Pre-treatment interleukin-6 levels strongly affect bone erosion progression and repair detected by magnetic resonance imaging in rheumatoid arthritis patients

Kondo, Yasushi; Kaneko, Yuko; Sugiura, Hiroaki; Matsumoto, Shunsuke; Nishina, Naoshi; Kuwana, Masataka; Jinzaki, Masahiro; Takeuchi, Tsutomu

doi:10.1093/rheumatology/kex046

Cited by 18 publications

(12 citation statements)

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“…These data suggest that IL-6 exerts a more fundamental effect on the generation of bone erosions than TNFα. Previous data showing that baseline IL-6 serum level is associated with the progression of bone erosions in RA 20. This result is despite the fact that inhibition of IL-6R and TNFα show virtually identical effects on the control of the signs and symptoms of RA, both reaching very similar remission rates.…”

Section: Discussionmentioning

confidence: 68%

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis

et al. 2019

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ObjectiveTo compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhibition on inducing repair of existing bone erosions in patients with very early rheumatoid arthritis (RA).MethodsProspective non-randomised observational study in patients with active erosive RA with inadequate response to methotrexate (MTX) receiving either tocilizumab (TOC) monotherapy or adalimumab (ADA) with MTX for 52 weeks. Erosion volumes were assessed in metacarpal heads (MCH) and the radius by high-resolution peripheral quantitative CT at baseline and after 52 weeks. Clinical response was monitored using Clinical Disease Activity Index, Simple Disease Activity Index and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) scores every 12 weeks.ResultsTOC (N=33) and ADA/MTX (N=33) treatment groups were balanced for age, sex, body mass index, comorbidities, disease and activity, functional state, autoantibody status, baseline bone damage and baseline bone biomarkers. Both TOC (DAS28-ESR: baseline: 6.2±0.5; 52 weeks: 2.3±1.0) and ADA/MTX (6.3±0.6; 2.8±1.2) significantly reduced disease activity. Erosion volumes significantly decreased in the MCH and radius of patients with RA treated with TOC (p<0.001) but not in patients treated with ADA/MTX (p=0.77), where they remained stable in size. Mean decrease in erosion volume in TOC-treated patients was −1.0±1.1 mm3 and −3.3±5.9 mm3 in the MCH and radius of TOC-treated patients, respectively, and −0.05±0.9 mm3 and −0.08±4.1 mm3 in patients treated with ADA/MTX.ConclusionsThe REBONE study shows that TOC monotherapy achieves more pronounced repair of existing bone erosions than ADA/MTX. Hence, IL-6 is a central factor for the disturbed bone homeostasis in the joints of patients with RA.

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Section: Discussionmentioning

confidence: 68%

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis

et al. 2019

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“…While these activities pertain primarily to the control of adaptive immunity, both cytokines have influences on stromal tissue responses to inflammation. For example, IL‐6 and IL‐27 play important roles in bone remodelling, where an imbalance between bone resorption and formation contributes to bone destruction in inflammatory arthritis . Here, Il27ra ‐deficient mice with experimental arthritis displayed severe synovitis and synovial hyperplasia, and an increased incidence of focal bone erosions .…”

Section: Il‐6 and Il‐27 In Inflammatory Arthritismentioning

confidence: 95%

IL-27: a double agent in the IL-6 family

Jones

Hill

Cardús

et al. 2018

Clinical and Experimental Immunology

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Summary The cytokine interleukin (IL)‐6 is a major therapeutic target for the treatment of various inflammatory and autoimmune diseases. While IL‐6 receives considerable attention in studies of innate and adaptive immunity, the IL‐6‐related family member IL‐27 is recognized increasingly for its effects on cellular proliferation, differentiation and leucocyte effector functions. Both cytokines activate responses in myeloid and stromal tissue cells, where they direct the transition from innate to adaptive immunity. However, they are identified frequently as lymphokines that control responses in T cells and B cells. In this regard, IL‐27 often opposes the action of IL‐6. Here, we will review the role of IL‐6 and IL‐27 in inflammation, with a particular focus on inflammatory arthritis, and discuss their importance in the diagnosis, stratification and treatment of autoimmune disease.

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“…However, initiation of bone regeneration processes and repair of joint damage have rarely been reported and need further elucidation. (3)(4)(5)(6)(7) Conventional radiography remains the first choice for the assessment of structural bone and cartilage damage in RA patients. On the other hand, novel imaging methods, such as combined positron emission tomography/computed tomography (PET/CT) provide insights into pathophysiological processes together with anatomical localization.…”

Section: Introductionmentioning

confidence: 99%

Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice

Hayer

Zeilinger

Weiss

et al. 2019

Journal of Bone and Mineral Research

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In rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([18F]FDG) and [18F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti‐TNF antibody, for 4 weeks. Before and after treatment period, mice received either [18F]FDG, for detecting inflammatory processes, or [18F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUVmean) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [18F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [18F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti‐TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [18F]FDG µPET/CT imaging allows to quantify and monitor inflammation‐mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

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Pre-treatment interleukin-6 levels strongly affect bone erosion progression and repair detected by magnetic resonance imaging in rheumatoid arthritis patients

Abstract: In newly diagnosed, untreated RA patients, baseline plasma IL-6 levels are responsible for 1-year MRI bone erosion progression and repair.

Cited by 18 publications

References 18 publications

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis

Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis

IL-27: a double agent in the IL-6 family

Multimodal [18F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice

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