title: Retreatment with rituximab based on a treatment-to-target approach provides better disease control than treatment as needed in patients with rheumatoid arthritis: a retrospective pooled analysis.
abstract: OBJECTIVE
  To assess the efficacy and safety profiles of two different rituximab retreatment regimens in patients with RA.
  
  
  METHODS
  Four hundred and ninety-three RA patients with an inadequate response to MTX recruited into rituximab Phase II/III studies received further courses of open-label rituximab based on two approaches: (i) treatment to target (TT): patients assessed 24 weeks after each course and retreated if not in remission [DAS in 28 joints based on ESR (DAS-28-ESR) ≥ 2.6]; (ii) treatment as needed (PRN): patients retreated at the physician's discretion ≥24 weeks following the first course and ≥16 weeks following further courses, if both swollen and tender joint counts were ≥8. All courses consisted of i.v. rituximab 2 × 1000 mg 2 weeks apart plus MTX. Observed data were analysed according to treatment strategy.
  
  
  RESULTS
  Multiple courses of rituximab maintained or improved responses irrespective of regimen. TT provided tighter control of disease activity with significantly greater improvements in DAS-28-ESR and lower HAQ-disability index scores vs PRN. TT resulted in significantly more patients achieving major clinical response. PRN resulted in recurrence of disease symptoms between courses, with TT significantly reducing the incidence of RA flares. Despite more frequent retreatment with TT compared with PRN, the rates of serious adverse events and serious infections were comparable between regimens.
  
  
  CONCLUSIONS
  Retreatment with rituximab based on 24-week evaluations and to a target of DAS-28-ESR remission leads to improved efficacy and tighter control of disease activity compared with PRN without a compromised safety profile. TT may be the preferable rituximab treatment regimen for patients with RA.
authors.affiliation: Leeds Institute of Molecular Medicine, University of Leeds, Leeds LS7 4SA, UK. p.emery@leeds.ac.uk
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mease
authors.forename: Andrea
authors.initials: A
authors.lastname: Rubbert-Roth
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Curtis
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Norman B
authors.initials: NB
authors.lastname: Gaylis
authors.forename: Sarah
authors.initials: S
authors.lastname: Williams
authors.forename: Mark
authors.initials: M
authors.lastname: Reynard
authors.forename: Helen
authors.initials: H
authors.lastname: Tyrrell
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000628:therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D019233:Retreatment; D012189:Retrospective Studies; D000069283:Rituximab; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D000069283:Rituximab; D008727:Methotrexate