title: Continued benefit of tocilizumab plus disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis and inadequate clinical responses by week 8 of treatment.
abstract: OBJECTIVE
  To evaluate whether patients with rheumatoid arthritis who did not respond sufficiently to tocilizumab (TCZ) plus disease-modifying antirheumatic drug (DMARD) treatment by Week 8 responded at later timepoints when continuing to take their original dose of TCZ.
  
  
  METHODS
  In this posthoc analysis of data from phase III randomized controlled trials of inadequate responders (IR) to DMARD or tumor necrosis factor-α inhibitors (anti-TNF), percentages of patients meeting early response criteria were calculated by randomized treatment arm (TCZ 4 mg/kg, 8 mg/kg, or placebo in combination with DMARD). Percentages of patients achieving certain disease activity thresholds at later timepoints were calculated for patients who had/had not achieved response by Week 8.
  
  
  RESULTS
  In DMARD-IR early nonresponders, 29.0%, 17.2%, and 3.7% of TCZ 8 mg/kg-randomized, TCZ 4 mg/kg-randomized, and placebo-randomized patients, respectively, achieved 28-joint Disease Activity Score (DAS28) ≤ 3.2 by Week 24. Among anti-TNF-IR patients without early response, 26.5%, 8.5%, and 1.9% of TCZ 8 mg/kg-randomized, TCZ 4 mg/kg-randomized, and placebo-randomized patients, respectively, achieved DAS28 ≤ 3.2 at Week 24.
  
  
  CONCLUSIONS
  A substantial number of DMARD-IR patients taking TCZ 4 or 8 mg/kg and anti-TNF-IR patients taking TCZ 8 mg/kg who failed to respond by 8 weeks benefited from continued TCZ treatment in combination with DMARD. In contrast, the anti-TNF-IR patients without early responses who continued to take TCZ 4 mg/kg were unlikely to experience a cumulative benefit. ClinicalTrials.gov registration numbers: NCT00106548, NCT00106574, NCT00106535, NCT00106522.
authors.affiliation: From Mount Sinai Hospital, The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Toronto, Ontario, Canada; US Medical Affairs-Immunology and Biometrics and Health Outcomes, Genentech, South San Francisco, California; University of Alabama at Birmingham, Division of Clinical Immunology and Rheumatology, Birmingham, Alabama, USA.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Keystone
authors.forename: Andrew
authors.initials: A
authors.lastname: Anisfeld
authors.forename: Sarika
authors.initials: S
authors.lastname: Ogale
authors.forename: Jenny N
authors.initials: JN
authors.lastname: Devenport
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C502936:tocilizumab; D008727:Methotrexate
keywords: ANTIRHEUMATIC AGENTS; MONOCLONAL ANTIBODIES; RHEUMATOID ARTHRITIS; TREATMENT OUTCOME