title: Meta-analysis of long-term joint structural deterioration in minimally treated patients with rheumatoid arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint structural deterioration. Driven by recent expectations that patients in clinical trials randomized to placebo should be 'rescued' with active therapy within 6 months of starting treatment, the relative benefit of arresting joint damage with biologic agents beyond this period is unclear. With longer-term evidence of the rate of joint deterioration with minimal treatment, the efficacy of biologic agents and novel treatments might be projected beyond the placebo-controlled phase observed in clinical trials. The aim of this study was to estimate radiographic structural deterioration over time in patients with moderate-to-severe RA minimally treated with DMARDs.
  
  
  
  A literature review identified evidence of joint structural deterioration in patients with (DMARD-IR population) and without (non-DMARD-IR population) a history of inadequate response to DMARDs. Patients were minimally treated with one non-biologic DMARD or palliative care (non-DMARD-IR population only). Outcomes of interest were the (modified) Total Sharp Score (TSS) and subscales (Erosion Subscore [ES] and Joint Space Narrowing [JSN] Subscore), and Larsen score. Pooled joint-deterioration curves over time were obtained with meta-analysis models.
  
  
  
  Mean change from baseline in TSS increased in the DMARD-IR population from 1.14 (95 % credible interval [CrI] 0.66, 1.67) to 9.84 (5.68, 14.46) at Weeks 12 and 104, respectively, and a non-linear increase of 1.56 (0.79, 2.34) and 5.13 (-1.35, 11.67) in the non-DMARD-IR population. At the same time points, mean changes (95 % CrI) were 0.51 (0.27, 0.83) and 4.43 (2.38, 7.21) for ES and 0.36 (0.09, 0.67) and 3.14 (0.80, 5.78) for JSN in the DMARD-IR population, whereas corresponding changes in the non-DMARD-IR population were 0.69 (0.31, 1.12) and 2.93 (0.92, 5.02), and 0.29 (0.17, 0.44) and 2.55 (1.45, 3.80), respectively. Larsen scores were only available for the non-DMARD-IR population, with mean changes (95 % CrI) of 0.08 (0.04, 0.11) and 0.65 (0.36, 0.96) at Weeks 12 and 104, respectively.
  
  
  
  Minimal treatment of RA with one non-biologic DMARD results in deterioration of joint structure in patients with or without a history of inadequate response to non-biologic DMARDs.
authors.affiliation: Tufts University School of Medicine, Boston, MA, USA. jeroen.jansen@tufts.edu.|, 1714 Stockton Street, 3rd floor, San Francisco, CA, 94133, USA. jeroen.jansen@tufts.edu.
authors.forename: Jeroen P
authors.initials: JP
authors.lastname: Jansen
authors.affiliation: Formerly at Mapi, Boston, MA, USA.
authors.forename: Maria-Cecilia
authors.initials: MC
authors.lastname: Vieira
authors.affiliation: Pfizer Medicines Development Group, Groton, CT, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Bradley
authors.affiliation: Pfizer Medicines Development Group, Groton, CT, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Cappelleri
authors.affiliation: Pfizer Medicines Development Group, Groton, CT, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Zwillich
authors.affiliation: Pfizer Medicines Development Group, Groton, CT, USA.
authors.forename: Gene V
authors.initials: GV
authors.lastname: Wallenstein
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D007596:Joints / Q000473:pathology*; D017211:Treatment Failure
chemical_list: D018501:Antirheumatic Agents
keywords: Joint erosions; Longitudinal studies; Meta-analysis; Radiography; Rheumatoid arthritis