scholarly journals Secukinumab in axial spondyloarthritis: a narrative review of clinical evidence

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110418
Author(s):  
Jürgen Braun ◽  
Uta Kiltz ◽  
Björn Bühring ◽  
Xenofon Baraliakos
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Human Leukocyte ◽  
Signs And Symptoms ◽  
Axial Skeleton ◽  
Narrative Review ◽  
The European Union ◽  
New Bone Formation

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease characterized by inflammation and new bone formation in the axial skeleton. AxSpA is considered a spectrum of disease that includes two subtypes identified by the Assessment in SpondyloArthritis International Society classification criteria, namely, radiographic (r-axSpA usually referred to as ankylosing spondylitis) and non-radiographic axSpA (nr-axSpA). Although the burden of disease appears similar between the two classified subtypes, the degree of inflammation, as assessed by magnetic resonance imaging and C-reactive protein, and the degree of new bone formation are significantly higher in r-axSpA than in nr-axSpA. Nevertheless, axSpA is considered one disease with different courses. International guidelines for the management of axSpA have outlined treatment goals focused on control of signs and symptoms, inflammation, prevention of progressive structural damage, preservation of physical function, normalization of social participation and improvement of quality of life. The pathogenesis of axSpA has not been completely elucidated to date. A strong link between human leukocyte antigen B27 and axSpA, however, has been identified, and the success of anti-tumour necrosis factor and anti-interleukin (IL)-17A therapy has highlighted some of the key pro-inflammatory cytokines involved. The anti-IL-17A monoclonal antibody secukinumab is approved for the treatment of ankylosing spondylitis and nr-axSpA in the European Union and United States. In this narrative review, we discuss data for secukinumab in axSpA from randomized controlled trials, including MEASURE trials in AS and PREVENT in nr-axSpA, and real-world evidence.

Significance of structural changes in the sacroiliac joints of patients with axial spondyloarthritis detected by MRI related to patients symptoms and functioning

2021 ◽  
pp. annrheumdis-2021-221406
Author(s):  
Juergen Braun ◽  
Uta Kiltz ◽  
Xenofon Baraliakos
Keyword(s):  
Bone Formation ◽  
Structural Damage ◽  
Structural Changes ◽  
Axial Spondyloarthritis ◽  
Conventional Radiography ◽  
Axial Skeleton ◽  
Interleukin 17 ◽  
New Bone Formation ◽  
Sacroiliac Joints ◽  
Magnetic Resonance Imaging Mri

Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease that manifests primarily in the axial skeleton, initially mostly in the sacroiliac joints (SIJ), usually later spreading to the spine. The disease is characterised by inflammation and new bone formation which are mainly assessed by conventional radiography (CR) and magnetic resonance imaging (MRI). Tumour necrosis factor inhibitors (TNFi) and interleukin-17 antagonists have been shown to be efficacious and efficient in patients with axSpA. This treatment seems to also inhibit structural damage, for example, retard radiographic progression. Indeed, a reduction of new bone formation in the spine, as assessed by CR, has been reported to occur after at least 2 years of therapy with TNFi. Recently, a reduction of erosions and ankylosis in the SIJ has also been observed in axSpA patients treated with etanercept and filgotinib. In this narrative review, we discuss the limited significance of such findings.

Axial Spondyloarthritis and New Bone Formation

2021 ◽  
Vol 30 (04) ◽  
pp. 311-318
Author(s):  
Uta Syrbe
Keyword(s):  
Bone Formation ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Clinical Symptoms ◽  
Research Work ◽  
New Bone Formation ◽  
Sacroiliac Joints ◽  
Spine Mobility ◽  
Vertebral Bodies ◽  
Inflammatory Changes

AbstractAxial spondyloarthritis is an inflammatory disease of the axial skeleton. Its pathogenesis is only partly understood. At the beginning, there are inflammatory changes in the sacroiliac joints which are followed by inflammation in vertebral bodies and in facet joints. Low back pain occurring in the morning hours is the dominant clinical symptom. In the early phase, inflammatory changes are detectably by MRI. Inflammation promotes a process of joint remodelling in the sacroiliac joints which leads to erosions, sclerosis and bony bridging, i. e. ankylosis, which are detectable by X-ray. In the spine, vertical osteophytes developing at sites of previous inflammation connect vertebral bodies as syndesmophytes. Additional ossification of longitudinal ligaments contributes to the so-called bamboo spine. Ossification of the spine promotes fixation of a severe kyphosis of the thoracic spine which strongly impairs spine mobility and quality of life. High disease activity seems a prominent risk factor for development of structural damage. However, although NSAIDs improve clinical symptoms, they do not reduce new bone formation. In contrast, TNFα and IL-17 inhibitors seem to retard new bone formation apart from their clinical efficacy. Research work of the last years identified immunological pathways of inflammation. However, the trigger and cellular components of the immune reaction in the bone marrow are still poorly defined. Osteoclasts are involved in the destruction of the subchondral bone, while osteoblasts facilitate new bone formation and cartilage ossification. This review gives an overview about diagnostics and therapy of axSpA and about risk factors for the development of structural damage. Concepts about the immune pathogenesis and joint remodeling in AS are given under recognition of genetic and histopathological studies.

