title: Role of the HLA-C*06 allele in clinical response to ustekinumab: evidence from real life in a large cohort of European patients.
abstract: BACKGROUND
  Little is known about the role of the HLA-C*06 allele in the response to psoriasis treatments.
  
  
  OBJECTIVE
  To confirm the role of HLA-C*06 as a pharmacogenetic marker of response to ustekinumab in a new, large cohort of patients involving four European centres.
  
  
  METHODS
  In this retrospective multicentre study we reviewed data of 255 patients with psoriasis genotyped for HLA-C*06 who started ustekinumab treatment between January 2014 and March 2015. The severity of psoriasis and response to treatment were evaluated using the Psoriasis Area and Severity Index (PASI) score at baseline and then at follow-up visits on weeks 4, 12, 28, 40 and 52. The primary end point was the proportion of patients achieving ≥ 50% reduction in PASI score (PASI 50) at week 4. A ≥ 75% reduction in PASI score (PASI 75) and a ≥ 90% reduction in the PASI score (PASI 90) after 12 weeks were secondary end points.
  
  
  RESULTS
  At week 4, PASI 50 was seen in 71·7% of HLA-C*06-positive (C*06POS) and 35·2% of HLA-C*06-negative (C*06NEG) patients. At week 12, PASI 75 was reached by 69.1% of C*06POS patients and 40·5% of C*06NEG patients. After 52 weeks, PASI 75 was reached by 83.7% of C*06POS patients and 58.8% of C*06NEG patients.
  
  
  CONCLUSIONS
  The results from our new, large cohort of European patients treated with ustekinumab in daily clinical practice confirm the role of HLA-C*06 as a potential predictor of response to ustekinumab.
authors.affiliation: Department of Dermatology, University of Rome Tor Vergata, Italy.
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-3070-4071
authors.initials: M
authors.lastname: Talamonti
authors.affiliation: Department of Dermatology, University of Rome Tor Vergata, Italy.
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-3424-5175
authors.initials: M
authors.lastname: Galluzzo
authors.affiliation: Department of Dermatology, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: van den Reek
authors.affiliation: Department of Dermatology, Radboud University Medical Centre, Nijmegen, the Netherlands.|Radboud University Nijmegen, the Netherlands.
authors.forename: E M
authors.initials: EM
authors.lastname: de Jong
authors.affiliation: Department of Dermatology, Ghent University Hospital, Ghent, Belgium.
authors.forename: J L W
authors.initials: JLW
authors.lastname: Lambert
authors.affiliation: Dermatology Unit, Azienda Ospedaliera San Donato, Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Malagoli
authors.affiliation: Department of Dermatology, University of Rome Tor Vergata, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bianchi
authors.affiliation: Dermatology Unit, Department of Biomedical Sciences, Humanitas University, Milan, Italy.|Skin Pathology Laboratory, Istituto Clinico Humanitas, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Costanzo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015331:Cohort Studies; D003879:Dermatologic Agents / Q000627:therapeutic use*; D005060:Europe; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome; D000069549:Ustekinumab / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D005819:Genetic Markers; D015236:HLA-C Antigens; C528994:HLA-C*06 antigen; D000069549:Ustekinumab