title: Population Pharmacokinetics and Immunogenicity of Adalimumab in Adult Patients with Moderate-to-Severe Hidradenitis Suppurativa.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: AbbVie Inc., Clinical Pharmacology and Pharmacometrics, Department R4PK, Building AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA. ahmed.nader@abbvie.com.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Nader
authors.affiliation: AbbVie Deutschland GmbH & Co KG, Clinical Pharmacology and Pharmacometrics, Ludwigshafen am Rhein, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Beck
authors.affiliation: AbbVie Deutschland GmbH & Co KG, Clinical Pharmacology and Pharmacometrics, Ludwigshafen am Rhein, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Noertersheuser
authors.affiliation: AbbVie Inc., Pharmaceutical Research and Development, North Chicago, IL, USA.
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.affiliation: AbbVie Inc., Clinical Pharmacology and Pharmacometrics, Department R4PK, Building AP31-3, 1 North Waukegan Road, North Chicago, IL, 60064, USA.
authors.forename: Nael
authors.initials: N
authors.lastname: Mostafa
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D017497:Hidradenitis Suppurativa / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D055261:Immunogenetic Phenomena / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000068879:Adalimumab
keywords: Adalimumab; Baseline Body Weight; Hidradenitis Suppurativa; Maximum Response Rate; Visual Predictive Check