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Early At-Home Measurement of Adalimumab Concentrations to Guide Anti-TNF Precision Dosing: A Pilot Study

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Abstract

Background and Objective

Underdosing of adalimumab can result in non-response and poor disease control in patients with rheumatic disease or inflammatory bowel disease. In this pilot study we aimed to predict adalimumab concentrations with population pharmacokinetic model-based Bayesian forecasting early in therapy.

Methods

Adalimumab pharmacokinetic models were identified with a literature search. A fit-for-purpose evaluation of the model was performed for rheumatologic and inflammatory bowel disease (IBD) patients with adalimumab peak (first dose) and trough samples (first and seventh dose) obtained by a volumetric absorptive microsampling technique. Steady state adalimumab concentrations were predicted after the first adalimumab administration. Predictive performance was calculated with mean prediction error (MPE) and normalised root mean square error (RMSE).

Results

Thirty-six patients (22 rheumatologic and 14 IBD) were analysed in our study. After stratification for absence of anti-adalimumab antibodies, the calculated MPE was −2.6% and normalised RMSE 24.0%. Concordance between predicted and measured adalimumab serum concentrations falling within or outside the therapeutic window was 75%. Three patients (8.3%) developed detectable concentrations of anti-adalimumab antibodies.

Conclusion

This prospective study demonstrates that adalimumab concentrations at steady state can be predicted from early samples during the induction phase.

Clinical Trial Registration

The trial was registered in the Netherlands Trial Register with trial registry number NTR 7692 (www.trialregister.nl).

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Acknowledgements

We thank Wil Adriaans, Louise Merry-Meier and Antoinette Piepenbrock-van Schooten for their efforts for the inclusion of patients in this trial.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmacology, Máxima Medical Center, 5504 DB, Veldhoven, The Netherlands

    Paul A. G. de Klaver & Luc J. J. Derijks

  2. InsightRx Inc, San Francisco, USA

    Ron J. Keizer

  3. Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

    Rob ter Heine

  4. Department of Gastroenterology, Radboud University Medical Center, Nijmegen, The Netherlands

    Lisa Smits & Frank Hoentjen

  5. Department of Gastroenterology, Máxima Medical Center, Veldhoven, The Netherlands

    Paul J. Boekema

  6. Department of Rheumatology, Máxima Medical Center, Eindhoven, The Netherlands

    Inge Kuntzel

  7. Biologics Laboratory, Sanquin Diagnostic Services, Amsterdam, The Netherlands

    Tiny Schaap, Annick de Vries, Karien Bloem & Theo Rispens

  8. Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands

    Theo Rispens

  9. Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada

    Frank Hoentjen

  10. Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center, Maastricht, The Netherlands

    Luc J. J. Derijks

  11. Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

    Theo Rispens

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  1. Paul A. G. de Klaver
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Corresponding author

Correspondence to Paul A. G. de Klaver.

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Funding

No funding was received to conduct this study.

Author contributions

Conceptualization: P.K., R.K., R.H. and L.D., methodology: P.K., R.K., R.H. and L.D., software: R.H. and R.K., formal analysis: A.V., T.S., K.B. and T.R., investigation: P.K., P.B., I.K., F.H. and L.S., data curation: P.K., R.K. and R.H., writing—original draft preparation: P.K., writing—review and editing: R.K., R.H., F.H., P.B., I.K., T.S., A.V., K.B., T.R., L.S. and L.D., supervision: P.K. and L.D.

Conflict of Interest

F.H.: speaker for Abbvie, Janssen–Cilag, MSD, Takeda, Celltrion, Teva, Sandoz and Dr Falk. Funding (grants/honoraria): Dr Falk, Janssen–Cilag, Abbvie and Takeda. Consulting fees: Celgene. P.K., R.K., R.H., L.D., A.V., T.S., K.B., T.R., P.B., I.K. and L.S. declare that they have no conflicts of interest.

Ethics Approval

The study was approved by the local ethics committee. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Máxima Medisch Centrum (W18.147, 22-01-2019).

Patient Consent

Informed consent was obtained from all subjects involved in the study.

Consent for publication

Not applicable.

Data Availability

Raw data were generated at Máxima Medical Center and Radboud University Medical Center. Derived data supporting the findings of this study are available from the corresponding author (P.K.) on request.

Code Availability

Not applicable.

Supplementary Information

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Supplementary file 1 (PDF 530 KB)

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de Klaver, P.A.G., Keizer, R.J., ter Heine, R. et al. Early At-Home Measurement of Adalimumab Concentrations to Guide Anti-TNF Precision Dosing: A Pilot Study. Eur J Drug Metab Pharmacokinet 48, 377–385 (2023). https://doi.org/10.1007/s13318-023-00835-7

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