title: Effectiveness and Drug Survival of TNF Inhibitors in the Treatment of Ankylosing Spondylitis: A Prospective Cohort Study.
abstract: OBJECTIVE
  The aim of this research was to describe the effectiveness and drug survival of tumor necrosis factor (TNF) inhibitors in the treatment of ankylosing spondylitis (AS) and to analyze the effect of concomitant treatment with conventional disease-modifying antirheumatic drugs.
  
  
  METHODS
  Patients with AS identified from the National Register for Biologic Treatment in Finland starting their first TNF inhibitor treatment between July 2004 and December 2011 were included. Treatment response was measured as an improvement of 50% (or 20 mm) after 6 months of treatment onset compared to the baseline Bath AS Disease Activity Index (BASDAI) score. Treatment response and 2-year drug survival were modeled with logistic regression and time-dependent Cox proportional hazard models, respectively.
  
  
  RESULTS
  The study comprised 543 patients, of whom 123 also commenced a second TNF inhibitor during the followup. Treatment was discontinued within 24 months by 25% and 28% of the users of the first and the second TNF inhibitors, respectively. BASDAI response at 6 months was achieved by 52% and 25% of the users of the first and the second TNF inhibitors, respectively. Etanercept (ETN; HR 0.42, 95% CI 0.29-0.62) and adalimumab (ADA; HR 0.48, 95% CI 0.30-0.77) were associated with better drug survival in comparison to infliximab (IFX). Also, concurrent use of sulfasalazine (SSZ; HR 0.70, 95% CI 0.49-0.99) decreased the hazard for treatment discontinuation.
  
  
  CONCLUSIONS
  TNF inhibitors are equipotent in the treatment of AS; however, ETN and ADA were found superior to IFX in drug survival. The use of SSZ improves treatment continuation.
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital. arto.heinonen@helsinki.fi.
authors.forename: Arto V
authors.initials: AV
authors.lastname: Heinonen
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Kalle J
authors.initials: KJ
authors.lastname: Aaltonen
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Jaana T
authors.initials: JT
authors.lastname: Joensuu
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Jukka P
authors.initials: JP
authors.lastname: Lähteenmäki
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Marja I
authors.initials: MI
authors.lastname: Pertovaara
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Matti K
authors.initials: MK
authors.lastname: Romu
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Hirvonen
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Aki K
authors.initials: AK
authors.lastname: Similä
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Marja L
authors.initials: ML
authors.lastname: Blom
authors.affiliation: From the University of Helsinki, Helsinki; North Carelia Central Hospital, Joensuu; Tampere University Hospital, Tampere; Helsinki University Central Hospital, Helsinki; Turku City Hospital, Turku, Finland.A.V. Heinonen, BSc(pharm), University of Helsinki; K.J. Aaltonen, PhD (pharm), University of Helsinki; J.T. Joensuu, MSc(pharm), University of Helsinki; J.P. Lähteenmäki, MD, North Carelia Central Hospital; M.I. Pertovaara, MD, PhD, Tampere University Hospital; M.K. Romu, MD, Helsinki University Central Hospital; H.E. Hirvonen, MD, Helsinki University Central Hospital; A.K. Similä, MD, Turku City Hospital; M.L. Blom, PhD, Professor, University of Helsinki; DC Nordström, MD, PhD, Adj. Professor, University of Helsinki, and Helsinki University Central Hospital.
authors.forename: Dan C
authors.initials: DC
authors.lastname: Nordström
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D015331:Cohort Studies; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005387:Finland; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D018570:Risk Assessment; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000175:diagnosis* / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000037:antagonists & inhibitors*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha
keywords: ANKYLOSING SPONDYLITIS; ANTIRHEUMATIC AGENTS; EPIDEMIOLOGIC METHODS; SULFASALAZINE; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR-A