title: Tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate: LITHE study 2-year results.
abstract: OBJECTIVE
  To assess radiographic progression, physical function, clinical disease activity, and safety in patients with rheumatoid arthritis (RA) who had inadequate response to methotrexate (MTX) and who were treated with tocilizumab-MTX or MTX during Year 2 of a 2-year study.
  
  
  METHODS
  During Year 1, patients were randomized to placebo-MTX, 4 mg/kg tocilizumab-MTX, or 8 mg/kg tocilizumab-MTX. During Year 2, patients continued the initial double-blind treatment or switched to open-label 8 mg/kg tocilizumab-MTX. Co-primary endpoints at Week 104 were mean change from baseline in Genant-modified Total Sharp Score (GmTSS) and adjusted mean area under the curve (AUC) for change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI). Signs and symptoms of RA and safety were also evaluated.
  
  
  RESULTS
  At Week 104, mean change from baseline in GmTSS was significantly lower for patients initially randomized to tocilizumab-MTX 4 mg/kg (0.58; p = 0.0025) or 8 mg/kg (0.37; p < 0.0001) than for patients initially randomized to placebo-MTX (1.96). Adjusted mean AUC of change from baseline in HAQ-DI was also significantly lower in patients initially randomized to tocilizumab-MTX 4 mg/kg (-287.5; p < 0.0001) or 8 mg/kg (-320.8; p < 0.0001) than in patients initially randomized to placebo-MTX (-139.4). Signs and symptoms of RA were maintained or showed improvement. No new safety signals were noted.
  
  
  CONCLUSIONS
  Compared with placebo-MTX, tocilizumab-MTX significantly inhibited structural joint damage and improved physical function in patients with RA who previously had inadequate response to MTX. An extension of this study is continuing and will provide additional longterm efficacy and safety data. National Clinical Trials registry NCT00106535.
authors: Metroplex Clinic Research Center, Dallas, Texas, USA; Panorama Medical Center, Cape Town, South Africa. RFleischmann@arthdocs.com
authors: Roy M
authors: RM
authors: Fleischmann
authors: Anne-Marie
authors: AM
authors: Halland
authors: Marek
authors: M
authors: Brzosko
authors: Ruben
authors: R
authors: Burgos-Vargas
authors: Christopher
authors: C
authors: Mela
authors: Emma
authors: E
authors: Vernon
authors: Joel M
authors: JM
authors: Kremer
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* / Q000503:physiopathology; D004185:Disability Evaluation; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D006801:Humans; D007596:Joints / Q000187:drug effects*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000209:etiology; D011859:Radiography; D012720:Severity of Illness Index; D018434:Sickness Impact Profile; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate