Assessment by MRI of inflammation and damage in rheumatoid arthritis patients with methotrexate inadequate response receiving golimumab: results of the GO-FORWARD trial

Abstract

Objective: To evaluate golimumab's effect on MRI-detected inflammation and structural damage in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX).

Methods: Patients (n=444) were randomly assigned to placebo plus MTX, golimumab 100 mg plus placebo, golimumab 50 mg plus MTX, or golimumab 100 mg plus MTX (subcutaneous injections every 4 weeks). A subset of 240 patients participated in an MRI substudy. MRIs (1.5T+contrast enhancement) of the dominant wrist and metacarpophalangeal (MCP) joints were obtained at baseline and weeks 12 and 24. Images were scored by two independent, blinded readers for synovitis (0-9 wrist only (n=240), 0-21 wrist+MCP (n=223)), bone oedema (osteitis) (0-69) and bone erosions (0-230) using the OMERACT Rheumatoid Arthritis MRI Scoring system.

Results: Significant improvements in synovitis and bone oedema (osteitis) were observed in the combined golimumab plus MTX groups versus placebo plus MTX at week 12 (-1.77 vs -0.15, p<0.001 wrist+MCP and -2.00 vs 0.19, p=0.003, respectively) and week 24 (-1.91 vs -0.38, p<0.001 wrist+MCP and -1.74 vs 0.71, p=0.004, respectively). Fewer than 10% of patients had a substantial degree of erosive progression (most showed no progression) across all treatment groups (including the control group), precluding adequate evaluation of golimumab's effect on bone erosions.

Conclusion: Golimumab plus MTX significantly improved MRI-detected synovitis and osteitis (prognosticators of future structural damage) versus placebo plus MTX at weeks 12 and 24. The effect of golimumab on bone erosions could not be determined by semi-quantitative scoring in these RA patients with minimal progression of bone erosions.

Figure 1

Patient disposition in the GO-FORWARD MRI substudy. MTX, methotrexate.

Figure 2

Changes from baseline to weeks 12 and 24 in synovitis (wrist plus metacarpophalangeal (MCP) joints (A), bone oedema (osteitis) (B) and bone erosion (C)). Each graph shows the mean (solid horizontal line), median (dotted horizontal line) and IQR (grey bars) for changes from baseline for each treatment group. P values are for the comparison of each golimumab treatment group with placebo using analysis of variance on the van der Waerden normal scores, with *, ** and *** indicating p<0.05, <0.01 and <0.001, respectively. GLM, golimumab; MTX, methotrexate; PBO, placebo; RAMRIS, OMERACT Rheumatoid Arthritis MRI Score.

Figure 3

MRI of the wrist at baseline (A, D, G), week 12 (B, E, H) and week 24 (C, F, I) of a patient randomised to receive golimumab 100 mg plus placebo. Coronal short tau inversion recovery (STIR) images (A–C) show extensive bone oedema at baseline (A). The bone oedema has markedly decreased at week 12 (B) and has nearly resolved at week 24 (C). Corresponding postcontrast T1-weighted images with fat suppression (D–F) show substantial synovitis at baseline (D) and markedly reduced synovitis at week 12 (E) and week 24 (F). Precontrast T1-weighted images without fat suppression (G–I) show no progression of bone erosion during the 24-week follow-up period. Note: Series of consecutive images were evaluated; the images displayed here are representative but not exhaustive.