OP-0130 – Efficacy of Abatacept in Delaying the Development of Rheumatoid Arthritis (RA) in Adult Patients with Undifferentiated Inflammatory Arthritis (UA) at High Risk of Developing RA.
Emery, Durez, Dougados, Becker, Vratsanos, Mitra, Overfield, Qi, Westhovens. UK, Belgium, France, US. [Sponsor, BMS]
Objective:
To assess whether abatacept is more effective than placebo in preventing the development of RA in anti-CCP positive adult pts with UA who are at high risk of developing RA.
Methods:
This was a randomized, double-blind, Phase II, placebo-controlled, two-arm parallel-design, exploratory study. The primary outcome was the proportion of patients who developed RA by ACR criteria at 12 months. The secondary outcomes were structural (MRI and xray changes) at 24 months.
Pts with UA and ≥2 swollen joints and anti-CCP2 positivity were randomized 1:1 to abatacept (∼10 mg/kg) or placebo for up to 6 months, after which treatment was terminated. NSAIDs and stable low-dose prednisone (≤10 mg/day or equivalent) were permitted but no DMARDs. Pts who developed RA at any time were discontinued and could receive standard of care.
Results:
50 of 56 randomized pts were evaluable. For the 56 randomized pts, mean age was 45 yrs; mean duration of symptoms 8 months [range 1–18 mths]; mean CRP level was 1.1 mg/dL; 78.6% had oligoarthritis, 55.4% had erosions. By 12 months, 12/26 (46%) pts treated with abatacept developed RA vs 16/24 (67%) of placebo-treated pts (20.5% difference; 95% confidence interval –7.8 to +47.4). The total Sharp score for the abatacept treated group at 12 months was 0.02 while that for the placebo group was 1.11 (difference of -1.10 (95% CI -2.03, -0.17).
Conclusion:
Abatacept may delay progression to definite RA in some pts with UA.
Editorial Comment:
This was essentially a negative study. The difference in progression rates to RA in the abatacept and placebo groups was not statistically significant. The question, however, is whether the study was powered so as to be able to detect such a difference were one to actually exist. Insofar as T cells are presumed to be important early players in the pathogenesis of RA, and abatacept is a T cell inhibitor (of costimulation) and is effective advanced RA, one might have expected it to be more efficacious in slowing progress of undifferentiated inflammatory arthritis to full fledged RA.
