title: Predictors for the progression of cervical lesion in rheumatoid arthritis under the treatment of biological agents.
abstract: METHODS
  Retrospective cohort analysis.
  
  
  OBJECTIVE
  To clarify the effect of biological agents (BAs) on the development and progression of cervical lesions in patients with rheumatoid arthritis (RA) and to identify biomarkers that accurately predict disease progression.
  
  
  BACKGROUND
  The introduction of BAs changed the paradigm of RA treatment. However, their effects on cervical lesions in patients with RA have not been studied.
  
  
  METHODS
  Ninety-one subjects who had received BAs for 2 years or more were enrolled. Mean radiographical interval was 3.9 years. Disease activity was evaluated by disease activity score-C-reactive protein levels, and matrix metalloproteinase-3 levels. Cervical lesions were defined as an atlantodental interval more than 3 mm for atlantoaxial subluxation (AAS), Ranawat value less than 13 mm for vertical subluxation (VS), and anterior or posterior listhesis more than 2 mm for subaxial subluxation. Disease progression was defined radiographically as an increase in the atlantodental interval more than 2 mm for AAS, a decrease in both Ranawat and Redlund-Johnell values more than 2 mm for VS, and an increase in listhesis more than 2 mm for subaxial subluxation. We used multivariate regression techniques to assess predictors of disease progression.
  
  
  RESULTS
  Baseline radiographical evaluation showed no pre-existing cervical lesion in 44 patients, AAS in 29, and VS in 18. Radiological progression occurred in 7% patients without baseline lesions, 79% in the AAS group, and 72% in the VS group. The incidence of progression was significantly lower in patients without lesions at baseline. Multivariate regression analysis demonstrated pre-existing cervical lesions, disease activity score-C-reactive protein levels at baseline and metalloproteinase-3 levels at final visit as good predictors of RA progression.
  
  
  CONCLUSIONS
  BAs prevented de novo cervical lesions in patients with RA but failed to control progression in patients with pre-existing cervical lesions. Disease activity score-C-reactive protein levels at baseline were related to pre-existing joint destruction, and metalloproteinase-3 levels accurately predicted ongoing bone destruction during BA treatment.
  
  
  METHODS
  3.
authors.affiliation: *Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan; Departments of †Rheumatology; and ‡Orthopaedic Surgery, National Hospital Organization Osaka Minami Medical Center, Osaka, Japan; and §Graduate School of Health Care Sciences, Jikei Institute, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kaito
authors.forename: Shirou
authors.initials: S
authors.lastname: Ohshima
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Takahiro
authors.initials: T
authors.lastname: Makino
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yonenobu
mesh_terms: D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D001268:Atlanto-Axial Joint / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D001685:Biological Factors / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism; D002574:Cervical Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D004204:Joint Dislocations / Q000188:drug therapy; D007593:Joint Instability / Q000188:drug therapy; D016015:Logistic Models; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011859:Radiography; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D001685:Biological Factors; D015415:Biomarkers; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3