title: The effect of three years of TNFα blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study.
abstract: BACKGROUND
  The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-α) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS).
  
  
  METHODS
  This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-α blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly.
  
  
  RESULTS
  After three years, 72 patients (65%) were still using their first TNF-α blocking agent. In these patients, TNF-α blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician's global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life.
  
  
  CONCLUSIONS
  Three years of TNF-α blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-α blocking therapy in AS, in addition to the currently used more subjective measures.
authors.affiliation: Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, P,O, Box 30,001, 9700 RB Groningen, The Netherlands. s.arends@umcg.nl
authors.forename: Suzanne
authors.initials: S
authors.lastname: Arends
authors.forename: Anneke
authors.initials: A
authors.lastname: Spoorenberg
authors.forename: Pieternella M
authors.initials: PM
authors.lastname: Houtman
authors.forename: Martha K
authors.initials: MK
authors.lastname: Leijsma
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bos
authors.forename: Cees Gm
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Henk
authors.initials: H
authors.lastname: Groen
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.forename: Eveline
authors.initials: E
authors.lastname: van der Veer
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013167:Spondylitis, Ankylosing / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab