title: Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis.
abstract: BACKGROUND
  Clinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis.
  
  
  METHODS
  The Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2-8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints.
  
  
  RESULTS
  JE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage.
  
  
  CONCLUSIONS
  Existing JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00195663. Registered 13 September 2005.
authors.affiliation: Amsterdam Rheumatology Center, Amsterdam, The Netherlands and Atrium Medical Center, Heerlen, The Netherlands. Landewe@rlandewe.nl.
authors.forename: Robert
authors.initials: R
authors.lastname: Landewé
authors.affiliation: Medical University of Vienna, Vienna, Austria. josef.smolen@wienkav.at.
authors.forename: Josef S
authors.initials: JS
authors.lastname: Smolen
authors.affiliation: AbbVie, Rungis, France. stefan.florentinus@abbvie.com.
authors.forename: Stefan
authors.initials: S
authors.lastname: Florentinus
authors.affiliation: AbbVie Inc., North Chicago, IL, USA. su.chen@abbvie.com.
authors.forename: Su
authors.initials: S
authors.lastname: Chen
authors.affiliation: AbbVie Inc., North Chicago, IL, USA. benoit.guerette@abbvie.com.
authors.forename: Benoît
authors.initials: B
authors.lastname: Guérette
authors.affiliation: Leiden University Medical Center, Leiden, The Netherlands. mail@dvanderheijde.nl.
authors.forename: Désirée
authors.initials: D
authors.lastname: van der Heijde
mesh_terms: D000068879:Adalimumab / Q000008:administration & dosage; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011859:Radiography; D013585:Synovitis / Q000000981:diagnostic imaging*
chemical_list: D018501:Antirheumatic Agents; D000068879:Adalimumab; D008727:Methotrexate