Prospective study to characterize adalimumab exposure in pediatric patients with rheumatic diseases
© 2023. The Author(s)..
BACKGROUND: In pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2-8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate.
METHODS: A two-center prospective study in PRD patients aged 2-18 years treated with adalimumab and methotrexate (GA-M) or adalimumab alone (GA) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1-9 (maximum concentration; Cmax), and 10-14 days (minimum concentration; Cmin) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized Cmin were compared between GA-M and GA using a standard t-test.
RESULTS: Twenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent multifocal osteomyelitis (3.6%) completed the study. GA-M included more females (71.4%; GA 35.7%, p = 0.13). At first study visit, children in GA-M had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to GA (15.8 months [IQR 8.5, 30.8], p = 0.8). Adalimumab dosing was similar between both groups (median dose 40 mg every 14 days) and observed DA was low. Children in GA-M had a 27% higher median overall exposure compared to GA, although median Cmin adalimumab values were statistically not different (p = 0.3). Cmin values ≥ 8 mg/L (upper limit RA) were more frequently observed in GA-M versus GA (79% versus 64%). Overall, a wide range of Cmin values was observed in PRD (0.5 to 26 mg/L).
CONCLUSION: This study revealed a high heterogeneity in adalimumab exposure in PRD. Adalimumab exposure tended to be higher with methotrexate co-treatment compared to adalimumab monotherapy although differences were not statistically significant. Most children showed adalimumab exposure exceeding those reported for RA with clinical response, particularly with methotrexate co-treatment. This highlights the need of further investigations to establish model-based personalized treatment strategies in PRD to avoid under- and overexposure.
TRIAL REGISTRATION: NCT04042792 , registered 02.08.2019.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
Pediatric rheumatology online journal - 22(2024), 1 vom: 02. Jan., Seite 5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Welzel, Tatjana [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.01.2024 Date Revised 06.01.2024 published: Electronic ClinicalTrials.gov: NCT04042792 Citation Status MEDLINE |
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| doi: |
10.1186/s12969-023-00930-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM36657650X |
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| 041 | |a eng | ||
| 100 | 1 | |a Welzel, Tatjana |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Prospective study to characterize adalimumab exposure in pediatric patients with rheumatic diseases |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Completed 05.01.2024 | ||
| 500 | |a Date Revised 06.01.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04042792 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a BACKGROUND: In pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2-8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate | ||
| 520 | |a METHODS: A two-center prospective study in PRD patients aged 2-18 years treated with adalimumab and methotrexate (GA-M) or adalimumab alone (GA) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1-9 (maximum concentration; Cmax), and 10-14 days (minimum concentration; Cmin) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized Cmin were compared between GA-M and GA using a standard t-test | ||
| 520 | |a RESULTS: Twenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent multifocal osteomyelitis (3.6%) completed the study. GA-M included more females (71.4%; GA 35.7%, p = 0.13). At first study visit, children in GA-M had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to GA (15.8 months [IQR 8.5, 30.8], p = 0.8). Adalimumab dosing was similar between both groups (median dose 40 mg every 14 days) and observed DA was low. Children in GA-M had a 27% higher median overall exposure compared to GA, although median Cmin adalimumab values were statistically not different (p = 0.3). Cmin values ≥ 8 mg/L (upper limit RA) were more frequently observed in GA-M versus GA (79% versus 64%). Overall, a wide range of Cmin values was observed in PRD (0.5 to 26 mg/L) | ||
| 520 | |a CONCLUSION: This study revealed a high heterogeneity in adalimumab exposure in PRD. Adalimumab exposure tended to be higher with methotrexate co-treatment compared to adalimumab monotherapy although differences were not statistically significant. Most children showed adalimumab exposure exceeding those reported for RA with clinical response, particularly with methotrexate co-treatment. This highlights the need of further investigations to establish model-based personalized treatment strategies in PRD to avoid under- and overexposure | ||
| 520 | |a TRIAL REGISTRATION: NCT04042792 , registered 02.08.2019 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Drug exposure | |
| 650 | 4 | |a Heterogeneity | |
| 650 | 4 | |a Pharmacodynamics | |
| 650 | 4 | |a Pharmacokinetics | |
| 650 | 4 | |a Target concentration | |
| 650 | 4 | |a Therapeutic drug monitoring | |
| 650 | 4 | |a bDMARDs | |
| 650 | 7 | |a Adalimumab |2 NLM | |
| 650 | 7 | |a FYS6T7F842 |2 NLM | |
| 650 | 7 | |a Methotrexate |2 NLM | |
| 650 | 7 | |a YL5FZ2Y5U1 |2 NLM | |
| 650 | 7 | |a Antirheumatic Agents |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal, Humanized |2 NLM | |
| 700 | 1 | |a Golhen, Klervi |e verfasserin |4 aut | |
| 700 | 1 | |a Atkinson, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Gotta, Verena |e verfasserin |4 aut | |
| 700 | 1 | |a Ternant, David |e verfasserin |4 aut | |
| 700 | 1 | |a Kuemmerle-Deschner, Jasmin B |e verfasserin |4 aut | |
| 700 | 1 | |a Michler, Christine |e verfasserin |4 aut | |
| 700 | 1 | |a Koch, Gilbert |e verfasserin |4 aut | |
| 700 | 1 | |a van den Anker, Johannes N |e verfasserin |4 aut | |
| 700 | 1 | |a Pfister, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Woerner, Andreas |e verfasserin |4 aut | |
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