Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Infliximab Versus Placebo in Adult Patients with ACPA Positive Undifferentiated Arthritis.
Durez1, Patrick, de Bellefon1, Laurent Meric, Depresseux1, Genevieve, Toukap1, Adrien Nzeusseu, Lauwerys1, Bernard, Houssiau2, Frédéric. A.
Patients (pts) with Undifferentiated Arthritis (UA), positive for ACPA antibodies are at high risk of progressing to Rheumatoid Arthritis (RA). TNF plays a key role in the pathogenesis of RA. Very early treatment with the combination of Methotrexate and Infliximab (IFX) in a small cohort of UA showed a benefit in clinical symptoms and reduction of MRI evidence of synovitis and erosions1.
To assess whether IFX is more effective than placebo (Pbo) in preventing the development of RA in adult pts with UA at high risk of the development of RA. Other end points were clinical response and synovitis assessed by MRI and synovial biopsy.
This was a randomized, double-blind, Pbo-controlled, two-arm parallel design study of 12 months to the primary endpoint (proportion of pts who developed RA by ARA 2007 criteria). Pts with UA and symptomatic clinical synovitis of >=1 joints and ACPA positivity were randomized 1:1 to IFX (3 mg/kg) or Pbo at week 0, 2, 6, 14 and 22, after which treatment was terminated. NSAIDs/stable low-dose oral corticosteroid (<=5 mg/day prednisone or equivalent) were permitted but no DMARDs. Pts who developed RA at any time were discontinued and could receive standard of care. Paired synovial biopsies were harvested by needle-arthroscopy at baseline and at week 12 from the knee of 8 Pbo and 8 IFX patients.
30 pts were randomized (mean age: 48 +/- 12 yrs; mean duration of arthritis: 0.34 +/- 0.53 yr; mean CRP level: 1.67 +/- 2.23 mg/dL); 7 had preexisting erosions. By 1 yr, 11/15 pts treated with IFX developed RA vs 10/15 Pbo-treated pts (Kaplan Meier, log rank p=0.868). At week 14, peak ACR 20, 50, 70 responses were observed respectively in 71.4%, 42.9%, 28.6% pts treated with IFX vs 21.4%, 0%, 0% treated with Pbo. Remission DAS28CRP rate was observed in 50% in the IFX group vs 21.4% in the Pbo group. Pbo and IFX did not display any differential effect on semi-quantitative evaluation of synovial CD3, CD15, CD20, CD68 and CD138 positive cells between baseline and week 12.
No severe safety issue was observed except one case of severe hepatotoxicity induced by Isoniazid.
IFX is effective in ACPA positive UA patients but did not prevent the progression to definite RA. In a majority of these patients, longterm DMARDs therapy is indicated.
To cite this abstract, please use the following information:
Durez, Patrick, de Bellefon, Laurent Meric, Depresseux, Genevieve, Toukap, Adrien Nzeusseu, Lauwerys, Bernard, Houssiau, Frédéric. A.; Infliximab Versus Placebo in Adult Patients with ACPA Positive Undifferentiated Arthritis. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :435