Limited Advantage to Very Early vs. Delayed Etanercept in RA Save

The VEDERA study sought to confirm whether the very early introduction of first-line etanercept+methotrexate (ETN+MTX) was superior to treat-to-target MTX (MTX-TT) in patients with early RA.

The study enrolled 120  treatment-naïve seropositive ERA (≤12 months symptom) patients with active disease (DAS28-ESR ≥3.2) and studied by clinical measures or ultrasound power Doppler (PD). Subjects receiving MTX-TT, were escalated to ETN if week 24 DAS28-ESR ≥2.6. The primary endpoint DAS28ESR remission was assessed at week 48.

The group was 71% female, 73% RF/84% ACPA positive, with a median symptom duration 20.3 and basedline DAS28 of 5.1 (1.1)).

Remission rates were:

Week 24                 Week 48

• ETN+MTX= 38%                     52%
• MTX-TT  = 33%                      38%    (ORs 1.6, 95% CI 0.8 to 3.5, p=0.211).

Sustained DAS28-ESR remission more likely with ETN+MTX versus MTX-TT (42% and 27%; p=0.035).

If ETN administered first line, there was an almost 3-fold increase odds (OR 2.84) of achieving remission, compared to starting ETN after 24 weeks of just MTX therapy.

While previous studies suggested that very early introduction of TNFI+MTX would have a larger beneficial effect, these studies failed to prove this contention, although giving ETN after failure of MTX-TT did yield lesser responses.