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Population Pharmacokinetics and Immunogenicity of Adalimumab in Adult Patients with Moderate-to-Severe Hidradenitis Suppurativa

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Abstract

Introduction

Hidradenitis suppurativa (HS) is a serious, debilitating, chronic inflammatory skin disease. Adalimumab is a fully human, immunoglobulin G1 monoclonal antibody specific for tumor necrosis factor-alpha recently approved for use in patients with HS. The aim of this study is to describe the population pharmacokinetics and immunogenicity of adalimumab in adult patients with HS.

Methods

Data from one phase II and two phase III studies were included in the analysis. Serial serum adalimumab concentrations and anti-adalimumab antibody (AAA) development status were used to develop the population pharmacokinetic model. The population pharmacokinetic analysis involved evaluating the effects of potential covariates on adalimumab pharmacokinetics.

Results

Mean serum adalimumab concentrations after 40-mg weekly dosing reached steady state (10–12 µg/mL in the phase II study and 7 µg/mL in the phase III studies) by week 2 and were maintained through week 12. The percentage of patients testing positive for AAA was low (10% in the phase II study and 7% in the phase III studies). Adalimumab pharmacokinetics was described by a one-compartment model with first-order absorption. Significant covariates for clearance included the presence of AAA, baseline C-reactive protein, and baseline body weight.

Conclusions

Adalimumab pharmacokinetics in HS patients was described using a one-compartment model with weight, baseline C-reactive protein, and AAA affecting adalimumab exposure. AAA development results in decreased adalimumab concentrations with a potential decrease in efficacy. Serum adalimumab concentrations in HS patients receiving 40-mg weekly dosing were similar to those observed in other indications under approved dosing regimens.

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Acknowledgements

The authors thank the clinical sites and investigators and AbbVie Inc. study team members for assistance with the conduct of the study.

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Authors and Affiliations

  1. AbbVie Inc., Clinical Pharmacology and Pharmacometrics, Department R4PK, Building AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA

    Ahmed Nader & Nael Mostafa

  2. AbbVie Deutschland GmbH & Co KG, Clinical Pharmacology and Pharmacometrics, Ludwigshafen am Rhein, Germany

    Denise Beck & Peter Noertersheuser

  3. AbbVie Inc., Pharmaceutical Research and Development, North Chicago, IL, USA

    David Williams

Authors
  1. Ahmed Nader
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  2. Denise Beck
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  3. Peter Noertersheuser
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  4. David Williams
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  5. Nael Mostafa
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Corresponding author

Correspondence to Ahmed Nader.

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Funding

The study was sponsored by AbbVie Inc. AbbVie Inc. contributed to the study design, research, and interpretation of data, and the writing, reviewing, and approving of the publication. Medical writing support was provided by Amy Rohrlack, a medical writer employed by AbbVie Inc.

Conflict of interest

All authors are employees of AbbVie Inc. and may hold AbbVie Inc. stock or stock options.

Ethics approval and consent to participate

The trials were conducted in accordance with the ethical principles set forth in the Declaration of Helsinki and its amendments, International Conference for Harmonisation–Good Clinical Practice guidelines, and local guidelines and regulations. The protocols and informed consent forms were approved by the institutional review boards/ethics committees. All patients provided written informed consent before participating in study activities.

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Nader, A., Beck, D., Noertersheuser, P. et al. Population Pharmacokinetics and Immunogenicity of Adalimumab in Adult Patients with Moderate-to-Severe Hidradenitis Suppurativa. Clin Pharmacokinet 56, 1091–1102 (2017). https://doi.org/10.1007/s40262-016-0502-4

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