title: Which spinal lesions are associated with new bone formation in patients with ankylosing spondylitis treated with anti-TNF agents? A long-term observational study using MRI and conventional radiography.
abstract: OBJECTIVE
  To study the relationship of spinal inflammation and fatty degeneration (FD) as detected by MRI and new bone formation seen on conventional radiographs (CRs) in ankylosing spondylitis (AS).
  
  
  METHODS
  CRs at baseline, 2 years and 5 years and spinal MRIs at baseline and 2 years of 73 AS patients treated with infliximab in European AS Infliximab Cohort were available. Relative risks (RR) were calculated with a general linear model after adjustment for within-patient variation.
  
  
  RESULTS
  In a total of 1466 vertebral edges (VEs) without baseline syndesmophytes, 61 syndesmophytes developed at 5 years, the majority of which (57.4%) had no corresponding detectable MRI lesions at baseline. VEs with both inflammation and FD at baseline had the highest risk (RR 3.3, p=0.009) for syndesmophyte formation at 5 years, followed by VEs that developed new FD or did not resolve FD at 2 years (RR=2.3, p=0.034), while inflammation at baseline with no FD at 2 years had the lowest risk for syndesmophyte formation at 5 years (RR=0.8). Of the VEs with inflammation at baseline, >70% resolved completely, 28.8% turned into FD after 2 years, but only 1 syndesmophyte developed within 5 years.
  
  
  CONCLUSIONS
  Parallel occurrence of inflammation and FD at baseline and development of FD without prior inflammation after 2 years were significantly associated with syndesmophyte formation after 5 years of anti-tumour necrosis factor (TNF) therapy. However, the sequence 'inflammation-FD-new bone formation' was rarely observed, an argument against the TNF-brake hypothesis. Whether an early suppression of inflammation leads to a decrease of the risk for new bone formation remains to be demonstrated.
authors.affiliation: Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Germany.
authors.forename: X
authors.initials: X
authors.lastname: Baraliakos
authors.affiliation: Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Heldmann
authors.affiliation: Epidemiology Unit, German Rheumatism Research Center, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Callhoff
authors.affiliation: Epidemiology Unit, German Rheumatism Research Center, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Listing
authors.affiliation: Hopital Erasme, Brussels, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Appelboom
authors.affiliation: Rheumapraxis Steglitz/Charité, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Brandt
authors.affiliation: Department of Rheumatology, Universitair Ziekenhuis Ghent, Gent, Belgium.
authors.forename: F
authors.initials: F
authors.lastname: Van den Bosch
authors.affiliation: Department of Rheumatology, Hopital Ambroise Paré, University of Versailles Saint-Quentin-en-Yvelines, Boulogne, France.
authors.forename: M
authors.initials: M
authors.lastname: Breban
authors.affiliation: Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Campus Mitte, Berlin, Germany.
authors.forename: Gr
authors.initials: G
authors.lastname: Burmester
authors.affiliation: Department of Rheumatology B, Paris-Descartes University; AP-HP, Cochin Hospital, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Dougados
authors.affiliation: Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, and NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: P
authors.initials: P
authors.lastname: Emery
authors.affiliation: Department of Rheumatology, Addenbrookes Hospital, University of Cambridge, Cambridge, UK.
authors.forename: H
authors.initials: H
authors.lastname: Gaston
authors.affiliation: Medizinische Klinik und Poliklinik IV, University of Munich, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Grunke
authors.affiliation: Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: I E
authors.initials: IE
authors.lastname: Van Der Horst-Bruinsma
authors.affiliation: Department of Clinical immunology & Rheumatology, AMC Amsterdam, Academisch Ziekenhuis Maastricht, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Landewé
authors.affiliation: Department of Medicine, Division of Rheumatology, University Central Hospital Helsinki, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Leirisalo-Repo
authors.affiliation: Medical Department I, Rheumatology, Charité University Medicine Berlin, Campus Steglitz, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Sieper
authors.affiliation: University Hospital Leuven, Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: De Vlam
authors.affiliation: Center for Orthopaedics and Traumatology, St. Anna Hospital, Herne, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Pappas
authors.affiliation: Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Kiltz
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: Van Der Heijde
authors.affiliation: Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Braun
mesh_terms: D000273:Adipose Tissue / Q000473:pathology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000209:etiology; D000069285:Infliximab; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009999:Ossification, Heterotopic / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D011379:Prognosis; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab
keywords: Ankylosing Spondylitis; Anti-TNF; Magnetic Resonance Imaging