St Joseph's Healthcare, McMaster University, Hamilton, Ontario, Canada.
Department of Rheumatology, Cairo University, Cairo, Egypt.
J Clin Rheumatol. 2019 Apr;25(3):115-126. doi: 10.1097/RHU.0000000000000786.
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We performed a comprehensive review of phase 3 studies of tofacitinib 5 mg twice daily (BID) (approved dose in many countries) in patients with moderate to severe RA and inadequate response to prior disease-modifying antirheumatic drugs.
A search of PubMed and ClinicalTrials.gov identified 5 studies: ORAL Solo (NCT00814307), ORAL Sync (NCT00856544), ORAL Standard (included adalimumab 40 mg once every 2 weeks; NCT00853385), ORAL Scan (NCT00847613), and ORAL Step (NCT00960440). Efficacy and safety data for tofacitinib 5 mg BID, placebo, and adalimumab were analyzed.
Across the 5 studies, 1216 patients received tofacitinib 5 mg BID, 681 received placebo, and 204 received adalimumab. At month 3, tofacitinib demonstrated significantly higher 20%, 50%, and 70% improvement in American College of Rheumatology response criteria (ACR20, ACR50, and ACR70, respectively) response rates, greater improvement in Health Assessment Questionnaire-Disability Index, and a higher proportion of Disease Activity Score-defined remission than placebo. Frequencies of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar for tofacitinib and placebo at month 3; serious infection events were more frequent for tofacitinib. In ORAL Standard, although not powered for formal comparisons, tofacitinib and adalimumab had numerically similar efficacy and AEs; serious AEs and serious infection events were more frequent with tofacitinib.
Tofacitinib 5 mg BID reduced RA signs and symptoms and improved physical function versus placebo in patients with inadequate response to prior disease-modifying antirheumatic drugs. Tofacitinib 5 mg BID had a consistent, manageable safety profile across studies, with no new safety signals identified.
托法替布是一种用于治疗类风湿关节炎（RA）的口服 Janus 激酶抑制剂。我们对托法替布 5mg，每日两次（BID）（许多国家的批准剂量）治疗对先前的疾病修饰抗风湿药物反应不足的中重度 RA 患者的 3 期研究进行了全面综述。
在 PubMed 和 ClinicalTrials.gov 上进行了搜索，确定了 5 项研究：ORAL Solo（NCT00814307）、ORAL Sync（NCT00856544）、ORAL Standard（包含阿达木单抗 40mg，每 2 周 1 次；NCT00853385）、ORAL Scan（NCT00847613）和 ORAL Step（NCT00960440）。分析了托法替布 5mg BID、安慰剂和阿达木单抗的疗效和安全性数据。
在这 5 项研究中，1216 名患者接受了托法替布 5mg BID，681 名患者接受了安慰剂，204 名患者接受了阿达木单抗。在第 3 个月时，托法替布在美国风湿病学会反应标准（ACR20、ACR50 和 ACR70）的 20%、50%和 70%改善反应率、健康评估问卷残疾指数的更大改善和疾病活动评分定义的缓解率方面显著高于安慰剂。在第 3 个月时，托法替布和安慰剂的不良反应（AE）、严重 AE 和因 AE 停药的频率相似；托法替布的严重感染事件更为频繁。在 ORAL Standard 中，虽然没有进行正式比较的功效，但托法替布和阿达木单抗的疗效和 AE 相似；托法替布的严重 AE 和严重感染事件更为频繁。
托法替布 5mg BID 降低了对先前疾病修饰抗风湿药物反应不足的患者的 RA 体征和症状，并改善了身体功能。托法替布 5mg BID 在研究中具有一致的、可管理的安全性，未发现新的安全性信号。
