title: Baseline predictors of response and discontinuation of tumor necrosis factor-alpha blocking therapy in ankylosing spondylitis: a prospective longitudinal observational cohort study.
abstract: BACKGROUND
  Identifying ankylosing spondylitis (AS) patients who are likely to benefit from tumor necrosis factor-alpha (TNF-α) blocking therapy is important, especially in view of the costs and potential side effects of these agents. Recently, the AS Disease Activity Score (ASDAS) has been developed to assess both subjective and objective aspects of AS disease activity. However, data about the predictive value of the ASDAS with respect to clinical response to TNF-α blocking therapy are lacking. The aim of the present study was to identify baseline predictors of response and discontinuation of TNF-α blocking therapy in AS patients in daily clinical practice.
  
  
  METHODS
  AS outpatients who started TNF-α blocking therapy were included in the Groningen Leeuwarden Ankylosing Spondylitis (GLAS) study, an ongoing prospective longitudinal observational cohort study with follow-up visits according to a fixed protocol. For the present analysis, patients were excluded if they had previously received anti-TNF-α treatment. Predictor analyses of response and treatment discontinuation were performed using logistic and Cox regression models, respectively.
  
  
  RESULTS
  Between November 2004 and April 2010, 220 patients started treatment with infliximab (n = 32), etanercept (n = 137), or adalimumab (n = 51). At three and six months, 68% and 63% of patients were Assessments in Ankylosing Spondylitis (ASAS)20 responders, 49% and 46% ASAS40 responders, and 49% and 50% Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)50 responders, respectively. Baseline predictors of response were younger age, male gender, higher ASDAS score, higher erythrocyte sedimentation rate (ESR) level, higher C-reactive protein (CRP) level, presence of peripheral arthritis, higher patient's global assessment of disease activity, and lower modified Schober test. In August 2010, 64% of patients were still using their TNF-α blocking agent with a median follow-up of 33.1 months (range 2.4 to 68.2). Baseline predictors of discontinuation of TNF-α blocking therapy were female gender, absence of peripheral arthritis, higher BASDAI, lower ESR level, and lower CRP level.
  
  
  CONCLUSIONS
  Besides younger age and male gender, objective variables such as higher inflammatory markers or ASDAS score were identified as independent baseline predictors of response and/or continuation of TNF-α blocking therapy. In contrast, higher baseline BASDAI score was independently associated with treatment discontinuation. Based on these results, it seems clinically relevant to include more objective variables in the evaluation of anti-TNF-α treatment.
authors.affiliation: Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. S.Arends@reuma.umcg.nl
authors.forename: Suzanne
authors.initials: S
authors.lastname: Arends
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Brouwer
authors.forename: Eveline
authors.initials: E
authors.lastname: van der Veer
authors.forename: Henk
authors.initials: H
authors.lastname: Groen
authors.forename: Martha K
authors.initials: MK
authors.lastname: Leijsma
authors.forename: Pieternella M
authors.initials: PM
authors.lastname: Houtman
authors.forename: Tim L
authors.initials: TL
authors.lastname: Th A Jansen
authors.forename: Cees G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: Anneke
authors.initials: A
authors.lastname: Spoorenberg
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects; D000069285:Infliximab; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D012720:Severity of Illness Index; D013167:Spondylitis, Ankylosing / Q000188:drug therapy*; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept