title: Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis.
abstract: BACKGROUND
  In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an anti-interleukin-17A monoclonal antibody, in such patients.
  
  
  METHODS
  In this double-blind, phase 3 study, 606 patients with psoriatic arthritis were randomly assigned in a 1:1:1 ratio to receive intravenous secukinumab (at a dose of 10 mg per kilogram) at weeks 0, 2, and 4, followed by subcutaneous secukinumab at a dose of either 150 mg or 75 mg every 4 weeks, or placebo. Patients in the placebo group were switched to subcutaneous secukinumab at a dose of 150 mg or 75 mg at week 16 or 24, depending on clinical response. The primary end point was the proportion of patients with an American College of Rheumatology 20 (ACR20) response at week 24, defined as a 20% improvement from baseline in the number of tender and swollen joints and at least three other important domains.
  
  
  RESULTS
  ACR20 response rates at week 24 were significantly higher in the group receiving secukinumab at doses of 150 mg (50.0%) and 75 mg (50.5%) than in those receiving placebo (17.3%) (P<0.001 for both comparisons with placebo). Secondary end points, including the ACR50 response and joint structural damage, were significantly better in the secukinumab groups than in the placebo group. Improvements were sustained through 52 weeks. Infections, including candida, were more common in the secukinumab groups. Throughout the study (mean secukinumab exposure, 438.5 days; mean placebo exposure, 128.5 days), four patients in the secukinumab groups had a stroke (0.6 per 100 patient-years; 95% confidence interval [CI], 0.2 to 1.5), and two had a myocardial infarction (0.3 per 100 patient-years; 95% CI, 0.0 to 1.0), as compared with no patients in the placebo group.
  
  
  CONCLUSIONS
  Secukinumab was more effective than placebo in patients with psoriatic arthritis, which validates interleukin-17A as a therapeutic target. Infections were more common in the secukinumab groups than in the placebo group. The study was neither large enough nor long enough to evaluate uncommon serious adverse events or the risks associated with long-term use. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT01392326.).
authors.affiliation: From the Swedish Medical Center and the University of Washington - both in Seattle (P.J.M.); University of Glasgow, Glasgow (I.B.M.), and Guy's and St. Thomas' NHS Foundation Trust, London (B.K.) - both in the United Kingdom; University of California, San Diego, School of Medicine, San Diego (A.K.); Memorial University, St. John's, NL, Canada (P.R.); Leiden University Medical Center, Leiden (D.H.), and University of Amsterdam and Atrium Medical Center, Amsterdam (R.L.) - all in the Netherlands; University of Queensland, Brisbane, Australia (P.N.); Novartis Pharmaceuticals, East Hanover, NJ (L.P., J.Y.); and Novartis Pharma, Basel, Switzerland (H.B.R., S.M.).
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.forename: Bruce
authors.initials: B
authors.lastname: Kirkham
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.forename: Peter
authors.initials: P
authors.lastname: Nash
authors.forename: Luminita
authors.initials: L
authors.lastname: Pricop
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Yuan
authors.forename: Hanno B
authors.initials: HB
authors.lastname: Richards
authors.forename: Shephard
authors.initials: S
authors.lastname: Mpofu
mesh_terms: D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D015535:Arthritis, Psoriatic / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D012141:Respiratory Tract Infections / Q000209:etiology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D020381:Interleukin-17; C555450:secukinumab