Pediatric Rheumatology and autoinflammation reference center Tuebingen (arcT), Department of Pediatrics, Member of the European Reference Network for rare or low prevalence complex diseases, network Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA), University Children`s Hospital Tuebingen, Tuebingen, Germany.
Pediatric Pharmacology and Pharmacometrics, Pediatric Rheumatology, University Children`s Hospital Basel (UKBB), University of Basel, Spitalstrasse 33, CH, 4031, Basel, Switzerland.
Pediatr Rheumatol Online J. 2022 Aug 13;20(1):67. doi: 10.1186/s12969-022-00725-3.
Biological treatment and treat-to-target approaches guide the achievement of inactive disease and clinical remission in Autoinflammatory Diseases (AID). However, there is limited evidence addressing optimal tapering strategies and/or discontinuation of biological treatment in AID. This study evaluates available evidence of tapering biological treatment and explores key factors for successful tapering.
A systematic literature search was conducted in Embase, MEDLINE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials using the OVID platform (1990-08/2020). Bibliographic search of relevant reviews was also performed. Studies/case series (n ≥ 5) in AID patients aged ≤ 18 years with biological treatment providing information on tapering/treatment discontinuation were included. After quality assessment aggregated data were extracted and synthesized. Tapering strategies were explored.
A total of 6035 records were identified. Four papers were deemed high quality, all focused on systemic juvenile idiopathic arthritis (sJIA) (1 open-label randomized trial, 2 prospective, 1 retrospective observational study). Biological treatment included anakinra (n = 2), canakinumab (n = 1) and tocilizumab (n = 1). Strategies in anakinra tapering included alternate-day regimen. Canakinumab tapering was performed randomized for dose reduction or interval prolongation, whereas tocilizumab was tapered by interval prolongation. Key factors identified included early start of biological treatment and sustained inactive disease.
Tapering of biological treatment after sustained inactive disease should be considered. Guidance for optimal strategies is limited. Future studies may leverage therapeutic drug monitoring in combination with pharmacometric modelling to further enhance personalized "taper-to-target" strategies respecting individual patients and diseases aspects.
生物治疗和靶向治疗方法指导自身炎症性疾病（AID）达到无活动疾病和临床缓解。然而，关于 AID 中生物治疗的最佳减量策略和/或停药，证据有限。本研究评估了减量生物治疗的现有证据，并探讨了成功减量的关键因素。
使用 OVID 平台在 Embase、MEDLINE、Cochrane 系统评价数据库和 Cochrane 对照试验中心注册库中进行了系统文献检索（1990-08/2020）。还对相关综述的参考文献进行了检索。纳入了在年龄≤18 岁的 AID 患者中进行的生物治疗提供减量/治疗停止信息的研究/病例系列（n≥5）。经质量评估后，提取并综合了汇总数据。探索了减量策略。
共确定了 6035 条记录。4 篇论文被认为是高质量的，均聚焦于全身型幼年特发性关节炎（sJIA）（1 项开放性随机试验、2 项前瞻性研究、1 项回顾性观察研究）。生物治疗包括阿那白滞素（n=2）、卡那单抗（n=1）和托珠单抗（n=1）。阿那白滞素减量策略包括隔日方案。卡那单抗减量采用随机减量或延长间隔，托珠单抗通过延长间隔减量。确定的关键因素包括早期开始生物治疗和持续无活动疾病。
应考虑在持续无活动疾病后进行生物治疗减量。最佳策略的指导有限。未来的研究可以利用治疗药物监测与药效学建模相结合，进一步增强个性化的“靶向治疗”策略，同时尊重患者和疾病的个体特征。
