title: Longterm safety and efficacy of tocilizumab in patients with rheumatoid arthritis: a cumulative analysis of up to 4.6 years of exposure.
abstract: OBJECTIVE
  To assess the longterm safety and efficacy of tocilizumab (TCZ) in patients with moderate to severe rheumatoid arthritis (RA).
  
  
  METHODS
  Patient data were from 5 randomized controlled TCZ trials (n = 4211), their open-label extension phases (n = 3512), and a drug interaction study (n = 23). All randomly assigned patients, regardless of previous RA treatment, were analyzed. Measures of safety included number of adverse events (AE), serious AE (SAE), AE leading to treatment discontinuation, laboratory tests, and deaths. Efficacy measures included American College of Rheumatology (ACR) 20/50/70 responses, tender joint count (TJC), swollen joint count (SJC), ACR core set components, and low disease activity (LDA) or Disease Activity Score in 28 joints (DAS28) remission. ACR/European League Against Rheumatism (EULAR) disease remission was a posthoc exploratory analysis.
  
  
  RESULTS
  Total duration of observation was 12,293 patient-years (PY). No new safety signals were identified; infections were the most common AE and SAE. The rate of serious infections was 4.5/100 PY. Improvements from baseline in clinical efficacy, measured as ACR20/50/70 responses, TJC, SJC, ACR core set components, and LDA and DAS28 remission, were generally sustained through at least 216 weeks of followup. ACR/EULAR disease remission was attained by 16.5% (Boolean) and 22.7% (index) of patients at Week 216.
  
  
  CONCLUSIONS
  TCZ has to date been studied for up to 4.6 years (240 weeks) of treatment in patients with RA. Our analysis reveals a longer-term safety profile consistent with previous observations, no new safety signals, and durable efficacy of TCZ in a large clinical trial program.
authors: Division of Rheumatology, Stanford University Medical Center, Palo Alto, CA 94304, USA. Genovese@stanford.edu
authors: Mark C
authors: MC
authors: Genovese
authors: Andrea
authors: A
authors: Rubbert-Roth
authors: Josef S
authors: JS
authors: Smolen
authors: Joel
authors: J
authors: Kremer
authors: Majed
authors: M
authors: Khraishi
authors: Juan
authors: J
authors: Gómez-Reino
authors: Anthony
authors: A
authors: Sebba
authors: Robert
authors: R
authors: Pilson
authors: Sarah
authors: S
authors: Williams
authors: Ronald
authors: R
authors: Van Vollenhoven
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab
keywords: RHEUMATOID ARTHRITIS; SAFETY; TOCILIZUMAB; TREATMENT EFFICACY