 5 mg BID, 67.4%; 10 mg BID, 70.6%; placebo, 34.1%) and DAS28-4 (ESR) <2.6 (tofacitinib 5 mg BID, 7.1%; 10 mg BID, 13.1%; placebo, 2.3%) with tofacitinib versus placebo at Month 6. Mean changes from baseline in HAQ-DI were greater with tofacitinib versus placebo at Month 6. In ORAL Sequel, efficacy was consistent to Month 48. Incidence rates for adverse events of special interest in tofacitinib-treated patients were similar to the global population.
Conclusions: Tofacitinib significantly reduced signs/symptoms and improved physical function and quality of life in Chinese patients with moderate-to-severely active RA up to Month 48. The safety profile was consistent with the global population.
Clinical trial identifier: NCT00856544 and NCT00413699.
托法替布治疗中国类风湿关节炎患者的疗效和安全性分析 摘要 背景：托法替布是一种治疗类风湿关节炎(RA)口服Janus 激酶(Jak)抑制剂。我们通过3期临床研究以及长期拓展（LTE）研究，评估托法替布在中国RA患者中的疗效和安全性。 方法：ORAL Sync研究是一项为期1年随机双盲安慰剂对照3期临床研究。药物治疗组分别为托法替布5mg 每日两次（BID）或10mg BID；安慰剂对照组在3个月或6个月的时候随机转换成托法替布5mg BID或10mg BID。所有患者均联合使用≥合种csDMARDs治疗。ORAL Sequel是一个开放标签的LTE研究（数据截至：2015年3月；数据收集和分析同步进行；2017年研究结束）。疗效评价标准为美国风湿病学会（ACR）20/50/70应答率和DAS28-4[ESR]评分。患者/医生报告结果评价标准为健康评估调查问卷功能障碍指数（HAQ-DI），患者和医生总体评价，和疼痛（视觉模拟量表）。安全性评估贯穿整个研究。 结果：ORAL Sync研究共纳入218例RA患者，192例患者随后进入ORAL Sequel研究。ORAL Sync研究中，药物治疗组的6个月时的疗效显著高于安慰剂组，其中ACR20（托法替布5 mg BID，67.4%；10 mg BID，70.6%；安慰剂，34.1%），DAS28 -4（ESR）＜2.6（托法替布5 mg BID，7.1%；10mg BID，13.1%；安慰剂，2.3%）。同样托法替布治疗组6个月HAQ-DI的平均变化显著高于安慰剂组。ORAL Sequel研究中，疗效稳定长达48个月。安全性方面，托法替布治疗中国RA患者特别关注的不良事件发生率与全球人口相似。 结论：托法替布显著降低中国中重度活动性RA患者的症状和体征，显著改善患者生理功能和生活质量，疗效稳定长达48个月。安全性数据与全球人口一致。.
Keywords: Clinical Efficacy; Patient-Reported Outcomes; Rheumatoid Arthritis; Safety; Tofacitinib.