title: Certolizumab pegol plus methotrexate provides broad relief from the burden of rheumatoid arthritis: analysis of patient-reported outcomes from the RAPID 2 trial.
abstract: OBJECTIVE
  To assess the impact of certolizumab pegol (CZP) on patient-reported outcomes (PROs) in rheumatoid arthritis (RA), and to interpret these results using number needed to treat (NNT), and associations between PRO responses and longer term outcomes.
  
  
  METHODS
  A total of 619 patients with active RA were randomised to CZP 200 or 400 mg, or placebo plus methotrexate (MTX). PROs assessed included pain, patient's global assessment of disease activity (PtGA), physical function, fatigue and health-related quality of life. Treatment impact on PROs, NNT to achieve simultaneous improvements in multiple PROs and correlations between PROs were calculated. Times to onset of improvements greater than or equal to minimum clinically important differences (MCIDs) in pain as a determinant of clinical outcomes at week 24 were compared between week 6 and 12 responders, and in patients with improvements in pain ≥ MCID at week 12 (week 12 responders/non-responders).
  
  
  RESULTS
  CZP 200 and 400 mg plus MTX were associated with rapid, clinically meaningful improvements in all PROs. The NNT for subjects to report changes ≥MCID in up to five PROs was two to three, and five for all six PROs (pain, PtGA, physical function, fatigue and short-form 36-item Physical and Mental Component Summary Scores). More patients with improvements ≥MCID in pain at week 6 than those at week 12 had lower disease activity at week 24. Week 12 pain responders had better clinical outcomes at week 24 than non-responders.
  
  
  CONCLUSIONS
  The data demonstrate that CZP provides broad relief from the burden of RA. Trial registration number NCT00160602.
authors.affiliation: Division of Immunology and Rheumatology, Stanford University, 306 Ramona Road, Portola Valley, CA 94028, USA. vstrand@stanford.edu
authors.forename: Vibeke
authors.initials: V
authors.lastname: Strand
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.forename: Philip
authors.initials: P
authors.lastname: Mease
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.forename: Dinesh
authors.initials: D
authors.lastname: Khanna
authors.forename: Enkeleida
authors.initials: E
authors.lastname: Nikaï
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Coteur
authors.forename: Michael
authors.initials: M
authors.lastname: Schiff
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D000068582:Certolizumab Pegol; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005221:Fatigue / Q000209:etiology; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D010146:Pain / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007140:Immunoglobulin Fab Fragments; D011092:Polyethylene Glycols; D000068582:Certolizumab Pegol; D008727:Methotrexate