title: ASDAS, BASDAI and different treatment responses and their relation to biomarkers of inflammation, cartilage and bone turnover in patients with axial spondyloarthritis treated with TNFα inhibitors.
abstract: OBJECTIVE
  To investigate the relation between ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis disease activity index (BASDAI) and treatment response and biomarkers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), YKL-40), angiogenesis (vascular endothelial growth factor (VEGF)), cartilage (C-terminal crosslinking telopeptide of type II collagen (CTX-II), matrix metalloproteinase-3 (MMP-3), total aggrecan, cartilage oligomeric matrix protein) and bone (C-terminal crosslinking telopeptide of type I collagen, osteocalcin) turnover in 60 patients with axial spondyloarthritis initiating tumour necrosis factor alpha (TNFα) inhibitor therapy.
  
  
  METHODS
  ASDAS (CRP-based), BASDAI and biomarkers were determined before and seven times during 46 weeks of TNFα inhibitor therapy.
  
  
  RESULTS
  Very high ASDAS were associated with high levels of inflammatory biomarkers, while high BASDAI were not related to any biomarkers. Mixed modeling demonstrated significant longitudinal associations between ASDAS and IL-6, VEGF, MMP-3 and osteocalcin and between BASDAI and CRP, IL-6 and VEGF. Major improvement in ASDAS was associated with larger percentage decreases in biomarkers of inflammation, angiogenesis, MMP-3 and increases in aggrecan and osteocalcin. BASDAI response was associated with larger decreases in CRP and IL-6. Biomarkers with moderate/high differences in responsiveness for major versus no/clinically important improvement in ASDAS were CRP, IL-6, VEGF, aggrecan and osteocalcin, and VEGF and CTX-II for BASDAI response versus non-response.
  
  
  CONCLUSIONS
  Levels and changes of 10 biomarkers in patients with axial spondyloarthritis during anti-TNFα therapy were documented. Construct validity and responsiveness of IL-6, VEGF, MMP-3, total aggrecan and osteocalcin were demonstrated. ASDAS was more associated with these biomarkers than BASDAI, and may better reflect the inflammatory disease processes. ClinicalTrials.gov identifier NCT00133315.
authors.affiliation: Rheumatologic Research Unit, Glostrup University Hospital, Copenhagen, Denmark. susanne_juhl_ped@dadlnet.dk
authors.forename: Susanne Juhl
authors.initials: SJ
authors.lastname: Pedersen
authors.forename: Inge Juul
authors.initials: IJ
authors.lastname: Sørensen
authors.forename: Patrick
authors.initials: P
authors.lastname: Garnero
authors.forename: Julia Sidenius
authors.initials: JS
authors.lastname: Johansen
authors.forename: Ole Rintek
authors.initials: OR
authors.lastname: Madsen
authors.forename: Niels
authors.initials: N
authors.lastname: Tvede
authors.forename: Michael Sejer
authors.initials: MS
authors.lastname: Hansen
authors.forename: Gorm
authors.initials: G
authors.lastname: Thamsborg
authors.forename: Lis Smedegaard
authors.initials: LS
authors.lastname: Andersen
authors.forename: Ole
authors.initials: O
authors.lastname: Majgaard
authors.forename: Anne Gitte
authors.initials: AG
authors.lastname: Loft
authors.forename: Jon
authors.initials: J
authors.lastname: Erlendsson
authors.forename: Karsten
authors.initials: K
authors.lastname: Asmussen
authors.forename: Anne Grethe
authors.initials: AG
authors.lastname: Jurik
authors.forename: Jakob
authors.initials: J
authors.lastname: Møller
authors.forename: Maria
authors.initials: M
authors.lastname: Hasselquist
authors.forename: Dorrit
authors.initials: D
authors.lastname: Mikkelsen
authors.forename: Thomas
authors.initials: T
authors.lastname: Skjødt
authors.forename: Robert
authors.initials: R
authors.lastname: Lambert
authors.forename: Annette
authors.initials: A
authors.lastname: Hansen
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
mesh_terms: D000328:Adult; D043925:Angiogenesis Inducing Agents / Q000097:blood; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D002097:C-Reactive Protein / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D025241:Spondylarthritis / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D043925:Angiogenesis Inducing Agents; D018501:Antirheumatic Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein