Health, Medical and Neuropsychology unit, Leiden University, Leiden, P.O. Box 9500, The Netherlands.
Leiden Institute for Brain and Cognition, Leiden, P.O. Box 9600, The Netherlands.
Pediatr Rheumatol Online J. 2020 Feb 7;18(1):12. doi: 10.1186/s12969-020-0407-5.
Methotrexate (MTX) therapy has proven to be a successful and safe treatment for Juvenile Idiopathic Arthritis (JIA). Despite the high efficacy rates of MTX, treatment outcomes are often complicated by burdensome gastro-intestinal side effects. Intolerance rates for MTX in children are high (approximately 50%) and thus far no conclusive effective treatment strategies to control for side effects have been found. To address this need, this article proposes an innovative research approach based on pharmacological conditioning, to reduce MTX intolerance.
A collaboration between medical psychologists, pediatric rheumatologists, pharmacologists and patient groups was set up to develop an innovative research design that may be implemented to study potential improved control of side effects in JIA, by making use of the psychobiological principles of pharmacological conditioning. In pharmacological conditioning designs, learned positive associations from drug therapies (conditioning effects) are integrated in regular treatment regimens to maximize treatment outcomes. Medication regimens with immunosuppressant drugs that made use of pharmacological conditioning principles have been shown to lead to optimized therapeutic effects with reduced drug dosing, which might ultimately cause a reduction in side effects.
This research design is tailored to serve the needs of the JIA patient group. We developed a research design in collaboration with an interdisciplinary research group consisting of patient representatives, pediatric rheumatologists, pharmacologists, and medical psychologists.
Based on previous experimental and clinical findings of pharmacological conditioning with immune responses, we propose that the JIA patient group is particularly suited to benefit from a pharmacological conditioning design. Moreover, findings from this study may potentially also be promising for other patient groups that endure long-lasting drug therapies.
甲氨蝶呤（MTX）治疗已被证明是治疗幼年特发性关节炎（JIA）的一种成功且安全的治疗方法。尽管 MTX 的疗效很高，但治疗结果常常因胃肠道副作用而变得复杂。儿童对 MTX 的不耐受率很高（约 50%），迄今为止，尚未找到有效的治疗策略来控制副作用。为了解决这一需求，本文提出了一种基于药物调节的创新研究方法，以降低 MTX 的不耐受性。
成立了一个由医学心理学家、儿科风湿病学家、药理学家和患者团体组成的合作团队，以开发一种创新的研究设计，该设计可以通过利用药物调节的心理生物学原理来研究潜在的改善 JIA 副作用控制的方法。在药物调节设计中，药物治疗的习得性正性联想（调节作用）被整合到常规治疗方案中，以最大限度地提高治疗效果。已证明利用药物调节原理的免疫抑制剂药物治疗方案可导致优化的治疗效果和减少药物剂量，最终可能减少副作用。
该研究设计是为满足 JIA 患者群体的需求而定制的。我们与一个由患者代表、儿科风湿病学家、药理学家和医学心理学家组成的跨学科研究团队合作，开发了一种研究设计。
基于药物调节与免疫反应的实验和临床发现，我们提出 JIA 患者群体特别适合从药物调节设计中受益。此外，这项研究的结果也可能对其他需要长期药物治疗的患者群体有潜在的希望。
