title: Radiographic benefit and maintenance of clinical benefit with intravenous golimumab therapy in patients with active rheumatoid arthritis despite methotrexate therapy: results up to 1 year of the phase 3, randomised, multicentre, double blind, placebo controlled GO-FURTHER trial.
abstract: OBJECTIVE
  Report on radiographic effects and maintenance of clinical benefit with intravenous golimumab 2 mg/kg+methotrexate (MTX) for up to week (wk) 52 in active rheumatoid arthritis (RA).
  
  
  METHODS
  Patients (n=592) with active RA (≥6/66 swollen, ≥6/68 tender joints, C reactive protein (CRP) ≥1.0 mg/dL and positive for rheumatoid factor and/or anticyclic citrullinated protein antibody at screening) despite MTX ≥3 months (stable dose of 15-25 mg/week for ≥4 weeks) participated in this multicentre, international, randomised, double blind, placebo controlled, phase 3 study. Patients were randomised (2:1) to receive intravenous golimumab 2 mg/kg or placebo infusions at weeks 0 and 4 and then every 8 weeks; patients continued their stable MTX regimen. Placebo patients started golimumab 2 mg/kg at wk16 (early escape; <10% improvement in tender and swollen joints) or wk24 (crossover by design). Week 24 and wk52 radiographic (van der Heijde-Sharp (vdH-S) scores), clinical efficacy and safety data up to 1 year are reported here.
  
  
  RESULTS
  Significant and rapid clinical improvement was observed up to wk24 of intravenous golimumab therapy. Golimumab+MTX treated patients demonstrated less radiographic progression than placebo treated patients at wk24 (vdH-S score mean change 0.03 vs 1.09; p<0.001) and wk52 (0.13 vs 1.22; p=0.001). Among patients with ≥20% improvement in the American College of Rheumatology response criteria or who achieved a 'good' or 'moderate' response according to the 28 joint Disease Activity Score employing CRP at wk24, approximately 80% maintained this response up until wk52. Through an average of 43.5 weeks of follow-up, 64.6% of patients receiving golimumab+MTX reported adverse events, most commonly non-serious infections.
  
  
  CONCLUSIONS
  In patients with active RA despite MTX, intravenous golimumab+MTX yielded significant inhibition of structural damage at wk24 and wk52, and sustained clinical improvement in signs and symptoms with no new safety signals up to 1 year.
  
  
  BACKGROUND
  NCT00973479, EudraCT 2008-006 064-11.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.affiliation: Department of Development and Regeneration KU Leuven, Skeletal Biology and Engineering Research Centre, Leuven, Belgium Department of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Rene
authors.initials: R
authors.lastname: Westhovens
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Mendelsohn
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Lilianne
authors.initials: L
authors.lastname: Kim
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Lo
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Shihong
authors.initials: S
authors.lastname: Sheng
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Lenore
authors.initials: L
authors.lastname: Noonan
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Lu
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Leu
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Baker
authors.affiliation: Johns Hopkins University Baltimore, Baltimore, Maryland, USA.
authors.forename: Clifton O
authors.initials: CO
authors.lastname: Bingham
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D033023:Foot Joints / Q000000981:diagnostic imaging*; D050823:Hand Joints / Q000000981:diagnostic imaging*; D006801:Humans; D060046:Maintenance Chemotherapy / Q000379:methods; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D011859:Radiography; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C529000:golimumab; D008727:Methotrexate
keywords: Methotrexate; Rheumatoid Arthritis; TNF-alpha