Dataset Information

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.

SUBMITTER: Conaghan PG

PROVIDER: S-EPMC3995246 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Publications

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

Conaghan Philip G PG Peterfy Charles C Olech Ewa E Kaine Jeffrey J Ridley David D Dicarlo Julie J Friedman Josh J Devenport Jenny J Troum Orrin O

Annals of the rheumatic diseases 20140213 5

<h4>Objective</h4>To examine the imaging-detected mechanism of reduction of structural joint damage progression by tocilizumab (TCZ) in patients with rheumatoid arthritis (RA) using MRI.<h4>Methods</h4>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 additi ...[more]

PMID: 24525910

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Project description:Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1?, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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