Clinical and economic burden of extra-articular manifestations in ankylosing spondylitis patients treated with anti-tumor necrosis factor agents

J Med Econ. 2012;15(6):1054-63. doi: 10.3111/13696998.2012.692341. Epub 2012 Jun 11.


Objective: To assess concomitant extra-articular manifestation (EAM) rates in patients with ankylosing spondylitis (AS) treated with anti-tumor necrosis factor (anti-TNF) agents and examine the economic burden of uveitis and inflammatory bowel disease (IBD) in French and German AS patients.

Methods: Previous analyses of uveitis and IBD in AS patients treated with infliximab, etanercept or adalimumab were identified in PubMed/Medline (January 2000 to August 2011). A supplemental analysis incorporated more recent adalimumab clinical trial data (ATLAS [NCT00085644] and RHAPSODY [NCT00478660]). For resource utilization/costs associated with EAMs, the search was expanded to general spondyloarthritis (SpA) conditions (i.e., AS, reactive or psoriatic arthritis, psoriatic spondylitis, IBD and undifferentiated SpA). Direct and indirect yearly costs associated with AS-associated uveitis and IBD were estimated based on interviews with French and German clinicians and literature review.

Results: The pooled average rate of anterior uveitis (AU) flares for patients treated with anti-TNF therapy in two meta-analyses and supplemental adalimumab clinical trials was 4.9/100-patient-years (PYs). AU rates (per 100-PYs) were 3.4, 3.7 and 5.7 for infliximab (p=0.26 vs etanercept; p=0.86 vs adalimumab), adalimumab (p=0.033 vs etanercept) and etanercept, respectively. IBD flares (per 100-PYs) were 0.2 for infliximab (p<0.001 vs etanercept; p=0.18 vs adalimumab), 0.63 for adalimumab (p=0.009 vs etanercept) and 2.2 for etanercept. No studies assessing EAM-associated resource utilization or costs in AS patients were found. Direct medical costs associated with IBD treatment ranged from €483 (Germany) to €6443 (France). Clinician-estimated AS-related uveitis direct medical costs were €1410 (Germany) and €1812 (France).

Conclusions: Clinical data synthesis demonstrated significantly lower AU flare rates with adalimumab vs etanercept and significantly lower IBD rates with both adalimumab and infliximab vs etanercept. Economic analysis indicated substantial costs associated with AU and IBD flares secondary to AS in France and Germany. Future economic evaluations of anti-TNF agents should incorporate EAMs and subsequent treatment costs. Limitations include restricted availability of randomized, placebo-controlled clinical trial data, inclusion of data from open-label studies, lack of real-world (i.e., non-trial-based) EAM rates and a lack of EAM-specific direct and indirect costs with which to compare the results presented herein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab
  • Antibodies, Monoclonal / economics
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / economics
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antirheumatic Agents / economics*
  • Antirheumatic Agents / therapeutic use*
  • Etanercept
  • France
  • Germany
  • Health Services / economics
  • Health Services / statistics & numerical data
  • Humans
  • Immunoglobulin G / economics
  • Immunoglobulin G / therapeutic use
  • Inflammatory Bowel Diseases / economics
  • Inflammatory Bowel Diseases / etiology
  • Infliximab
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Retrospective Studies
  • Spondylarthritis / complications*
  • Spondylarthritis / drug therapy*
  • Spondylitis, Ankylosing / complications
  • Spondylitis, Ankylosing / drug therapy
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Uveitis, Anterior / economics
  • Uveitis, Anterior / etiology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Infliximab
  • Adalimumab
  • Etanercept