title: Anti-adalimumab antibodies in psoriasis: lack of clinical utility and laboratory evidence.
abstract: Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug's immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients.
  
  
  
  Case-control, longitudinal.
  
  
  
  Single centre.
  
  
  
  Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab.Healthy subjects: (group V; n=15) never treated with immunosuppressants or biologicals.
  
  
  
  All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months.
  
  
  
  Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISA-based measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα.
  
  
  
  The false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naïve to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-time-point positivity in group III during follow-up) accounted for 33% of the total. The prevalence of anti-drug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores.
  
  
  
  High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay's usefulness. Accurate clinical evaluation is key to early identification of treatment failures.
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italia.
authors.forename: G
authors.identifier: 0000-0002-8365-985X
authors.initials: G
authors.lastname: Lombardi
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italia.
authors.forename: S
authors.initials: S
authors.lastname: Perego
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italia.
authors.forename: V
authors.initials: V
authors.lastname: Sansoni
authors.affiliation: Department of Dermatology and Venereology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italia.
authors.forename: M
authors.initials: M
authors.lastname: Diani
authors.affiliation: Laboratory of Experimental Biochemistry and Molecular Biology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italia.|Vita-Salute San Raffaele University, Milano, Italia.
authors.forename: G
authors.initials: G
authors.lastname: Banfi
authors.affiliation: Department of Dermatology and Venereology, I.R.C.C.S. Istituto Ortopedico Galeazzi, Milano, Italia.|Department of Biomedical Sciences for Health, University of Milano, Milano, Italia.
authors.forename: G
authors.initials: G
authors.lastname: Altomare
mesh_terms: D000068879:Adalimumab / Q000276:immunology / Q000627:therapeutic use*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology; D012720:Severity of Illness Index; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab
keywords: ELISA; adalimumab; anti-drug antibodies