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.
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.
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DOI：
10.1136/rmdopen-2017-000491
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发表时间：
2017
期刊：
影响因子：
6.2
通讯作者：
van Vollenhoven RF
中科院分区：
文献类型：
--
作者：
Fleischmann R;Wollenhaupt J;Takiya L;Maniccia A;Kwok K;Wang L;van Vollenhoven RF
托法替尼是一种口服Janus激酶抑制剂，用于治疗类风湿性关节炎。该事后分析评价了长期扩展（LTE）研究中接受托法替尼单药治疗或联合治疗的患者，以及从单药治疗转换为联合治疗（单药→联合）或从联合治疗转换为单药治疗（联合→单药）的患者。数据汇总自开放标签LTE研究（口服Sequel（NCT 00413699;正在进行;数据收集于2016年1月14日）和NCT 00661661），涉及参与合格索引研究的患者。疗效结局包括美国流变学学会20/50/70比率、28个关节疾病活动性评分较基线的变化、红细胞沉降率（DAS 28 -4（ESR））、临床疾病活动性指数（CDAI）和健康评估能力-残疾指数以及DAS 28 -4（ESR）和CDAI低疾病活动性和缓解。安全性评估超过96个月。在接受治疗的4967例患者中，35.4%开始托法替尼单药治疗，64.6%开始联合治疗，2.6%为单药→联合治疗转换者，7.1%为联合治疗→单药转换者。多次转换的患者被排除在外。在开始单药治疗和联合治疗的受试者中，87.8%（1543/1757）和82.0%（2631/3210）的受试者在整个研究期间保持相同的方案;疗效得以维持。托法替布5 mg和10 mg每日两次治疗的严重不良事件发生率（IR）分别为9.42和8.41（单药治疗），8.36和10.75（联合治疗）;因AE停药的IR分别为7.13和6.06（单药治疗），7.82和8.06（联合治疗）（重叠CI）。对于单药→联合用药和联合用药→单药转换者，在转换后30天内因AE而停药的比例分别为0.8%和0.9%。托法替尼作为单药治疗或联合治疗的疗效维持至第48个月，并持续至第72个月，治疗方案的转换最少。安全性在96个月内保持一致。NCT 00413699（预结果）和NCT 00661661（结果）。
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. 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. 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. 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. NCT00413699 (Pre-results) and NCT00661661 (Results).