Prospective study to characterize adalimumab exposure in pediatric patients with rheumatic diseases
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 ($ G_{A-M} $) or adalimumab alone ($ G_{A} $) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1–9 (maximum concentration; $ C_{max} $), and 10–14 days (minimum concentration; $ C_{min} $) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized $ C_{min} $ were compared between $ G_{A-M} $ and $ G_{A} $ 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. $ G_{A-M} $ included more females (71.4%; $ G_{A} $ 35.7%, p = 0.13). At first study visit, children in $ G_{A-M} $ had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to $ G_{A} $ (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 $ G_{A-M} $ had a 27% higher median overall exposure compared to $ G_{A} $, although median $ C_{min} $ adalimumab values were statistically not different (p = 0.3). $ C_{min} $ values ≥ 8 mg/L (upper limit RA) were more frequently observed in $ G_{A-M} $ versus $ G_{A} $ (79% versus 64%). Overall, a wide range of $ C_{min} $ 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 - 22(2024), 1 vom: 02. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Welzel, Tatjana [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
BDMARDs |
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| Anmerkungen: |
© The Author(s) 2023 |
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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): |
SPR054232929 |
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| 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. Methods A two-center prospective study in PRD patients aged 2–18 years treated with adalimumab and methotrexate ($ G_{A-M} $) or adalimumab alone ($ G_{A} $) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1–9 (maximum concentration; $ C_{max} $), and 10–14 days (minimum concentration; $ C_{min} $) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized $ C_{min} $ were compared between $ G_{A-M} $ and $ G_{A} $ 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. $ G_{A-M} $ included more females (71.4%; $ G_{A} $ 35.7%, p = 0.13). At first study visit, children in $ G_{A-M} $ had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to $ G_{A} $ (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 $ G_{A-M} $ had a 27% higher median overall exposure compared to $ G_{A} $, although median $ C_{min} $ adalimumab values were statistically not different (p = 0.3). $ C_{min} $ values ≥ 8 mg/L (upper limit RA) were more frequently observed in $ G_{A-M} $ versus $ G_{A} $ (79% versus 64%). Overall, a wide range of $ C_{min} $ 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. | ||
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