title: Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial.
abstract: BACKGROUND
  Interleukin 17A is a proinflammatory cytokine that is implicated in the pathogenesis of psoriatic arthritis. We assessed the efficacy and safety of subcutaneous secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis.
  
  
  METHODS
  In this phase 3, double-blind, placebo-controlled study undertaken at 76 centres in Asia, Australia, Canada, Europe, and the USA, adults (aged ≥18 years old) with active psoriatic arthritis were randomly allocated in a 1:1:1:1 ratio with computer-generated blocks to receive subcutaneous placebo or secukinumab 300 mg, 150 mg, or 75 mg once a week from baseline and then every 4 weeks from week 4. Patients and investigators were masked to treatment assignment. The primary endpoint was the proportion of patients achieving at least 20% improvement in the American College of Rheumatology response criteria (ACR20) at week 24. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01752634.
  
  
  RESULTS
  Between April 14, and Nov 25, 2013, 397 patients were randomly assigned to receive secukinumab 300 mg (n=100), 150 mg (n=100), 75 mg (n=99), or placebo (n=98). A significantly higher proportion of patients achieved an ACR20 at week 24 with secukinumab 300 mg (54 [54%] patients; odds ratio versus placebo 6·81, 95% CI 3·42-13·56; p<0·0001), 150 mg (51 [51%] patients; 6·52, 3·25-13·08; p<0·0001), and 75 mg (29 [29%] patients; 2·32, 1·14-4·73; p=0·0399) versus placebo (15 [15%] patients). Up to week 16, the most common adverse events were upper respiratory tract infections (four [4%], eight [8%], ten [10%], and seven [7%] with secukinumab 300 mg, 150 mg, 75 mg, and placebo, respectively) and nasopharyngitis (six [6%], four [4%], six [6%], and eight [8%], respectively). Serious adverse events were reported by five (5%), one (1%), and four (4%) patients in the secukinumab 300 mg, 150 mg, and 75 mg groups, respectively, compared with two (2%) in the placebo group. No deaths were reported.
  
  
  CONCLUSIONS
  Subcutaneous secukinumab 300 mg and 150 mg improved the signs and symptoms of psoriatic arthritis, suggesting that secukinumab is a potential future treatment option for patients with this disorder.
  
  
  BACKGROUND
  Novartis.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. Electronic address: Iain.McInnes@glasgow.ac.uk.
authors.forename: Iain B
authors.initials: IB
authors.lastname: McInnes
authors.affiliation: Swedish Medical Center and University of Washington, Seattle, WA, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.affiliation: Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: Bruce
authors.initials: B
authors.lastname: Kirkham
authors.affiliation: Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, San Diego School of Medicine, San Diego, CA, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Kavanaugh
authors.affiliation: Allergy/Immunology and Rheumatology Division, University of Rochester, Rochester, NY, USA.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Ritchlin
authors.affiliation: Memorial University, Newfoundland, NL, Canada.
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
authors.affiliation: Amsterdam Rheumatology and Immunology Center, Amsterdam, and Atrium Medical Center, Heerlen, Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.affiliation: NIHR Leeds Musculoskeletal Biomedical Research Unit and University of Leeds, Leeds, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Conaghan
authors.affiliation: Department of Dermatology, Tufts Medical Center, Boston, MA, USA.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Gottlieb
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: Hanno
authors.initials: H
authors.lastname: Richards
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Luminita
authors.initials: L
authors.lastname: Pricop
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Ligozio
authors.affiliation: Novartis Healthcare, Hyderabad, India.
authors.forename: Manmath
authors.initials: M
authors.lastname: Patekar
authors.affiliation: Novartis Pharma, Basel, Switzerland.
authors.forename: Shephard
authors.initials: S
authors.lastname: Mpofu
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D020381:Interleukin-17; C555450:secukinumab