Pathology: bone

2016 ◽  
Author(s):  
Rik J. Lories ◽  
Georg Schett
Keyword(s):  
Bone Formation ◽  
Structural Damage ◽  
Axial Spondyloarthritis ◽  
Signalling Pathways ◽  
New Bone Formation ◽  
Different Types ◽  
Significant Burden ◽  
Current Therapies ◽  
Developmental Signalling ◽  
Biomechanical Factors

Axial spondyloarthritis is associated with different types of skeletal damage. Inflammation at the affected sites is linked with both loss of trabecular bone and new bone formation on the cortical side, potentially leading to joint or spine ankylosis. Both aspects of the disease can result in a significant burden for the patient. Bone loss is directly linked to proinflammatory cytokines and activation of osteoclasts. Control of inflammation is therefore the best strategy to prevent loss of bone. The nature of the new bone formation process is less defined. A prominent role for developmental signalling pathways has been proposed. Current therapies have limited or no impact on this process. However, emerging data suggest that early control of disease activity may be part of a window of opportunity to prevent structural damage, as biomechanical factors and instability following inflammation may also play a role.

scholarly journals The role of bone morphogenetic proteins in ankylosing spondylitis

2012 ◽  
Vol 4 (4) ◽  
pp. 293-299 ◽  
Author(s):  
Shea Carter ◽  
Kirsten Braem ◽  
Rik J. Lories
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Drug Targets ◽  
Spinal Fractures ◽  
Axial Skeleton ◽  
Spinal Mobility ◽  
Endochondral Bone Formation ◽  
New Bone Formation ◽  
Increased Risk

Ankylosing spondylitis (AS), the best-known form of spondyloarthritis (SpA), is a remodelling arthritis characterized by chronic inflammation and bone formation. Ankylosis of the axial skeleton and sacroiliac joints leads to an impairment of spinal mobility, progressive spinal fusion and an increased risk of spinal fractures. The nature of the relationship between inflammation and new bone formation in AS has been controversial and questions remain as to whether there is a direct relationship between inflammation and new bone formation. Like others, we have hypothesized that the molecular pathways underlying ankylosis recapitulate the process of endochondral bone formation and that bone morphogenetic proteins (BMPs) play a key role in this process in AS. Furthermore, we discuss the entheseal stress hypothesis, which proposes that inflammation and ankylosis are linked but largely independent processes, and consider observations from mouse models and other human diseases which also imply that biomechanical factors contribute to the pathogenesis of AS. As current therapeutics, such as tumour necrosis factor inhibitors do not impede disease progression and ankylosis in AS, it is the pathways discussed in this review that are the now the focus for the identification of future drug targets.

scholarly journals AB1087 DETECTING AXIAL AND PERIPHERAL NEW BONE FORMATION IN SPONDYLOARTHRITIS PATIENTS USING [18F]FLUORIDE PET-CT IMAGING

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1832.2-1833
Author(s):  
J. De Jongh ◽  
R. Hemke ◽  
G. C. J. Zwezerijnen ◽  
M. Yaqub ◽  
I. Van der Horst-Bruinsma ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Ct Imaging ◽  
Whole Body ◽  
Therapeutic Effects ◽  
New Bone Formation ◽  
Research Support ◽  
Patella Tendon ◽  
Pet Ct ◽  
18F Fluoride

