托法替布治疗溃疡性结肠炎患者的研究：3 期随机对照诱导和维持研究中的健康相关生活质量。
Tofacitinib in Patients with Ulcerative Colitis: Health-Related Quality of Life in Phase 3 Randomised Controlled Induction and Maintenance Studies.
机构信息
Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain.
Department of Gastroenterology, University Hospitals Leuven, Leuven, Belgium.
出版信息
J Crohns Colitis. 2018 Jan 24;12(2):145-156. doi: 10.1093/ecco-jcc/jjx133.
BACKGROUND AND AIMS
Tofacitinib is an oral, small molecule Janus kinase [JAK] inhibitor that is being investigated for ulcerative colitis [UC]. We evaluated health-related quality of life [HRQoL] in tofacitinib UC Phase 3 studies.
METHODS
Patients ≥ 18 years old in OCTAVE Induction 1 [N = 598] and 2 [N = 541] with moderately to severely active UC were randomised [1:4] to placebo or tofacitinib 10 mg twice daily [BID] for 8 weeks. Subsequently, OCTAVE Sustain re-randomised [1:1:1] clinical responders [N = 593] from induction studies to placebo, tofacitinib 5 mg BID, or 10 mg BID, for 52 weeks. Inflammatory Bowel Disease Questionnaire [IBDQ] and SF-36v2® Health Survey [SF-36v2] assessed HRQoL.
RESULTS
In OCTAVE Induction 1 and 2, mean changes from baseline IBDQ were greater with tofacitinib 10 mg BID at Week 8 [28.9 and 31.5] versus placebo [15.4 and 17.2; p < 0.0001]; mean changes from baseline SF-36v2 Physical and Mental Component Summaries [PCS/MCS] were also greater with 10 mg BID [PCS: 6.8 and 6.8; MCS: 6.8 and 7.6] versus placebo [PCS: 2.5 and 4.6; MCS: 3.5 and 4.4; p < 0.01]. In OCTAVE Sustain atWeek 52, changes in IBDQ were maintained with tofacitinib 5 mg [-1.3] and 10 mg BID [0.6], and larger with placebo [-20.2; p < 0.0001]. Changes in SF-36v2 PCS/MCS were also maintained with 5 mg [PCS: 0.0; MCS: -1.0] and 10 mg BID [PCS: 0.3; MCS: 0.1] versus placebo [PCS: -5.2; MCS: -6.7; p < 0.0001] at Week 52 in OCTAVE Sustain.
CONCLUSIONS
Tofacitinib 10 mg BID induction therapy significantly improved HRQoL versus placebo at Week 8. Improvements were maintained through 52 weeks' maintenance therapy with tofacitinib 5 mg and 10 mg BID.
CLINICALTRIALS.GOV REGISTRATION NUMBERS: NCT01465763, NCT01458951 and NCT01458574.
背景和目的
托法替布是一种口服小分子 Janus 激酶 [JAK] 抑制剂，正在研究溃疡性结肠炎 [UC]。我们评估了托法替布 UC 期 3 研究中的健康相关生活质量 [HRQoL]。
方法
OCTAVE 诱导研究 1 [N = 598]和 2 [N = 541]中年龄≥18 岁、中重度活动性 UC 患者随机分为安慰剂或托法替布 10 mg 每日 2 次 [BID] 治疗 8 周。随后，OCTAVE 维持研究中，诱导研究的临床应答者 [N = 593]重新随机分为安慰剂、托法替布 5 mg BID 或 10 mg BID，治疗 52 周。炎症性肠病问卷 [IBDQ] 和 SF-36v2®健康调查 [SF-36v2] 评估 HRQoL。
结果
在 OCTAVE 诱导研究 1 和 2 中，托法替布 10 mg BID 在第 8 周时 IBDQ 的平均变化明显大于安慰剂 [28.9 和 31.5] 与安慰剂 [15.4 和 17.2；p <0.0001]；托法替布 10 mg BID 时 SF-36v2 身体和心理成分综合评分 [PCS/MCS] 的平均变化也更大 [PCS：6.8 和 6.8；MCS：6.8 和 7.6] 与安慰剂 [PCS：2.5 和 4.6；MCS：3.5 和 4.4；p <0.01]。在 OCTAVE 维持研究中，托法替布 5 mg [-1.3] 和 10 mg BID [0.6] 的 IBDQ 变化在第 52 周时得到维持，而安慰剂的变化[-20.2] 与安慰剂相比差异有统计学意义（p <0.0001）。托法替布 5 mg [PCS：0.0；MCS：-1.0] 和 10 mg BID [PCS：0.3；MCS：0.1] 的 SF-36v2 PCS/MCS 变化在第 52 周时也得到维持，与安慰剂相比差异有统计学意义 [PCS：-5.2；MCS：-6.7；p <0.0001]。
结论
托法替布 10 mg BID 诱导治疗在第 8 周时与安慰剂相比显著改善了 HRQoL。托法替布 5 mg 和 10 mg BID 的维持治疗可维持 52 周的疗效。
临床试验注册编号
NCT01465763、NCT01458951 和 NCT01458574。
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