title: Radiographic progression is associated with resolution of systemic inflammation in patients with axial spondylarthritis treated with tumor necrosis factor α inhibitors: a study of radiographic progression, inflammation on magnetic resonance imaging, and circulating biomarkers of inflammation, angiogenesis, and cartilage and bone turnover.
abstract: OBJECTIVE
  To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor α (TNFα) inhibitor therapy.
  
  
  METHODS
  MRIs were evaluated according to the Berlin sacroiliac (SI) joint and spine inflammation scoring method at baseline, week 22, and week 46. Radiographs were evaluated using the modified Stoke Ankylosing Spondylitis Spine Score at baseline and week 46. Patients with new syndesmophytes were identified. Biomarker levels in patients were compared to levels in healthy subjects.
  
  
  RESULTS
  Higher pretreatment MRI inflammation scores for SI joints and/or lumbar spine were associated with higher baseline CTX-II levels, but not with higher levels of biomarkers of inflammation and bone turnover. During treatment with TNFα inhibitors, a decrease in MRI inflammation scores from baseline to week 22 was associated with larger percentage decreases in and a normalization of CRP and IL-6 levels as compared to an increase or no change in MRI scores. Development of new syndesmophytes was associated with larger percentage decreases in CRP and IL-6 levels and an increase in osteocalcin level, and with normalization of CRP and IL-6 levels from baseline to week 22. Persistent systemic inflammation was associated with radiographic nonprogression.
  
  
  CONCLUSIONS
  Our findings indicate that inflammation on baseline MRI is associated with higher CTX-II levels. Radiographic progression is associated with decreased systemic inflammation, as assessed by IL-6 and CRP levels and MRI, supporting the notion of a link between the resolution of inflammation and new bone formation in SpA patients during anti-TNFα therapy.
authors: Department of Rheumatology C Post 535, Gentofte University Hospital, Copenhagen, Denmark. susanne_juhl_ped@dadlnet.dk
authors: Susanne Juhl
authors: SJ
authors: Pedersen
authors: Inge Juul
authors: IJ
authors: Sørensen
authors: Robert G W
authors: RG
authors: Lambert
authors: Kay-Geert A
authors: KG
authors: Hermann
authors: Patrick
authors: P
authors: Garnero
authors: Julia Sidenius
authors: JS
authors: Johansen
authors: Ole Rintek
authors: OR
authors: Madsen
authors: Annette
authors: A
authors: Hansen
authors: Michael Sejer
authors: MS
authors: Hansen
authors: Gorm
authors: G
authors: Thamsborg
authors: Lis Smedegaard
authors: LS
authors: Andersen
authors: Ole
authors: O
authors: Majgaard
authors: Anne Gitte
authors: AG
authors: Loft
authors: Jon
authors: J
authors: Erlendsson
authors: Karsten H
authors: KH
authors: Asmussen
authors: Anne Grethe
authors: AG
authors: Jurik
authors: Jakob
authors: J
authors: Møller
authors: Maria
authors: M
authors: Hasselquist
authors: Dorrit
authors: D
authors: Mikkelsen
authors: Mikkel
authors: M
authors: Østergaard
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism*; D064236:Cartilage Oligomeric Matrix Protein; D016022:Case-Control Studies; D015331:Cohort Studies; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging* / Q000473:pathology*; D000069285:Infliximab; D015850:Interleukin-6 / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D064235:Matrilin Proteins; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood*; D015675:Osteocalcin / Q000097:blood; D011446:Prospective Studies; D011859:Radiography; D025241:Spondylarthritis / Q000097:blood / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D015850:Interleukin-6; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D015675:Osteocalcin; D002097:C-Reactive Protein; D000069285:Infliximab; D019278:Matrix Metalloproteinase 3; D000068879:Adalimumab