Kimball A B, Papp K A, Reich K, Gooderham M, Li Q, Cichanowitz N, La Rosa C, Blauvelt A
Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, U.S.A.
K. Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada.
Br J Dermatol. 2020 Jun;182(6):1359-1368. doi: 10.1111/bjd.18484. Epub 2019 Nov 19.
Chronic psoriasis may require medication adjustments over time.
To evaluate the efficacy/safety of tildrakizumab in subgroups from the reSURFACE studies (N = 1862) that received continuous dosing, higher/lower dosing, treatment interruption/reinitiation and initiation.
Responders [Psoriasis Area and Severity Index (PASI) ≥ 75%] and partial responders (PASI ≥ 50% to < 75%) in Part 3 of the reSURFACE studies (weeks 28-52 or week 64) who received tildrakizumab 200 mg or 100 mg were rerandomized to the same dosage (T100/T100 or T200/T200), a higher/lower dosage (T100/T200 or T200/T100) or placebo (PBO) (T100/PBO or T200/PBO). Patients receiving PBO who relapsed were reinitiated to tildrakizumab. Etanercept (ETN) week-28 partial responders and nonresponders (PASI < 50%) received tildrakizumab 200 mg (ETN/T200).
Among T100/T100 and T200/T200 week-28 partial responders, the proportion of patients who achieved as-observed PASI 75 responses increased over time. Among T100/T200 week-28 partial responders, PASI 75 responses increased from week 32 (38·5%) to week 52 (63·2%) and remained consistent in T200/T100 week-28 responders. Among patients who relapsed in the T100/PBO and T200/PBO groups, 86% and 83% of those who reinitiated tildrakizumab achieved PASI 75 by week 64, respectively. Among ETN/T200 week-28 partial responders, PASI 75 responses (nonresponder imputation) increased from week 32 (24·1%) to week 52 (74·7%). PASI 90, PASI 100 and Physician's Global Assessment responses were consistent with PASI 75 results. Treatment was well tolerated.
Patients generally fared well with tildrakizumab maintenance, reinitiation, dose adjustment or initiation. What's already known about this topic? Tildrakizumab demonstrated significant efficacy vs. placebo with a positive safety profile during the first 28 weeks of treatment in two randomized double-blind trials. What does this study add? Treatment scenarios with tildrakizumab, such as long-term continuous dosing (up to 64 weeks), treatment interruption/reinitiation and switching from another biologic, can be part of the management of plaque psoriasis with a reasonable expectation of efficacy and tolerability.
慢性银屑病可能需要随着时间推移调整用药。
评估在reSURFACE研究（N = 1862）中接受持续给药、更高/更低剂量、治疗中断/重新开始及起始治疗的亚组患者中，替拉珠单抗的疗效/安全性。
reSURFACE研究第3部分（第28 - 52周或第64周）中接受200 mg或100 mg替拉珠单抗治疗的应答者[银屑病面积和严重程度指数（PASI）≥ 75%]和部分应答者（PASI≥ 50%至< 75%）被重新随机分组，接受相同剂量（T100/T100或T200/T200）、更高/更低剂量（T100/T200或T200/T100）或安慰剂（PBO）（T100/PBO或T200/PBO）。接受PBO且复发的患者重新开始使用替拉珠单抗治疗。依那西普（ETN）治疗第28周时的部分应答者和无应答者（PASI < 50%）接受200 mg替拉珠单抗治疗（ETN/T200）。
在T100/T100和T200/T200治疗第28周时的部分应答者中，达到实际观察到的PASI 75应答的患者比例随时间增加。在T100/T200治疗第28周时的部分应答者中，PASI 75应答从第32周的38.5%增至第52周的63.2%，在T200/T100治疗第28周时的应答者中保持稳定。在T100/PBO和T200/PBO组中复发的患者中，重新开始使用替拉珠单抗治疗的患者分别有86%和83%在第64周时达到PASI 75。在ETN/T200治疗第28周时的部分应答者中，PASI 75应答（无应答者估算）从第32周的24.1%增至第52周的74.7%。PASI 90、PASI 100及医生整体评估应答与PASI 75结果一致。治疗耐受性良好。
患者在接受替拉珠单抗维持治疗、重新开始治疗、剂量调整或起始治疗时总体情况良好。关于该主题已知的信息有哪些？在两项随机双盲试验中，替拉珠单抗在治疗的前28周内与安慰剂相比显示出显著疗效且安全性良好。本研究增加了什么内容？替拉珠单抗的治疗方案，如长期持续给药（长达64周）、治疗中断/重新开始以及从另一种生物制剂转换治疗，可作为斑块状银屑病管理的一部分，疗效和耐受性有望达到合理预期。
