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

Abstract

ObjectiveTo examine the imaging-detected mechanism of reduction of structural joint damage progression by tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) using MRI.MethodsIn 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.ResultsTCZ + 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.ConclusionsRapid 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.

Assessment of Inflammation and Damage in Rheumatoid Arthritis Patients with Methotrexate Inadequate Response Receiving Tocilizumab Using Low Field MRI

“…The same results were found in the study of P. G Conaghan et al [7] in patients with RA treated with Golimumab plus MTX significantly improved MRIdetected synovitis and osteitis at weeks 12 and 24, and in the study of Suzuki et al [6] in patients with RA treated with tocilizumab at 44 weeks but not at 20 weeks. Recently, Conaghan PG et al [38] had found a 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. However, in 2 others studies, there was an improvement of the RAMRIS erosions score, while the modification of RAMRIS synovitis and RAMRIS oedema scores remain trivial.…”

Efficacy of tocilizumab on MRI-determined bone oedema in rheumatoid arthritis

“…Treatment of patients with TCZ also inhibited progression of radiographic joint damage as measured by X-ray within 6 months of treatment initiation. However, there are limited data on the tissue-level effects of TCZ [2].…”

“…The efficacy and safety of TCZ monotherapy and TCZ in combination with disease-modifying anti-rheumatic drugs were shown in adult patients with RA in five pivotal phase 3 clinical trials [2]. Treatment of patients with TCZ also inhibited progression of radiographic joint damage as measured by X-ray within 6 months of treatment initiation.…”

“…Conventional radiographs (CRs) have traditionally been used to detect structural damage, signs of bone erosion and joint space narrowing in rheumatoid arthritis. Magnetic resonance imaging (MRI)-a more sensitive and specific technique than clinical examination or plain film radiography-can measure inflammation in the synovium (synovitis) and bone marrow (osteitis) as well as structural damage [2]. MRI bone oedema is a strong independent predictor of subsequent radiographic progression in early RA and should be considered for use as a prognostic indicator.…”

“…Both synovitis and osteitis play a central role in the pathogenesis of RA and predict radiographic progression [2]. Conventional radiographs (CRs) have traditionally been used to detect structural damage, signs of bone erosion and joint space narrowing in rheumatoid arthritis.…”