Artikel
Adalimumab exposure and methotrexate effect in pediatric inflammatory rheumatic diseases
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Autoren
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Tatjana Welzel
- University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Rheumatology, Basel; University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Pharmacology and Pharmacometrics, Basel; University Children’s Hospital Basel (UKBB), University of Basel, Paediatric Reseach Centre, Basel; University Children’s Hospital Tuebingen, University of Tuebingen, Pediatric Rheumatology and autoinflammation reference center Tuebingen (arcT), Tuebingen
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Klervi Gohlen
- University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Pharmacology and Pharmacometrics, Basel
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Andrew Atkinson
- University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Pharmacology and Pharmacometrics, Basel; University Children’s Hospital Basel (UKBB), University of Basel, Paediatric Reseach Centre, Basel
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Verena Gotta
- University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Pharmacology and Pharmacometrics, Basel
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Jasmin B. Kümmerle-Deschner
- University Children’s Hospital Tuebingen, University of Tuebingen, Pediatric Rheumatology and autoinflammation reference center Tuebingen (arcT), Tuebingen
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Christine Michler
- University Children’s Hospital Tuebingen, University of Tuebingen, Pediatric Rheumatology and autoinflammation reference center Tuebingen (arcT), Tuebingen
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Gilbert Koch
- University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Pharmacology and Pharmacometrics, Basel
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Johannes N. Van den Anker
- University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Pharmacology and Pharmacometrics, Basel
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Marc Pfister
- University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Pharmacology and Pharmacometrics, Basel
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Andreas Wörner
- University Children’s Hospital Basel (UKBB), University of Basel, Pediatric Rheumatology, Basel
| Veröffentlicht: | 30. August 2023 |
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Gliederung
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Introduction: Adalimumab is commonly used in pediatric inflammatory rheumatic diseases (PiRD). Up to now, adalimumab is dosed in fixed weight-based bands, irrespective of co-medication/potential factors influencing adalimumab pharmacokinetics (PK). So far, no adalimumab target values are defined in PiRD. This pilot-study analyzed adalimumab concentrations in PiRD patients to better understand target values and adalimumab PK.
Methods: This is a two-center prospective trial in PiRD patients aged 2–18 years treated with adalimumab and methotrexate (group G1) or adalimumab alone (group G2) for ≥12 weeks. Adalimumab concentrations were collected at 1–9 (Cmax) and 10–14 days (Ctrough) post-dose during 3–6 months of adalimumab treatment. Furthermore, adalimumab concentrations were collected in PiRD patients 3–7 and 10–14 days after first adalimumab dose. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Analyses comparing Ctrough levels in G1 and G2 (t-test) and pharmacometric (PMX) pharmacokinetic analysis utilizing MONOLIX (V.2020 R1) for covariate investigation were performed.
Results: A total of 28 patients (N=14 each group) with a median age of 11.3 years (IQR 8.92–13.2), 15 (54%) females were included. Of these, 20 (71%) had juvenile idiopathic arthritis, 7 (25%) non-infectious uveitis and 1 (4%) chronic recurrent multifocal osteomyelitis. Median adalimumab Ctrough was similar in G1 (10.6 mg/L [IQR 8.9, 20.3]) to that in G2 (11.1 mg/L [IQR 6.6, 15.3], p=0.2) with high variability (range: 0.5 to 26 mg/L). In the PMX analysis, all 72 adalimumab concentrations were included. Although methotrexate was associated with a slight but non-significant decrease (15%) in adalimumab apparent clearance (CL/F) (p=0.5), longer treatment duration was associated with significantly increased CL/F (p=0.0005).
Conclusion: Given available data, no clinically meaningful effect of methotrexate co-medication on adalimumab exposure could be detected. However, high inter-individual variability and increasing adalimumab clearance over time is shown, highlighting importance of personalized dosing with model-based simulations.
T. Welzel and K. Gohlen contributed equally. M. Pfister and A. Woerner contributed equally.
Disclosure: None of the authors has a conflict of interest regarding abstract content.
