Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial
Tofacitinib withdrawal and retreatment in moderate-to-severe chronic plaque psoriasis: a randomized controlled trial
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DOI：
10.1111/bjd.13551
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发表时间：
2015-05-01
影响因子：
10.3
通讯作者：
Wolk, R.
中科院分区：
文献类型：
--
作者：
Bissonnette, R.;Iversen, L.;Wolk, R.
背景 托法替布是一种口服 Janus 激酶抑制剂，正在研究用于治疗中重度斑块型银屑病。目的 比较托法替布停药后的结果与继续使用的结果。方法 在这项 3 期研究 (NCT01186744) 中，患者接受托法替布 5 mg (n = 331) 或 10 mg (n = 335)，每天两次，持续 24 周。银屑病面积和严重性指数 (PASI 75) 评分较基线降低 >= 75% 且医生整体评估 (PGA) 为“清除”或“几乎清除”（PGA 反应）的患者接受安慰剂（停药）或先前剂量。复发时（初始治疗期间 PASI 改善减少 > 50%）或第 40 周，患者接受初始剂量。 结果 初始治疗：托法替布 5 毫克和 10 毫克每天两次，分别有 33.5% 和 55.2% 的患者达到 PASI 75 和 PGA 缓解，使他们符合治疗停药期的条件。停药：每天两次托法替布 5、10 mg、安慰剂 (5 mg) 和安慰剂 (10 mg) 分别有 56.2%、62.3%、23.3% 和 26.1% 维持 PASI 75 反应； 49.9%、63.9%、22.9% 和 18.0% 维持 PGA 反应； 92.3%、93.0%、32.8%和42.9%没有复发。初始治疗后低密度脂蛋白胆固醇水平升高（平均增加：5 mg每天两次，平均增加8.71 mg dL(-1)，10 mg每天两次，平均增加10.26 mg dL(-1)，停药后出现逆转。再治疗：16周后，36.8%和61.0%的复发患者使用托法替布5或10 mg达到PASI 75缓解； 44.8% 和 57.1% 恢复了 PGA 反应。 结论 与安慰剂接受者相比，接受持续治疗的患者更有效地维持了反应。连续治疗组和再治疗组的安全性相当。在那些复发的患者中，高达 60% 的患者对托法替布重新产生了反应。
Background Tofacitinib is an oral Janus kinase inhibitor being investigated for the treatment of moderate-to-severe plaque psoriasis.Objectives To compare outcomes following tofacitinib withdrawal with outcomes of continuation.Methods In this phase 3 study (NCT01186744), patients received tofacitinib 5 mg (n = 331) or 10 mg (n = 335) twice daily for 24 weeks. The patients who achieved both >= 75% reduction in Psoriasis Area and Severity Index (PASI 75) score from baseline and Physician's Global Assessment (PGA) of 'clear' or 'almost clear' (PGA response) received a placebo (withdrawal) or the previous dose. At relapse (> 50% reduction in the PASI improvement during initial treatment) or week 40, the patients received the initial dose.Results Initial treatment: 33.5% and 55.2% achieved both PASI 75 and PGA responses with tofacitinib 5 and 10 mg twice daily, respectively, making them eligible for the treatment-withdrawal period. Withdrawal: 56.2%, 62.3%, 23.3% and 26.1% maintained PASI 75 responses with tofacitinib 5, 10 mg, placebo (5 mg) and placebo (10 mg) twice daily, respectively; 49.9%, 63.9%, 22.9% and 18.0% maintained PGA responses; and 92.3%, 93.0%, 32.8% and 42.9% did not relapse. Elevations in low-density lipoprotein-cholesterol levels following initial treatment (mean increase: 8.71 mg dL(-1) with 5 mg twice daily, 10.26 mg dL(-1) with 10 mg twice daily) were reversed upon withdrawal. Retreatment: 36.8% and 61.0% of patients who relapsed achieved PASI 75 responses with tofacitinib 5 or 10 mg after 16 weeks; 44.8% and 57.1% regained PGA responses.Conclusions Patients who received continuous treatment maintained a response more effectively when compared with placebo recipients. Safety profiles were comparable in both the continuous treatment group and retreatment group. Of those patients who relapsed, up to 60% recaptured a response with tofacitinib.