Arthritis Research and Care Foundation, Center for Rheumatic Diseases, Pune, India.
St. John's Medical College Hospital, Bangalore, India.
Int J Rheum Dis. 2020 Jul;23(7):882-897. doi: 10.1111/1756-185X.13853. Epub 2020 Jun 1.
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We characterized tofacitinib efficacy/safety in Indian vs rest of the world (ROW; excluding India) RA patients.
Efficacy data were pooled for disease-modified antirheumatic drug (DMARD) inadequate responders from Phase (P)3 studies. For Indian patients, ORAL Solo and ORAL Scan; ROW (excluding India), these studies plus ORAL Step, ORAL Sync, and ORAL Standard. Safety data also included ORAL Start (P3; methotrexate-naïve) and ORAL Sequel (long-term extension [LTE] study; data cut-off March 2017) for Indian patients, and these studies plus A3921041 (LTE study; Japanese study) for ROW. Efficacy outcomes at months 3/6: American College of Rheumatology (ACR)20/50/70; Disease Activity Score in 28 joints, erythrocyte sedimentation rate remission/low disease activity; change from baseline in Health Assessment Questionnaire-Disability Index. Incidence rates (IRs; patients with events/100 patient-years) for adverse events of special interest (AESIs) were assessed throughout. Descriptive data underwent no formal comparison.
One-hundred-and-ninety-seven Indian and 3879 ROW patients were included. Compared with ROW patients, Indian patients were younger, had lower body mass index, shorter RA duration, and higher baseline disease activity; most Indian patients were non-smokers and all were biologic DMARD (bDMARD)-naïve. Month 3 ACR20 rates with tofacitinib 5 mg twice daily/10 mg twice daily/placebo were 67.4%/82.1%/40.9% (India) and 59.0%/66.1%/28.2% (ROW), and month 6 rates were 76.2%/92.1%/88.9% (India) and 69.0%/74.2%/66.5% (ROW). Month 3/6 improvements in other outcomes were generally numerically greater with tofacitinib vs placebo, and similar in both populations. Compared with ROW, Indian patients had numerically fewer AEs/serious AEs, and similar IRs for discontinuations due to AEs and AESIs, except that tuberculosis (TB) IR was higher in Indian (IR = 1.21; 95% CI 0.49, 2.49) vs ROW patients (IR = 0.17; 95% CI 0.11, 0.25).
Tofacitinib efficacy/safety were similar in both populations, except TB IR, which was higher in Indian patients but in line with those in bDMARD-treated RA patients from high-risk countries (IR = 0.00-2.56; TB IR >0.05 [World Health Organization]). Limitations included the small Indian population and baseline differences between populations.
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。我们对印度与世界其他地区（ROW；不包括印度）的 RA 患者中托法替布的疗效/安全性进行了特征描述。
从 3 期研究中汇集了疾病修饰抗风湿药物（DMARD）应答不足的患者的数据。对于印度患者，为 ORAL Solo 和 ORAL Scan；ROW（不包括印度），这些研究加上 ORAL Step、ORAL Sync 和 ORAL Standard。安全性数据还包括印度患者的 ORAL Start（P3；甲氨蝶呤初治）和 ORAL Sequel（长期扩展[LTE]研究；数据截止 2017 年 3 月），以及 ROW 的 A3921041（LTE 研究；日本研究）。3/6 个月的疗效终点：美国风湿病学会（ACR）20/50/70；28 个关节疾病活动评分，红细胞沉降率缓解/低疾病活动；健康评估问卷残疾指数从基线的变化。整个过程中评估了不良事件特别关注（AESI）的不良事件发生率（IR；有事件的患者/100 患者年）。描述性数据未经正式比较。
纳入了 197 名印度患者和 3879 名 ROW 患者。与 ROW 患者相比，印度患者年龄较小，体重指数较低，RA 持续时间较短，基线疾病活动度较高；大多数印度患者不吸烟，均为生物 DMARD（bDMARD）初治患者。托法替布 5mg 每日两次/10mg 每日两次/安慰剂的第 3 个月 ACR20 率分别为 67.4%/82.1%/40.9%（印度）和 59.0%/66.1%/28.2%（ROW），第 6 个月的比率分别为 76.2%/92.1%/88.9%（印度）和 69.0%/74.2%/66.5%（ROW）。与安慰剂相比，托法替布在第 3 个月/第 6 个月的其他结局改善通常在数值上优于安慰剂，并且在两个人群中均相似。与 ROW 相比，印度患者的不良事件/严重不良事件数量较少，因不良事件和 AESI 而停药的 IR 相似，除了印度患者的结核病（TB）IR 较高（IR=1.21；95%CI 0.49，2.49），而 ROW 患者的 TBIR 较低（IR=0.17；95%CI 0.11，0.25）。
除结核病 IR 外，托法替布在两个人群中的疗效/安全性均相似，结核病 IR 在印度患者中较高，但与来自高风险国家的 bDMARD 治疗 RA 患者的 IR 一致（IR=0.00-2.56；TBIR>0.05[世界卫生组织]）。局限性包括印度患者人数较少和人群之间的基线差异。
