PDF(Pubmed)
Abstract：
Dose reduction (DR) of first-generation biologics for plaque psoriasis (TNF-alpha inhibitors (i) and interleukin (IL)-12/23i) has been described in a previous scoping review. The literature on the DR of the newest generation of biologics (IL-17/23i) was scarce. The current review provides a literature update on the previous scoping review on the DR of all biologics, including the newest generation, with a focus on the uptake and implementation of DR in practice. The current literature search on DR revealed 14 new articles in addition to those in the previous review. Four of the newly found articles tested DR strategies, mostly focusing on first-generation biologics; only guselkumab (IL-23i) was included in one study. The other 10 studies showed data on regaining response after failure of DR, safety, cost-effectiveness, and uptake and implementation, as well as information about IL-17/23i. The eligibility criteria to start DR included both absolute and relative Psoriasis Area and Severity Index (PASI) scores (PASI ≤3/≤5/PASI 75-100) and/or Dermatology Life Quality Index (DLQI) ≤3/≤5, or BSA ≤1/≤2, or Physician Global Assessment (PGA) ≤1/0-2 during a period ranging from 12 weeks to ≥1 year. Most studies used PASI ≤5 and/or DLQI ≤5 or PGA ≤1 for ≥6 months. DR strategies were mostly performed by stepwise interval prolongation in two steps (to 67% of the standard dose, followed by 50%). Some studies of IL-17/23i reduced the dose to ±25%. The tested DR strategies on stepwise or fixed DR on TNF-αi and IL-12/23i (three studies), as well as one \"on-demand\" dosing study on IL-23i guselkumab, were successful. In the case of relapse of DR on TNF-αi and IL-12/23i, clinical effectiveness was regained by retreatment with the standard dose. All studies showed substantial cost savings with the biologic DR of TNF-αi and IL-12/23i. The identified barriers against the implementation of DR were mainly a lack of guidelines and scientific evidence on effectiveness and safety, and a lack of time and (technical) support. The identified facilitators were mainly clear guidelines, feasible protocols, adequate education of patients and physicians, and cost reduction. In conclusion, DR seems promising, but a research gap still exists in randomized, prospective studies testing DR strategies, especially of IL-17/23i, hampering the completion of guidelines on DR. Taking into account the identified barriers and facilitators most likely results in a more successful implementation of biologic DR in practice.
摘要：
在先前的范围审查中已经描述了用于斑块状银屑病的第一代生物制剂（TNF-α抑制剂（i）和白介素（IL）-12/23i）的剂量减少（DR）。关于最新一代生物制剂（IL-17/23i）的DR的文献很少。当前的评论提供了有关所有生物制剂DR的先前范围审查的文献更新，包括最新一代，注重DR在实践中的吸收和实施。当前有关DR的文献检索显示，除了先前的综述外，还有14篇新文章。新发现的四篇文章测试了DR策略，主要集中在第一代生物制剂;只有guselkumab(IL-23i)被纳入一项研究.其他10项研究显示了DR失败后恢复反应的数据，安全,成本效益，以及吸收和实施，以及有关IL-17/23i的信息。开始DR的资格标准包括绝对和相对银屑病面积和严重程度指数（PASI）评分（PASI≤3/≤5/PASI75-100）和/或皮肤病生活质量指数（DLQI）≤3/≤5，或BSA≤1/≤2，或医师全球评估（PGA）≤1/0-2，时间从12周到≥1年。大多数研究使用PASI≤5和/或DLQI≤5或PGA≤1≥6个月。DR策略主要通过分两步逐步延长间隔（达到标准剂量的67％，其次是50%)。IL-17/23i的一些研究将剂量降低至±25%。对TNF-αi和IL-12/23i的逐步或固定DR的测试DR策略（三项研究），以及一项关于IL-23iguselkumab的“按需”给药研究，是成功的。在TNF-αi和IL-12/23i的DR复发的情况下，标准剂量再治疗可恢复临床疗效.所有研究均显示TNF-αi和IL-12/23i的生物学DR可节省大量成本。发现的阻碍实施DR的障碍主要是缺乏关于有效性和安全性的指南和科学证据，缺乏时间和（技术）支持。确定的主持人主要是明确的指导方针，可行的协议，对患者和医生进行充分的教育，和降低成本。总之,博士似乎很有希望，但是随机研究仍然存在差距，前瞻性研究测试DR策略，尤其是IL-17/23i，妨碍完成DR.考虑到已确定的障碍和促进因素，最有可能在实践中更成功地实施生物DR。
