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<p>Non-systemic juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children and adolescents, and requires early and targeted treatment. In line with the treat-to-target concept, treatment is intensified if the defined therapeutic target is not reached – for example by increasing the dose, shortening the dosing interval or switching to another active substance. The clinical decision-making process is influenced by pharmacological aspects as well as patient-specific factors. This article highlights pharmacological considerations in treatment intensification using methotrexate (MTX) and adalimumab (ADM) as examples, two key agents in the treatment of non-systemic JIA. The high inter-individual variability in the pharmacokinetics and pharmacodynamics of MTX and ADM calls standardised dosing regimens into question and suggests the usefulness of individualised therapeutic approaches. Therapeutic drug monitoring (TDM) offers a promising tool for determining individual drug exposure and adjusting therapy accordingly. However, there is currently no routine recommendation for TDM of MTX or ADM. For MTX, the effective use of TDM requires a better understanding of relevant drug concentrations—in particular, intracellular MTX polyglutamates—as well as standardised and clinically established measurement methods. In the case of ADM, concentration measurements and standardized determination of anti-drug antibodies may be considered in individual cases to support treatment decisions and/or personalized dose adjustment. In order to establish TDM as a routine tool in paediatric rheumatology, further studies are required to define pediatric disease-specific reference and target ranges and to derive specific individualized dosing strategies.</p>

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Therapieintensivierung in der Rheumatologie am Beispiel der nicht-systemischen juvenilen idiopathischen Arthritis: die Sicht der Pharmakologie

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月29日

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  • Dominic Stefan Bräm,
  • Verena Gotta,
  • Tatjana Welzel

摘要

Non-systemic juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children and adolescents, and requires early and targeted treatment. In line with the treat-to-target concept, treatment is intensified if the defined therapeutic target is not reached – for example by increasing the dose, shortening the dosing interval or switching to another active substance. The clinical decision-making process is influenced by pharmacological aspects as well as patient-specific factors. This article highlights pharmacological considerations in treatment intensification using methotrexate (MTX) and adalimumab (ADM) as examples, two key agents in the treatment of non-systemic JIA. The high inter-individual variability in the pharmacokinetics and pharmacodynamics of MTX and ADM calls standardised dosing regimens into question and suggests the usefulness of individualised therapeutic approaches. Therapeutic drug monitoring (TDM) offers a promising tool for determining individual drug exposure and adjusting therapy accordingly. However, there is currently no routine recommendation for TDM of MTX or ADM. For MTX, the effective use of TDM requires a better understanding of relevant drug concentrations—in particular, intracellular MTX polyglutamates—as well as standardised and clinically established measurement methods. In the case of ADM, concentration measurements and standardized determination of anti-drug antibodies may be considered in individual cases to support treatment decisions and/or personalized dose adjustment. In order to establish TDM as a routine tool in paediatric rheumatology, further studies are required to define pediatric disease-specific reference and target ranges and to derive specific individualized dosing strategies.