title: Clinical efficacy and safety maintained up to 5 years in patients with rheumatoid arthritis treated with tocilizumab in a randomised trial.
abstract: OBJECTIVE
  To report 5-year efficacy and safety in rheumatoid arthritis (RA) patients with active disease treated with tocilizumab.
  
  
  METHODS
  LITHE was a 2-year, randomised, placebo-controlled study of tocilizumab in RA patients (ClinicalTrials.gov, NCT00106535), with an additional 3-year, open-label extension. Patients were randomly assigned to tocilizumab (4 or 8 mg/kg IV) or placebo every 4 weeks + methotrexate. They could receive rescue with tocilizumab from week 16; after week 52, patients could switch to open-label tocilizumab 8 mg/kg. Radiographs were analysed by randomized treatment using the Genant-modified Total Sharp Score (GmTSS). Patients with at least baseline, week 104 and post-week 104 radiographs were included. Clinical and safety data were pooled for all patients who received ≥1 dose of tocilizumab; results are presented from the first tocilizumab dose.
  
  
  RESULTS
  1,149 patients were included with 4,380 patient-years of exposure; 34% received 5 years of treatment. Mean 5-year change in GmTSS revealed greater inhibition of radiographic progression in tocilizumab patients than placebo patients (1.34 vs. 3.02), with the greatest annualised progression rate in year 1. Overall, 53% of tocilizumab and 35% of placebo patients experienced no progression (GmTSS ≤0). Clinical benefit was maintained - determined by ACR response, DAS28-ESR <2.6, EULAR good/moderate response and Boolean remission - as was physical function. The safety profile over 5 years was similar to that over 2 years.
  
  
  CONCLUSIONS
  Over 5 years, tocilizumab + MTX inhibited radiographic progression and maintained improvements in signs and symptoms and physical function in MTX-inadequate responders with active disease; no new safety signals occurred.
authors.affiliation: Albany Medical College, Albany, New York, USA. jkremer@joint-docs.com.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Kremer
authors.affiliation: Hospital Marques de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Blanco
authors.affiliation: Panorama Medical Center, Cape Town, South Africa.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Halland
authors.affiliation: Rheumatology and Internal Diseases Clinic, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Brzosko
authors.affiliation: Hospital General de México and Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Ruben
authors.initials: R
authors.lastname: Burgos-Vargas
authors.affiliation: Roche Products Ltd., Welwyn Garden City, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Mela
authors.affiliation: Roche Products Ltd., Welwyn Garden City, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Rowell
authors.affiliation: Metroplex Clinical Research Center, Dallas, Texas, USA.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Fleischmann
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000188:drug therapy*; D001175:Arthrography; D001799:Blood Sedimentation; D004185:Disability Evaluation; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007596:Joints / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D012074:Remission Induction; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate