title: The Association between Clinical Response to Ustekinumab and Immunogenicity to Ustekinumab and Prior Adalimumab.
abstract: BACKGROUND
  Immunogenicity due to antidrug antibodies (ADA) to tumor necrosis factor (TNF)-α antagonists is known to decrease treatment response. However, few studies have investigated ADA in ustekinumab, an interleukin-12 and -23 antagonist, in a clinical setting. This study aimed to investigate the immunogenicity of ustekinumab and its clinical consequences in psoriasis.
  
  
  METHODS
  This prospective observational study enrolled 76 patients with plaque psoriasis who were treated with ustekinumab for a minimum of 7 months. Blood samples were drawn just prior to scheduled ustekinumab injection during clinic visits. Levels of anti-ustekinumab antibody (AUA) and serum ustekinumab concentration were measured respectively by radioimmunoassays and enzyme-linked immunoassays respectively, and correlated to clinical data and Psoriasis Area and Severity Index (PASI).
  
  
  RESULTS
  AUA was detected in 6.5% of patients after a mean of 13 months of treatment. Patients with positive AUA had significantly lower serum ustekinumab concentrations (0.01 vs. 0.2 mg/L, p<0.001) and lower PASI 50 response than patients without AUA (0% vs. 69%, p = 0.004).The percentage of AUA formation was comparable between patients who had failed previous adalimumab with or without anti-adalimumab antibodies (AAA) (14.3% vs. 12.5%, p = 1.00). However, a higher proportion of switchers without AAA obtaining PASI50 (71.4% vs. 37.5%) and PASI75 response (42.9% vs.12.5%) within 7 months of ustekinumab treatment than with AAA though this difference did not reach statistical significance.
  
  
  CONCLUSIONS
  Our results suggest that presence of AUA was significantly associated with treatment failure for ustekinumab, though limited by a small sample size. Also, determining the presence of ADA to antecedent TNF-α antagonists may assist in choosing an optimized subsequent treatment modality achieving treatment success.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan.|Department of Dermatology, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan.|Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hsien-Yi
authors.initials: HY
authors.lastname: Chiu
authors.affiliation: Department of Dermatology, Far Eastern Memorial Hospital, New Taipei, Taiwan.
authors.forename: Thomas Waitao
authors.initials: TW
authors.lastname: Chu
authors.affiliation: Department of Dermatology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Yu-Pin
authors.initials: YP
authors.lastname: Cheng
authors.affiliation: Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Tsen-Fang
authors.initials: TF
authors.lastname: Tsai
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D000906:Antibodies / Q000097:blood; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D018664:Interleukin-12 / Q000737:chemistry; D053759:Interleukin-23 / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology*; D011863:Radioimmunoassay; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000069549:Ustekinumab / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D003879:Dermatologic Agents; D053759:Interleukin-23; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000069549:Ustekinumab; D000068879:Adalimumab