Towards therapeutic drug monitoring of TNF inhibitors for children with juvenile idiopathic arthritis: a scoping review

Abstract

ObjectivesBefore a clinician decides whether treatment with TNF inhibition in children with JIA has failed, one should ensure adequate systemic exposure has been achieved. Therapeutic drug monitoring might allow for improved treatment outcome with lower treatment-associated costs. However, this requires understanding of the pharmacokinetic (PK) characteristics, and the pharmacokinetic/pharmacodynamic (PK/PD) relationship for children with JIA. We performed a scoping review to summarize the available literature and identify areas for future research.MethodsA systematic search was conducted of the Medline, EMBASE, Web of Science and Cochrane databases as well as the clinicaltrials.gov registry. In total, 3959 records were screened and 130 publications were selected for full text assessment.ResultsTwenty publications were included and divided into three categories: PK (n = 9), PK/PD (n = 3) and anti-drug antibodies (n = 13). Industry involvement was significant in 14 publications. Although data are limited, systemic exposure to TNF inhibitors is generally lower in younger children but meta-analysis is not possible. The PK/PD relationship has had limited study but there is partial evidence for infliximab. Anti-drug antibodies are common, and are related to impaired clinical outcome with adalimumab and infliximab therapy.ConclusionThe current knowledge about the PK and PK/PD of TNF inhibitors in the treatment of children with JIA is limited, which prevents the introduction of TDM. Re-analysis of available data from previous trials, incorporation of pharmacologic assessments into existing biorepository studies as well as new prospective PK and PK/PD trials are required to obtain this knowledge.

Biomarkers of Response to Biologic Therapy in Juvenile Idiopathic Arthritis

“…However, the relation between ADA and treatment failure or adverse effects, the persistent or transient nature of ADA, as well as their prevalence in relation to treatment duration, vary across the different biologics (Doeleman et al, 2019). For instance, antibodies against etanercept, abatacept and canakinumab are non-neutralizing and are not linked with loss of efficacy (Mori et al, 2012;Sun et al, 2016;Doeleman et al, 2019;Verstegen et al, 2020). Similarly, despite the increased prevalence of ADA in patients treated with anakinra (82% at 12 months), the majority of patients develop non-neutralizing antibodies and do not lose treatment response (Lovell et al, 2000;Ilowite et al, 2009).…”

Дислипидемия Как Коморбидное Состояние У Детей С Ювенильным Идиопатическим Артритом

“…При обстеженні через рік у цих дітей відбувалося ще більше підвищення рівня ТГ (р < 0,05) та підвищення рівня ХС ЛПДНЩ (р < 0,05). Тобто, незважаючи на те, що [26,27]. Тому була виділена підгрупа дітей, які отримували комбіновану базисну терапію МТХ з імунобіологічним препаратом (ІБП) (блокатором ФНО-α) -8 осіб.…”

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“…Лікування інгібіторами фактора некрозу пухлини альфа (ФНП-α) сприяє зменшенню рівня автоімунного запалення. Також воно дозволяє домогтися значного поліпшення ендотеліальної функції [17][18][19]. Тому нами була проаналізована група дітей, які знаходились на комбінованій терапії метотрексатом та блокатором ФНП-α адалімумабом, що свідчить про наявність у цих хворих більш агресивної форми захворювання (табл.…”