The effects of tocilizumab on osteitis, synovitis and erosion progression in rheumatoid arthritis: results from the ACT-RAY MRI substudy

Abstract

Objective: To examine the imaging-detected mechanism of reduction of structural joint damage progression by tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) using MRI.

Methods: In a substudy of a randomised, double-blind, phase 3b study (ACT-RAY) of biologic-naïve patients with RA who were methotrexate (MTX)-inadequate responders, 63 patients were randomised to continue MTX or receive placebo (PBO), both in combination with TCZ 8 mg/kg every 4 weeks, with optional additional disease-modifying antirheumatic drugs at week 24 if Disease Activity Score of 28 joints < 3.2. The most symptomatic hand was imaged with 0.2 Tesla extremity MRI at weeks 0, 2, 12 and 52. MR images were scored using Outcome Measures in Rheumatology-Rheumatoid Arthritis Magnetic Resonance Imaging Score. Predictors of week 52 erosion progression were determined by logistic regression analysis.

Results: TCZ + PBO (n=32) demonstrated mean improvements in synovitis from baseline to weeks 2 (-0.92; p=0.0011), 12 (-1.86; p<0.0001) and 52 (-3.35; p<0.0001), while TCZ + MTX (n=31) had mean improvements in synovitis at week 12 (-0.88; p=0.0074), but not week 52 (-1.00; p=0.0711). TCZ+PBO demonstrated mean reductions in osteitis at weeks 12 (-5.10; p=0.0022) and 52 (-8.56; p=0.0006), while TCZ+MTX had mean reductions at weeks 2 (-0.21; p<0.05) and 12 (-3.63; p=0.0008), but not week 52 (-2.31; p=0.9749). Mean erosion scores did not worsen in either group. MRI erosion scores at weeks 12 and 52 correlated strongly with radiography erosion scores at week 52 (r>0.80). Baseline synovitis and worsening of osteitis predicted erosion progression.

Conclusions: Rapid suppression of synovitis and osteitis with reduction in structural joint damage progression occurred with TCZ, as monotherapy or in combination with MTX, through week 52.

Keywords: DMARDs (biologic); Disease Activity; Magnetic Resonance Imaging; Rheumatoid Arthritis; Synovitis.

Figure 1

Patient disposition. DMARD, disease-modifying antirheumatic drug; mITT, modified intent-to-treat; MTX, methotrexate; PBO, placebo; TCZ, tocilizumab.

Figure 2

Changes in MRI scores in patients taking tocilizumab (TCZ) 8 mg/kg plus methotrexate (MTX) or placebo (PBO) plus MTX. (A) Mean change from baseline in synovitis scores over 52 weeks and cumulative distribution plot of the mean change from baseline in synovitis scores at week 52. (B) Mean change from baseline in osteitis scores over 52 weeks and cumulative distribution plot of the mean change from baseline in osteitis scores at week 52. (C) Mean change from baseline in erosion scores over 52 weeks and cumulative distribution plot of the mean change from baseline in erosion scores at week 52. Synovitis scores could range from 0 to 24. Osteitis scores could range from 0 to 75. Erosions scores could range from 0 to 250. p Value is from the within-group Wilcoxon signed-rank test of the hypothesis of no change from baseline. SDC, smallest detectable change.

Figure 3

Correlation between radiographic erosion scores at 52 weeks and MRI erosion scores at weeks 12 and 52. MTX, methotrexate; PBO, placebo; TCZ, tocilizumab.

Figure 4

Disease Activity Score using 28 joints over 52 weeks. MTX, methotrexate; PBO, placebo; TCZ, tocilizumab.