title: The effect of bodyweight on the efficacy and safety of ixekizumab: results from an integrated database of three randomised, controlled Phase 3 studies of patients with moderate-to-severe plaque psoriasis.
abstract: BACKGROUND
  There is concern that increased bodyweight may impact efficacy of some therapies used to treat psoriasis.
  
  
  OBJECTIVE
  To evaluate the effect of bodyweight on response to ixekizumab treatment in patients with moderate-to-severe psoriasis.
  
  
  METHODS
  Patients were characterized under three bodyweight categories (<80 kg, 80 to <100 kg, ≥100 kg) in this preplanned subgroup analysis from an integrated database of three multicenter, randomised, double-blind, controlled Phase 3 clinical studies (UNCOVER-1, UNCOVER-2 and UNCOVER-3). In the first 12 weeks of each study, patients were randomly assigned to receive subcutaneous placebo, 80-mg ixekizumab every 2 weeks (IXE Q2W) or every 4 weeks (IXE Q4W) after a starting dose of 160-mg ixekizumab, or 50-mg etanercept twice weekly (UNCOVER-2 and UNCOVER-3 only).
  
  
  RESULTS
  This analysis included 3855 patients with baseline bodyweight in the IXE Q4W (N = 1159), IXE Q2W (N = 1168), placebo (N = 789) and etanercept (N = 739) groups. Distribution of patients across bodyweight categories was similar between treatment groups. Baseline demographics and patients characteristics were generally consistent across treatment groups within each bodyweight category. Across all bodyweight categories, a significantly higher percentage of patients treated with IXE Q2W or IXE Q4W than with placebo or etanercept achieved PASI 75, PASI 90 or PASI 100 at Week 12. No meaningful differences in PASI 75 response rates were observed across bodyweight categories. Some numerical differences in PASI 90 and PASI 100 response rates were observed between bodyweight categories with IXE Q2W providing numerically higher response rates than IXE Q4W. The incidence of treatment-emergent adverse events was similar in the treatment groups and across bodyweight categories.
  
  
  CONCLUSIONS
  Ixekizumab was efficacious in the treatment of moderate-to-severe psoriasis regardless of bodyweight. The safety profile of ixekizumab was also similar across bodyweight categories, and no safety signals were identified specific to any of the bodyweight categories.
authors.affiliation: Dermatologikum Hamburg and SCIderm Research Institute, Hamburg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Reich
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Puig
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mallbris
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: O
authors.initials: O
authors.lastname: Osuntokun
authors.affiliation: St. Louis University School of Medicine, St. Louis, MO, USA.
authors.forename: C
authors.initials: C
authors.lastname: Leonardi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight; D017326:Clinical Trials, Phase III as Topic; D003879:Dermatologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D000068800:Etanercept / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011565:Psoriasis / Q000188:drug therapy* / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003879:Dermatologic Agents; C549079:ixekizumab; D000068800:Etanercept