Response of ultrasound-assessed synovitis to baricitinib, in monotherapy and combined with methotrexate, compared with etanercept in rheumatoid arthritis: a randomised, international, multicentre trial.

Abstract

The primary objective of this randomised, active-controlled, international, multicentre, phase IV clinical trial was to demonstrate noninferiority of the response of ultrasound-assessed synovitis to baricitinib treatment, alone and in combination with methotrexate (MTX), compared with etanercept with MTX in rheumatoid arthritis (RA). Adult patients with active RA and inadequate response to MTX were randomised into 3 parallel treatment groups: baricitinib monotherapy, baricitinib plus MTX, and etanercept plus MTX. The patients underwent clinical, ultrasound, and laboratory assessments at baseline, 4, 12, and 24 weeks. Ultrasound synovitis was scored 0 to 3 in B-mode, Doppler mode, and a combination of both modes. The primary endpoint was the change in the Global European Alliance of Associations for Rheumatology-Outcome Measures in Rheumatology Synovitis Score (GLOESS) for bilateral wrist and metacarpophalangeal joints at week 12. Noninferiority was stated if the changes in the baricitinib groups were above the lower limit of the noninferiority range, defined as 80% of changes observed in the etanercept plus MTX group. Changes in serum concentrations of different mediators were analysed at 24 weeks. One hundred fifty patients (109 women and 41 men) were randomised. All clinical and ultrasound variables showed significant improvement starting from week 4 across the 3 treatment arms (P < .050). Noninferiority of baricitinib (monotherapy and plus MTX) was confirmed against etanercept with MTX for GLOESS at week 12 (P < .050). Changes in metalloprotease-3 concentration significantly correlated with changes in all ultrasound scores. The response of ultrasound-assessed synovitis to baricitinib, alone or in combination with MTX, was noninferior to that of etanercept with MTX.