Background:Bone formation in spondyloarthritis (SpA) is presumably related to local enthesitis/peri-articular inflammation and ultimately may lead to functional limitation (1,2). X-rays only allow long-term monitoring of bone formation (≥2 years) (3). Imaging techniques that can visualize bone formation at an early stage would therefore be valuable. Positron Emission Tomography (PET) using [18F]Fluoride can visualize and quantify (early changes in) bone formation at molecular level (4).Objectives:To investigate the feasibility of [18F]Fluoride to assess new bone formation at axial and peripheral enthesial sites in SpA patients.Methods:Thus far, 5 of the total of 15 patients with clinically active ankylosing spondylitis (AS) (according to modified New York criteria and BASDAI ≥4) and 8 of the 25 patients with active psoriatic arthritis (PsA) (according to CASPAR criteria and ≥1 clinically active enthesitis) were included. Of each patient, a whole body [18F]Fluoride PET-CT scan was performed. All scans were visually judged and scored dichotomously by one reader (blinded for clinical data) for PET-positive lesions in the spine, peripheral enthesis sites and joints. Low dose CT was used for anatomical reference.Results:The study is ongoing, with whole body [18F]Fluoride PET-CT scans available in five AS patients and eight PsA patients. In 4/5 AS scans, at least (≥1) PET positive lesions were found in the cervical, thoracic and/or lumbar vertebrae. These were mainly found in anterior corners of vertebrae and bridging syndesmophytes (Fig. 1A). In all eight PsA patients, at least 1 PET positive lesion was visualized, projected either at the site of a tendon attachment (fascia plantaris, achilles- and patella tendon (Fig 1B)) or peri-articularly (in the ankle or wrist).Fig 1.[18F]Fluoride uptake in the cervical, thoracic and lumbar spine in a clinically active AS patient (A) and in the patella tendon of the right knee in a clinically active PsA patient (B)Conclusion:[18F]Fluoride PET uptake, reflecting new bone formation, can be visualized at heterogeneously distributed enthesis and (peri-)articular sites in AS- and PsA patients. The technique therefore is sensitive to visualize new bone formation and may reflect local disease activity. Additional scans will be collected and analyzed quantitatively, also after anti-TNF or Secukinumab treatment, to further investigate the applicability of [18F]Fluoride PET for monitoring of therapeutic effects on bone formation in SpA.References: :[1]Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68(6):948-53.[2]Rezvani A, Bodur H, Ataman S, Kaya T, Bugdayci DS, Demir SE, et al. Correlations among enthesitis, clinical, radiographic and quality of life parameters in patients with ankylosing spondylitis. Mod Rheumatol. 2014;24(4):651-6.[3]Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 2005;52:1000-8..[4]Bruijnen ST, Verweij NJF, van Duivenvoorde L, Bravenboer N, Baeten D, van Denderen JC, et al. [18F]Fluoride PET-CT imaging of bone formation in ankylosing spondylitis before and after 12 weeks of anti-TNF treatment. 2017.Acknowledgments:We thank EULAR Foreum, Pfizer and Novartis for financial support of this investigator initiated study.Disclosure of Interests:Jerney de Jongh: None declared, Robert Hemke: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Marleen G.H. van de Sande Grant/research support from: Novartis, Eli lily, UCB, Jansen, Consultant of: Abbvie, Novartis, Eli lily, MSD, Arno Van Kuijk: None declared, Irene Bultink: None declared, Lot Burgemeister: None declared, Nancy M.A. van Dillen: None declared, Alexandre Voskuyl: None declared, Conny J. van der Laken: None declared

OP0111 Mechanism of New Bone Formation in Ankylosing Spondylitis: the Role of IL-32 in Osteoblast Differentiation

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 103.1-103
Author(s):  
S. Hong ◽  
E.-J. Lee ◽  
Y.J. Kim ◽  
B.S. Koo ◽  
E.-J. Chang ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Bone Formation ◽  
Osteoblast Differentiation ◽  
New Bone Formation

scholarly journals Canada-Denmark MRI scoring system of the spine in patients with axial spondyloarthritis: updated definitions, scoring rules and inter-reader reliability in a multiple reader setting

RMD Open ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. e001057 ◽  
Author(s):  
Simon Krabbe ◽  
Mikkel Østergaard ◽  
Susanne J Pedersen ◽  
Ulrich Weber ◽  
Georg Kröber ◽  
...  
Keyword(s):  
Bone Formation ◽  
Scoring System ◽  
Axial Spondyloarthritis ◽  
Comprehensive Evaluation ◽  
Bone Erosion ◽  
Intraclass Correlation ◽  
New Bone Formation ◽  
Good Reliability ◽  
Single Measure ◽  
Reader Reliability

ObjectiveTo validate the Canada-Denmark (CANDEN) MRI scoring system for the spine in axial spondyloarthritis with updated lesion definitions.MethodsLesion definitions in the CANDEN system were updated and illustrated by a consensus set of reference images. Sagittal spine MRIs of 40 patients with axial spondyloarthritis obtained at baseline and at week 52 after initiation of treatment with the tumour necrosis factor inhibitor golimumab were evaluated in unknown chronology by seven readers blinded to all other data.ResultsCANDEN MRI spine inflammation score had very good reliability for status scores (single-measure intraclass correlation coefficient (ICC) of 21 reader pairs median of 0.91 (IQR 0.88–0.92)) and change scores (ICC 0.88 (0.86–0.92)). CANDEN MRI spine fat score had good to very good reliability for status scores (ICC 0.79 (0.75–0.86)) and moderate to good reliability for detecting change (ICC 0.59 (0.46–0.73)). CANDEN MRI spine bone erosion score and CANDEN MRI spine new bone formation score had slight to moderate reliability for status scores (ICC 0.38 (0.32–0.52) and 0.39 (0.27–0.49), respectively).ConclusionThe CANDEN MRI spine scoring system allows a comprehensive evaluation of inflammation, fat, bone erosion and new bone formation of the spine in patients with axial spondyloarthritis. It demonstrated very good reliability for detecting change in inflammation, moderate to good reliability for detecting change in fat, and slight to moderate reliability for detecting bone erosions and new bone formation. Studies with longer follow-up or patients with more advanced spinal involvement may be needed to reliably detect change in bone erosion and new bone formation scores.Trial registration numberNCT02011386.

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