Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA.
Seoul National University, Seoul, Republic of Korea.
Clin Rheumatol. 2018 Aug;37(8):2043-2053. doi: 10.1007/s10067-018-4077-3. Epub 2018 Apr 14.
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. We evaluated the relationship between disease activity, according to Routine Assessment of Patient Index Data 3 (RAPID3) after 6-month treatment with tofacitinib, and long-term outcomes at 24 months. This was a post hoc analysis of two 24-month, phase 3, randomized controlled trials in methotrexate (MTX)-naïve (ORAL Start [NCT01039688]) or MTX-inadequate responder patients (ORAL Scan [NCT00847613]) receiving tofacitinib 5 or 10 mg twice daily (BID) as monotherapy or with background MTX. RAPID3 scores were calculated at baseline, month (M)6, and M24, and defined as remission (≤ 3), low (LDA; > 3-≤ 6), moderate (MDA; > 6-≤ 12), or high disease activity (HDA; > 12). Clinical Disease Activity Index (CDAI), Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, and radiographic non-progression (modified Total Sharp Scores ≤ 0) at M24 were evaluated by M6 RAPID3 response. Among patients receiving tofacitinib 5 or 10 mg BID, respectively, 42.2 and 51.5% (ORAL Start) and 29.8 and 39.0% (ORAL Scan) achieved RAPID3 remission/LDA at M6. Most patients maintained/improved RAPID3 responses at M24. A higher proportion of patients in RAPID3 remission/LDA versus MDA/HDA at M6 achieved CDAI remission, reported normative HAQ-DI scores (< 0.5), and achieved both normative HAQ-DI scores and radiographic non-progression at M24. Patients achieving RAPID3 remission/LDA after 6-month treatment with tofacitinib 5 or 10 mg BID have improved long-term outcomes versus patients with MDA/HDA. These findings support the use of RAPID3 to monitor longer-term disease activity in conjunction with physician-assessed measures.
托法替布是一种用于治疗类风湿关节炎的口服 Janus 激酶抑制剂。我们评估了托法替布治疗 6 个月后根据常规评估患者数据 3(RAPID3)评估的疾病活动度与 24 个月时的长期结果之间的关系。这是两项为期 24 个月、随机对照的 3 期临床试验(MTX 初治(ORAL Start [NCT01039688])或 MTX 应答不足的患者(ORAL Scan [NCT00847613])的事后分析,患者接受托法替布 5 或 10mg 每日两次(BID)作为单药治疗或联合背景 MTX。在基线、第 6 个月(M)和第 24 个月(M)时计算 RAPID3 评分,并定义为缓解(≤3)、低疾病活动度(LDA;>3-≤6)、中度疾病活动度(MDA;>6-≤12)或高疾病活动度(HDA;>12)。在第 24 个月时,通过 M6 RAPID3 反应评估临床疾病活动度指数(CDAI)、健康评估问卷残疾指数(HAQ-DI)评分和放射影像学非进展(改良总 Sharp 评分≤0)。分别接受托法替布 5 或 10mg BID 的患者中,ORAL Start 组和 ORAL Scan 组分别有 42.2%和 51.5%(ORAL Start)和 29.8%和 39.0%(ORAL Scan)在 M6 时达到 RAPID3 缓解/LDA。大多数患者在 M24 时保持/改善了 RAPID3 反应。在 M6 时达到 RAPID3 缓解/LDA 的患者中,与 MDA/HDA 相比,达到 CDAI 缓解、报告正常 HAQ-DI 评分(<0.5)和达到正常 HAQ-DI 评分和放射影像学非进展的患者比例更高。接受托法替布 5 或 10mg BID 治疗 6 个月后达到 RAPID3 缓解/LDA 的患者与 MDA/HDA 患者相比,具有更好的长期结局。这些发现支持使用 RAPID3 与医生评估的措施一起监测更长期的疾病活动度。