title: Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study.
abstract: OBJECTIVE
  To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX).
  
  
  METHODS
  In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology-European League Against Rheumatism (OMERACT-EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT-EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2-5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy.
  
  
  RESULTS
  Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2-5): -0.7 (95% CIs -1.2 to -0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8.
  
  
  CONCLUSIONS
  In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment.
  
  
  BACKGROUND
  NCT00767325.
authors.affiliation: Service de Rhumatologie, APHP, Hôpital Ambroise Paré, Boulogne-Billancourt, France Laboratoire d'Excellence INFLAMEX, INSERM U1173, Université Paris Ouest-Versailles Saint-Quentin, Saint-Quentin-en-Yvelines, France.
authors.forename: Maria-Antonietta
authors.initials: MA
authors.lastname: D'Agostino
authors.affiliation: NIHR Leeds Musculoskeletal Biomedical Research Unit (LMBRU), Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wakefield
authors.affiliation: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Hilde
authors.initials: H
authors.lastname: Berner-Hammer
authors.affiliation: Department of Rheumatology and CIC-CRB-1404, Inserm U905, Rouen University Hospital, Rouen University, Rouen, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Vittecoq
authors.affiliation: Department of Medicine, Surgery and Neurosciences, Rheumatology Section, University of Siena, Siena, Italy.
authors.forename: Georgios
authors.initials: G
authors.lastname: Filippou
authors.affiliation: 3rd Rheumatology Department, National Institute of Rheumatology and Physiotherapy, Budapest, Hungary.
authors.forename: Peter
authors.initials: P
authors.lastname: Balint
authors.affiliation: Department of Rheumatology, Instituto Poal, Barcelona, Spain.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Möller
authors.affiliation: Rheumatology Unit, Dipartimento Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Roma, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Iagnocco
authors.affiliation: Department of Rheumatology, Hospital GU Gregorio Marañón, Madrid, Spain.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Naredo
authors.affiliation: Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Department of Epidemiology and Biostatistics, The Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Amsterdam, Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Boers
authors.affiliation: Medical Affairs, Bristol-Myers Squibb, Rueil-Malmaison, France.
authors.forename: Corine
authors.initials: C
authors.lastname: Gaillez
authors.affiliation: Global Clinical Operations and Strategy, Bristol-Myers Squibb, Braine-L'Alleud, Belgium.
authors.forename: Karina
authors.initials: K
authors.lastname: Van Holder
authors.affiliation: Medical Affairs, Bristol-Myers Squibb, Rueil-Malmaison, France.
authors.forename: Manuela
authors.initials: M
authors.lastname: Le Bars
mesh_terms: D000069594:Abatacept / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D015415:Biomarkers / Q000032:analysis; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D007596:Joints / Q000000981:diagnostic imaging; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012720:Severity of Illness Index; D013585:Synovitis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000209:etiology; D016896:Treatment Outcome; D018608:Ultrasonography, Doppler / Q000379:methods*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D000069594:Abatacept; D008727:Methotrexate
keywords: DMARDs (biologic); Disease Activity; Rheumatoid Arthritis; Ultrasonography