A 6-Months Infliximab Or Placebo Study In UA At High Risk Of RA:Clinical,Radiological And Synovial Benefit (UA-IFX)

• To test the hypothesis that induction therapy with infliximab is followed by a better clinical outcome over a 2 year follow-up and defined as a lower rate of patients with ACR criteria at 6, 12 and 24 months. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  no necessary
• To assess the effects of infliximab on synovial histopathology of UA. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  no necessary
• To test the hypothesis that infliximab can influence the presence of anti CCP antibodies. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  no necessary
• To assess physical function and health-related quality of life using the Disability Index of HAQ (HAQ) and SF-36 instruments, respectively [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  no necessary

Patient with undifferentiated arthritis and the presence of anti-CCP antibodies are at high risk to develop RA. The presence of anti-CCP is associated with a higher rate of erosion and a higher risk of progressive and severe RA.

The investigators have demonstrated in the CIERA study that MTX/IFX combination therapy is superior to MTX alone to reduce MRI signs of synovitis and bone edema and is clinically more effective.

The immunopathogenesis of undifferentiated arthritis is poorly understood. However, synovial studies from patients with early arthritis suggest that UA and RA may share common immunopathogenic mechanisms. One biopsy study of asymptomatic joints in patients with early arthritis demonstrates synovitis in more than half of the joints samples with prominent T cell and macrophage infiltration, similar to RA.

Thus intensive treatment with anti-TNF antibodies (infliximab) may have an impact on multiple immune mechanisms driving synovitis in undifferentiated arthritis and may influence the clinical outcome.

Recently, Methotrexate has been demonstrated to improve the course of undifferentiated arthritis and prevent the development of RA. Short regimen of more intensive therapy with Infliximab could alter the radiological, immunopathological and clinical outcome.

not necessary

• Drug: Infliximab
  Infliximab 3 mg/kg wk 0,2,6
  Other Name: FR-BR7794
• Drug: sodium chloride
  Group II : Placebo wk 0,2,6
  Other Name: not available

• Experimental: Infliximab
  Group I: Infliximab 3 mg/kg wk 0,2,6
  Intervention: Drug: Infliximab
• Placebo Comparator: sodium chloride
  PR1 solution for infusion, intravenous use Sterile normal saline 0.9% sodium chloride
  Intervention: Drug: sodium chloride

Inclusion Criteria:

Diagnosis of UA Absence of ACR criteria Active UA defined by a swollen joint count ≥ 1 and < 4 Positive anti-CCP Disease duration < 2 years DMARDs naive No chronic treatment with steroids (> 3 months), if needed washout of 4 weeks NSAIDs stable

Exclusion Criteria:

Other rheumatic inflammatory diagnosis Contraindication to MRI (pace-maker, etc.) Congestive heart disease Active or latent tuberculosis