Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial

Objectives The objectives of this study are to identify a therapeutic serum level for adalimumab associated with remission and low disease activity in patients with rheumatoid arthritis.Methods Associations between serum adalimumab trough levels and disease activity were examined using longitudinal...

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Main Authors: Joseph Sexton, Daniel Aletaha, Eirik Klami Kristianslund, Espen Andre Haavardsholm, Nils Bolstad, Johanna Elin Gehin, Silje Watterdal Syversen, David John Warren, Guro Løvik Goll, Ingrid Jyssum, Rolf Anton Klaasen
Format: Article
Language:English
Published: BMJ Publishing Group 2024-11-01
Series:RMD Open
Online Access:https://rmdopen.bmj.com/content/10/4/e004888.full
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author Joseph Sexton
Daniel Aletaha
Eirik Klami Kristianslund
Espen Andre Haavardsholm
Nils Bolstad
Johanna Elin Gehin
Silje Watterdal Syversen
David John Warren
Guro Løvik Goll
Ingrid Jyssum
Rolf Anton Klaasen
author_facet Joseph Sexton
Daniel Aletaha
Eirik Klami Kristianslund
Espen Andre Haavardsholm
Nils Bolstad
Johanna Elin Gehin
Silje Watterdal Syversen
David John Warren
Guro Løvik Goll
Ingrid Jyssum
Rolf Anton Klaasen
author_sort Joseph Sexton
collection DOAJ
description Objectives The objectives of this study are to identify a therapeutic serum level for adalimumab associated with remission and low disease activity in patients with rheumatoid arthritis.Methods Associations between serum adalimumab trough levels and disease activity were examined using longitudinal data from a 48-week randomised phase III trial including patients with tumour necrosis factor inhibitor-naïve rheumatoid arthritis with active disease starting adalimumab treatment. Disease activity was classified according to 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate and C reactive protein (CRP) levels.Results Adalimumab trough levels were recorded longitudinally for 336, 330 and 302 patients at weeks 12, 24 and 48, respectively. All patients received concomitant methotrexate. Median adalimumab trough levels were 6.4 mg/L (IQR 3.4–9.5) at week 12, 7.5 mg/L (IQR 3.5–10.9) at week 24 and 7.6 mg/L (IQR 3.6–12.0) at week 48. In serial serum samples from weeks 12, 24 and 48, trough levels ≥3.9 mg/L were associated with DAS28 remission (OR 3.88 (95% CI 1.80, 8.38), p<0.001) and lower CRP levels (p<0.001). Week 12 trough levels ≥3.5 mg/L were associated with DAS28 low disease activity at week 24 (OR 2.62 (1.50, 4.56), p<0.001) and remission at week 48 (OR 1.99 (1.02, 3.88), p=0.04), as well as lower CRP levels at both time points (p<0.001).Conclusion Adalimumab trough levels above 4.0 mg/L were associated with remission/low disease activity throughout the first year of adalimumab therapy and can be considered a lower target level for therapeutic drug monitoring of adalimumab therapy.
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spelling doaj-art-f7d775b33b4a44a5b570036de94387882024-11-14T05:50:07ZengBMJ Publishing GroupRMD Open2056-59332024-11-0110410.1136/rmdopen-2024-004888Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trialJoseph Sexton0Daniel Aletaha1Eirik Klami Kristianslund2Espen Andre Haavardsholm3Nils Bolstad4Johanna Elin Gehin5Silje Watterdal Syversen6David John Warren7Guro Løvik Goll8Ingrid Jyssum9Rolf Anton Klaasen10Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayDivision of Rheumatology, Medical University of Vienna, Vienna, AustriaCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayDepartment of Medical Biochemistry, Oslo University Hospital, Oslo, NorwayDepartment of Medical Biochemistry, Oslo University Hospital, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayDepartment of Medical Biochemistry, Oslo University Hospital, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayCenter for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, NorwayDepartment of Medical Biochemistry, Oslo University Hospital, Oslo, NorwayObjectives The objectives of this study are to identify a therapeutic serum level for adalimumab associated with remission and low disease activity in patients with rheumatoid arthritis.Methods Associations between serum adalimumab trough levels and disease activity were examined using longitudinal data from a 48-week randomised phase III trial including patients with tumour necrosis factor inhibitor-naïve rheumatoid arthritis with active disease starting adalimumab treatment. Disease activity was classified according to 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate and C reactive protein (CRP) levels.Results Adalimumab trough levels were recorded longitudinally for 336, 330 and 302 patients at weeks 12, 24 and 48, respectively. All patients received concomitant methotrexate. Median adalimumab trough levels were 6.4 mg/L (IQR 3.4–9.5) at week 12, 7.5 mg/L (IQR 3.5–10.9) at week 24 and 7.6 mg/L (IQR 3.6–12.0) at week 48. In serial serum samples from weeks 12, 24 and 48, trough levels ≥3.9 mg/L were associated with DAS28 remission (OR 3.88 (95% CI 1.80, 8.38), p<0.001) and lower CRP levels (p<0.001). Week 12 trough levels ≥3.5 mg/L were associated with DAS28 low disease activity at week 24 (OR 2.62 (1.50, 4.56), p<0.001) and remission at week 48 (OR 1.99 (1.02, 3.88), p=0.04), as well as lower CRP levels at both time points (p<0.001).Conclusion Adalimumab trough levels above 4.0 mg/L were associated with remission/low disease activity throughout the first year of adalimumab therapy and can be considered a lower target level for therapeutic drug monitoring of adalimumab therapy.https://rmdopen.bmj.com/content/10/4/e004888.full
spellingShingle Joseph Sexton
Daniel Aletaha
Eirik Klami Kristianslund
Espen Andre Haavardsholm
Nils Bolstad
Johanna Elin Gehin
Silje Watterdal Syversen
David John Warren
Guro Løvik Goll
Ingrid Jyssum
Rolf Anton Klaasen
Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial
RMD Open
title Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial
title_full Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial
title_fullStr Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial
title_full_unstemmed Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial
title_short Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial
title_sort therapeutic serum level for adalimumab in rheumatoid arthritis explorative analyses of data from a randomised phase iii trial
url https://rmdopen.bmj.com/content/10/4/e004888.full
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