title: An update on the long-term safety experience of ustekinumab: results from the psoriasis clinical development program with up to four years of follow-up.
abstract: BACKGROUND
  The efficacy and safety profile of ustekinumab with up to three years of exposure suggested a favorable benefit-risk profile in patients with moderate to severe psoriasis.
  
  
  OBJECTIVE
  To evaluate the safety of ustekinumab in patients with moderate to severe psoriasis treated for up to four years.
  
  
  METHODS
  Safety data were pooled across four Phase II/III randomized controlled trials. Rates over time and cumulative rates of adverse events (AEs), AEs leading to treatment discontinuation, serious adverse events (SAEs), serious infections, malignancies, and major adverse cardiovascular events (MACE) (i.e., cardiovascular death, myocardial infarction [MI], or stroke as adjudicated by an independent panel of academic cardiologists) were evaluated. Observed rates of AEs of interest were compared with those expected in the general (malignancies, MI, and stroke) and psoriasis (serious infections, MI, and stroke) populations.
  
  
  RESULTS
  Overall, 3,117 patients were followed for up to four years (6,791 patient-years). Rates of AEs, AEs leading to treatment discontinuation, and SAEs remained stable over time, whereas cumulative rates were generally comparable between patients who received 45 mg and 90 mg of ustekinumab. The rates of AEs of interest also remained stable over time, and cumulative rates per 100 patient-years were 0.80 and 1.32 (serious infections), 0.70 and 0.53 (nonmelanoma skin cancer), 0.63 and 0.61 (other malignancies), and 0.56 and 0.46 (MACE) in patients treated with 45 mg and 90 mg, respectively. Rates of AEs of interest were consistent with those in the general and psoriasis populations.
  
  
  CONCLUSIONS
  The safety profile of long-term ustekinumab treatment with up to four years of continuous use remains consistent with previous reports, with no evidence of cumulative toxicity.
authors.affiliation: Dermatologikum Hamburg, Germany. reich@dermatologikum.de
authors.forename: Kristian
authors.initials: K
authors.lastname: Reich
authors.forename: Kim A
authors.initials: KA
authors.lastname: Papp
authors.forename: Christopher E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: Philippe O
authors.initials: PO
authors.lastname: Szapary
authors.forename: Newman
authors.initials: N
authors.lastname: Yeilding
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Wasfi
authors.forename: Elyssa
authors.initials: E
authors.lastname: Ott
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Hsu
authors.forename: Mark
authors.initials: M
authors.lastname: Lebwohl
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Gordon
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018592:Cross-Over Studies; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D013997:Time Factors; D000069549:Ustekinumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; D000069549:Ustekinumab