Objectives: We sought to confirm in very early rheumatoid arthritis (ERA) a much greater superiority (30%) of first-line etanercept+methotrexate (ETN+MTX) over treat-to-target MTX (MTX-TT) than previously reported in ERA (14%); and explore whether ETN following initial MTX secures a comparable response to first-line ETN+MTX.
Methods: Pragmatic, open-label, RCT of treatment-naïve ERA (≤12 month symptom), DAS28ESR≥3.2, rheumatoid factor(RF) +/- anti-citrullinated peptide antibody(ACPA) positive, or ultrasound power Doppler(PD) if RF and ACPA negative. Subjects were randomised 1:1 to ETN+MTX; or MTX-TT, escalated to ETN if week 24 DAS28-ESR≥2.6; and intramuscular corticosteroid at protocolised timepoints. Primary endpoint of week 48 DAS28ESR remission with clinical and imaging secondary endpoints.
We randomised 120 patients, 60 to each arm [71% female, 73% RF/84% ACPA positive, median (IQR) symptom duration 20.3(13.1, 30.8) weeks; mean(SD) DAS28 5.1(1.1)]. Remission rates with ETN+MTX and MTX-TT respectively were 38% vs 33% at week 24; 52% vs 38% at week 48 [odds ratio (OR)(95% CI)=1.6(0.8, 3.5), p=0.211]. Greater, sustained DAS28-ESR remission observed with ETN+MTX vs MTX-TT (42% and 27% respectively; p=0.035). PD was fully suppressed by week 48 in over 90% in each arm. Planned exploratory analysis revealed OR(95% CI) 2.84(0.8, 9.6) of achieving remission after 24 weeks of ETN administered first-line compared to administered post-MTX.
Conclusions: Compared to remission rates typically reported with first-line TNFi+MTX versus MTX-TT, we did not demonstrate a larger effect in very ERA. Neither strategy conferred remission in the majority of patients although ultrasound confirmed local inflammation suppression. Poorer ETN response following failure of MTX-TT is also suggested.