title: Impact of immunogenicity on pharmacokinetics, efficacy and safety of adalimumab in adult patients with moderate to severe chronic plaque psoriasis.
abstract: BACKGROUND
  Adalimumab is a tumour necrosis factor-alpha antibody approved for treatment of moderate to severe chronic plaque psoriasis.
  
  
  OBJECTIVE
  To characterise population pharmacokinetics of adalimumab 40 mg every other week dosing regimen and impact of immunogenicity on pharmacokinetics, efficacy and safety in psoriasis patients.
  
  
  METHODS
  Patients were enrolled in a Phase 3 study comprising a 16-week double-blind, placebo-controlled period, a 17-week open-label period for Week 16 Psoriasis Area and Severity Index (PASI) 75 responders, and a 19-week double-blind, placebo-controlled period for Week 33 PASI 75 responders. Serum adalimumab and anti-adalimumab antibody (AAA) concentrations were measured and a population pharmacokinetic model devleoped to identify patient/disease factors affecting adalimumab pharmacokinetics. Impact of immunogenicity on treatment efficacy and safety was also assessed.
  
  
  RESULTS
  Week 33 mean adalimumab concentration was 5.2 μg/mL. Week 16 responders had higher adalimumab concentrations than non-responders (6.3 vs. 2.2 μg/mL). Bodyweight and study were significant covariates in population pharmacokinetic model with weight accounting for 19% and 29% of variability in adalimumab clearance and volume of distribution, respectively. A total of 8.8% of adalimumab-treated patients tested AAA positive and had twofold higher adalimumab clearance. PASI 75 response rate was comparable between AAA+ and AAA- patients at Weeks 33 and 52 (Week 33: 36% vs. 22.5%, Week 52: 21.1% vs. 17.8%) and adverse events incidence was similar between the two groups.
  
  
  CONCLUSIONS
  Patient weight and study significantly affect adalimumab clearance and volume of distribution in psoriasis patients. Development of AAAs result in lower adalimumab exposure and efficacy with no effect on adverse events incidence.
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Mostafa
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Nader
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: P
authors.initials: P
authors.lastname: Noertersheuser
authors.affiliation: Fort Healthcare, Fort Atkinson, WI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Okun
authors.affiliation: AbbVie Inc., North Chicago, IL, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Awni
mesh_terms: D000068879:Adalimumab / Q000097:blood / Q000276:immunology* / Q000494:pharmacology / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000276:immunology* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood; D001835:Body Weight; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000068879:Adalimumab