title: Long-term safety experience of ustekinumab in patients with moderate-to-severe psoriasis (Part I of II): results from analyses of general safety parameters from pooled Phase 2 and 3 clinical trials.
abstract: BACKGROUND
  Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate-to-severe psoriasis.
  
  
  OBJECTIVE
  To evaluate overall pooled study data to assess the safety profile of ustekinumab through 3 years of treatment.
  
  
  METHODS
  Cumulative safety data were pooled from studies in 3117 ustekinumab-treated patients.
  
  
  RESULTS
  During the placebo-controlled periods (Phase 2, PHOENIX 1, PHOENIX 2), rates of adverse events (AEs) were comparable among patients treated with placebo (50.4%), with ustekinumab 45 mg (57.6%), or with ustekinumab 90 mg (51.6%); similar findings were observed during the controlled period of the ACCEPT trial (etanercept: 70.0%; ustekinumab 45 mg: 66.0%; and ustekinumab 90 mg: 69.2%). Rates of serious AEs (SAEs) through the controlled periods were low and comparable among all groups (1.2% to 1.9%). Through 3 years, rates of AEs per 100 patient-years of follow-up (/100 patient-yrs) (45 mg: 305.2/100 patient-yrs; 90 mg: 305.9/100 patient-yrs) and SAEs (45 mg: 6.8/100 patient-yrs; 90 mg: 8.2/100 patient-yrs) were comparable between ustekinumab doses. No cases of demyelination or tuberculosis were reported in these trials. No dose response in rates of AEs, overall infections, or SAEs was apparent through 3 years. Rates of AEs, infections, SAEs, and AEs leading to study agent discontinuation remained generally stable or decreased over time.
  
  
  CONCLUSIONS
  Controlled periods did not extend beyond 12 to 20 weeks. Only 1247 of the 3117 ustekinumab-treated patients were treated for 2 or more years.
  
  
  CONCLUSIONS
  The safety profile of continued ustekinumab exposure through up to 3 years is favorable and consistent with previous short-term reports.
authors.affiliation: Mount Sinai School of Medicine, New York City, New York 10029, USA. Lebwohl@aol.com
authors.forename: Mark
authors.initials: M
authors.lastname: Lebwohl
authors.forename: Craig
authors.initials: C
authors.lastname: Leonardi
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Prinz
authors.forename: Philippe O
authors.initials: PO
authors.lastname: Szapary
authors.forename: Newman
authors.initials: N
authors.lastname: Yeilding
authors.forename: Cynthia
authors.initials: C
authors.lastname: Guzzo
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Hsu
authors.forename: Bruce
authors.initials: B
authors.lastname: Strober
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D000068800:Etanercept; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000175:diagnosis / Q000188:drug therapy*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D018570:Risk Assessment; D017751:Safety Management; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D000069549:Ustekinumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000069549:Ustekinumab; D000068800:Etanercept