title: Ustekinumab, an anti-IL-12/23 p40 monoclonal antibody, inhibits radiographic progression in patients with active psoriatic arthritis: results of an integrated analysis of radiographic data from the phase 3, multicentre, randomised, double-blind, placebo-controlled PSUMMIT-1 and PSUMMIT-2 trials.
abstract: OBJECTIVE
  Evaluate ustekinumab, an anti-interleukin (IL)-12 and IL-23 antibody, effects on radiographic progression in psoriatic arthritis (PsA).
  
  
  METHODS
  We conducted preplanned integrated analyses of combined radiographic data from PSUMMIT-1 and PSUMMIT-2 phase 3, randomised, controlled trials. Patients had active PsA despite prior conventional and/or biologic disease-modifying antirheumatic drugs (≥5/66 swollen, ≥5/68 tender joints, C-reactive protein ≥3.0 mg/L, documented plaque psoriasis). Patients (PSUMMIT-1, n=615; PSUMMIT-2, n=312) were randomised to ustekinumab 45 mg, 90 mg, or placebo, at weeks (wk) 0, 4 and every (q) 12 wks. At wk 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape. All other placebo patients received ustekinumab 45 mg at wk 24 and wk 28, then q 12 wks. Radiographs of hands/feet at wks 0/24/52 were assessed using PsA-modified van der Heijde-Sharp (vdH-S) scores; combined PSUMMIT-1 and PSUMMIT-2 changes in total vdH-S scores from wk 0 to wk 24 comprised the prespecified primary radiographic analysis. Treatment effects were assessed using analysis of variance on van der Waerden normal scores (factors=treatment, baseline methotrexate usage, and study).
  
  
  RESULTS
  Integrated data analysis results indicated that ustekinumab-treated patients (regardless of dose) demonstrated significantly less radiographic progression at wk 24 than did placebo recipients (wk 0-24 total vdH-S score mean changes: 0.4-combined/individual ustekinumab dose groups, 1.0-placebo; all p<0.02). From wk 24 to wk 52, inhibition of radiographic progression was maintained for ustekinumab-treated patients, and progression was substantially reduced among initial placebo recipients who started ustekinumab at wk 16 or wk 24 (wk 24 - wk 52, total vdH-S score mean change: 0.08).
  
  
  CONCLUSIONS
  Ustekinumab 45 and 90 mg treatments significantly inhibited radiographic progression of joint damage in patients with active PsA.
authors.affiliation: Rheumatology Allergy and Immunology Division, University of California-San Diego, , La Jolla, California, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: Christopher
authors.initials: C
authors.lastname: Ritchlin
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.forename: Lluis
authors.initials: L
authors.lastname: Puig
authors.forename: Alice B
authors.initials: AB
authors.lastname: Gottlieb
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Lenore
authors.initials: L
authors.lastname: Noonan
authors.forename: Carrie
authors.initials: C
authors.lastname: Brodmerkel
authors.forename: Michael
authors.initials: M
authors.lastname: Song
authors.forename: Alan M
authors.initials: AM
authors.lastname: Mendelsohn
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000000981:diagnostic imaging / Q000188:drug therapy*; D018592:Cross-Over Studies; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D033023:Foot Joints / Q000000981:diagnostic imaging*; D050823:Hand Joints / Q000000981:diagnostic imaging*; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000037:antagonists & inhibitors*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011859:Radiography; D016896:Treatment Outcome; D000069549:Ustekinumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053762:Interleukin-12 Subunit p40; D000069549:Ustekinumab; D008727:Methotrexate
keywords: Anti-TNF; Psoriatic Arthritis; Spondyloarthritis