title: Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1.
abstract: OBJECTIVE
  To assess the safety and efficacy of ixekizumab, a monoclonal antibody that inhibits interleukin-17A, in a double-blind phase III trial enrolling patients with active psoriatic arthritis (PsA).
  
  
  METHODS
  Patients naive to biologic therapy with active PsA were randomised to subcutaneous injections of placebo (N=106), adalimumab 40 mg once every 2 weeks (active reference; N=101), ixekizumab 80 mg once every 2 weeks (IXEQ2W) (N=103), or ixekizumab 80 mg once every 4 weeks (IXEQ4W) (N=107). Both ixekizumab regimens included a 160-mg starting dose. The primary objective was to assess the superiority of IXEQ2W or IXEQ4W versus placebo as measured by the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 24.
  
  
  RESULTS
  Significantly more patients treated with ixekizumab achieved an ACR20 response with IXEQ2W (62.1%) or IXEQ4W (57.9%) than placebo (30.2%) (p≤0.001; non-responder imputation method). Disease activity and functional disability were significantly improved with both ixekizumab doses versus placebo at weeks 12 and 24, and there was significantly less progression of structural damage at week 24 (p≤0.01). Clearance of plaque psoriasis was greater with ixekizumab than placebo (p≤0.001). Efficacy results with adalimumab, the active reference arm, showed significant improvements versus placebo. Treatment-emergent adverse events were more frequent with ixekizumab (65.7-66.4%) and adalimumab (64.4%) than placebo (47.2%) (p<0.05).
  
  
  CONCLUSIONS
  In biologic-naive patients with active PsA, ixekizumab treatment resulted in improvements in disease activity and physical function, as well as in the inhibition of structural damage progression. Overall, adverse events were more frequent in all active groups compared with placebo.
  
  
  BACKGROUND
  NCT01695239; EudraCT2011-002326-49; Results.
authors.affiliation: Department of Rheumatology, Swedish Medical Center, and University of Washington, Seattle, Washington, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Désirée
authors.identifier: http://orcid.org/0000-0002-5781-158X
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Allergy, Immunology, & Rheumatology Division, University of Rochester Medical Center, Rochester, New York, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Ritchlin
authors.affiliation: Immuno-Rheumatology Center, St. Luke's International Hospital, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Okada
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana, USA.|Rheumatology Division, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Cuchacovich
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Shuler
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors.forename: Chen-Yen
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Braun
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana, USA.
authors.forename: Chin H
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Dafna D
authors.initials: DD
authors.lastname: Gladman
mesh_terms: D000068879:Adalimumab / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D020381:Interleukin-17; C549079:ixekizumab; D000068879:Adalimumab
keywords: DMARDs (biologic); Psoriatic Arthritis; Spondyloarthritis; Treatment