托法替布单药治疗及联合治疗类风湿关节炎的安全性与反应维持情况：来自开放标签长期扩展研究的汇总数据分析
Safety and maintenance of response for tofacitinib monotherapy and combination therapy in rheumatoid arthritis: an analysis of pooled data from open-label long-term extension studies.
作者信息
Fleischmann Roy, Wollenhaupt Jürgen, Takiya Liza, Maniccia Anna, Kwok Kenneth, Wang Lisy, van Vollenhoven Ronald F
机构信息
Metroplex Clinical Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Schoen-Klinik Hamburg-Eilbek Teaching Hospital, University of Hamburg, Hamburg, Germany.
出版信息
RMD Open. 2017 Dec 18;3(2):e000491. doi: 10.1136/rmdopen-2017-000491. eCollection 2017.
OBJECTIVE
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. This post hoc analysis evaluated patients receiving tofacitinib monotherapy or combination therapy, as well as those who switched from monotherapy to combination therapy (mono→combo) or vice versa (combo→mono) in long-term extension (LTE) studies.
METHODS
Data were pooled from open-label LTE studies (ORAL Sequel (NCT00413699; ongoing; data collected 14 January 2016) and NCT00661661) involving patients who participated in qualifying index studies. Efficacy outcomes included American College of Rheumatology 20/50/70 rates, change from baseline in Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4(ESR)), Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire-Disability Index and DAS28-4(ESR) and CDAI low disease activity and remission. Safety was evaluated over 96 months.
RESULTS
Of the 4967 patients treated, 35.4% initiated tofacitinib monotherapy, 64.6% initiated combination therapy, 2.6% were mono→combo switchers and 7.1% were combo→mono switchers. Patients who switched multiple times were excluded. Of those who initiated monotherapy and combination therapy, 87.8% (1543/1757) and 82.0% (2631/3210), respectively, remained on the same regimen throughout the study; efficacy was maintained. Incidence rates (IRs) for serious adverse events with tofacitinib 5 mg and 10 mg twice daily, respectively, were 9.42 and 8.41 with monotherapy and 8.36 and 10.75 with combination therapy; IRs for discontinuations due to AEs were 7.13 and 6.06 with monotherapy and 7.82 and 8.06 with combination therapy (overlapping CIs). For mono→combo and combo→mono switchers, discontinuations due to AEs were experienced by 0.8% and 0.9%, respectively, within 30 days of switching.
CONCLUSION
Tofacitinib efficacy as monotherapy or combination therapy was maintained through month 48 and sustained to month 72, with minimal switching of treatment regimens. Safety was consistent over 96 months.
CLINICAL TRIAL REGISTRATION
NCT00413699 (Pre-results) and NCT00661661 (Results).
目的
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。这项事后分析评估了在长期扩展（LTE）研究中接受托法替布单药治疗或联合治疗的患者，以及那些从单药治疗转换为联合治疗（单药→联合）或反之（联合→单药）的患者。
方法
数据来自开放标签的 LTE 研究（ORAL Sequel（NCT00413699；正在进行；数据收集于 2016 年 1 月 14 日）和 NCT00661661），涉及参与合格索引研究的患者。疗效指标包括美国风湿病学会 20/50/70 缓解率、28 个关节疾病活动评分相对于基线的变化、红细胞沉降率（DAS28-4(ESR)）、临床疾病活动指数（CDAI）、健康评估问卷残疾指数以及 DAS28-4(ESR)和 CDAI 的低疾病活动度和缓解情况。安全性评估长达 96 个月。
结果
在接受治疗的 4967 名患者中，35.4%开始接受托法替布单药治疗，64.6%开始接受联合治疗，2.6%是从单药治疗转换为联合治疗的患者，7.1%是从联合治疗转换为单药治疗的患者。多次转换治疗方案的患者被排除。在开始接受单药治疗和联合治疗的患者中，分别有 87.8%（1543/1757）和 82.0%（2631/3210）在整个研究过程中维持相同的治疗方案；疗效得以维持。托法替布每日两次 5mg 和 10mg 单药治疗时严重不良事件的发生率分别为 9.42 和 8.41，联合治疗时分别为 8.36 和 10.75；因不良事件停药的发生率单药治疗时为 7.13 和 6.06，联合治疗时为 7.82 和 8.06（置信区间重叠）。对于从单药治疗转换为联合治疗和从联合治疗转换为单药治疗的患者，转换后 30 天内因不良事件停药的比例分别为 0.8%和 0.9%。
结论
托法替布单药治疗或联合治疗的疗效在第 48 个月时得以维持，并持续至第 72 个月，治疗方案的转换极少。安全性在 96 个月内保持一致。
临床试验注册
NCT00413699（预结果）和 NCT00661661（结果）。
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