Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years

Heijde, Desirée van der; Salonen, David; Weissman, Barbara N.; Landewé, Robert; Maksymowych, Walter P.; Küpper, H.; Ballal, Shaila; Gibson, E; Wong, Robert

doi:10.1186/ar2794

Cited by 371 publications

(206 citation statements)

References 31 publications

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“…An alternative hypothesis was then proposed whereby pathogenetic factors such as altered gene expression, biomechanical factors, and bacteria trigger the concomitant expression of inflammation and new bone formation, which then proceed along essentially autonomous pathways (2). This hypothesis has been advanced to explain the apparent lack of benefit of anti-TNF␣ agents on the radiographic progression of AS (3)(4)(5).…”

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confidence: 99%

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

Chiowchanwisawakit

Lambert

Conner‐Spady

et al. 2011

Arthritis & Rheumatism

179

113

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Objective. Focal fat infiltration is frequently visible on magnetic resonance imaging (MRI) of the spine in patients with ankylosing spondylitis (AS) and likely reflects postinflammatory tissue metaplasia. To support the concept of coupling between inflammation and new bone formation, we tested the hypothesis that focal fat infiltration at a vertebral corner is more likely to evolve into a de novo syndesmophyte.Methods. MRI scans were obtained at baseline and radiographs were obtained at baseline and 2 years in 100 AS patients from 2 cohorts: a clinical trial cohort (n ‫؍‬ 38) and an observational cohort (n ‫؍‬ 62). In the clinical trial cohort, patients were randomized to receive anti-tumor necrosis factor (anti-TNF) therapy or placebo for 12-24 weeks and then open-label treatment for 2 years. In the observational cohort, patients received either standard therapy (n ‫؍‬ 36) or anti-TNF therapy (n ‫؍‬ 26) for 2 years. Vertebral corner inflammation and fat infiltration were assessed independently by pairs of readers who were blinded with regard to the radiographic findings.Results. New syndesmophytes developed significantly more frequently in vertebral corners with fat in both the clinical trial (10.2%) and the observational (6.5%) cohort as compared to those without either Conclusion. Our data lend support to the hypothesis that inflammatory lesions evolve into new bone through a process of tissue metaplasia that includes fat infiltration.A hallmark of ankylosing spondylitis (AS) is the development of new bone in the spine, which typically leads to ankylosis across the disc spaces. Bone proliferation typically starts at the vertebral rim and grows in the direction of the anulus fibrosus, parallel to the vertebral axis. Ossification may extend across the vertical length of the anulus and becomes visible on radiographs as a syndesmophyte.Until recently, it was hypothesized that ankylosis occurred in response to inflammation and following a reparative process that included cartilage metaplasia. However, data from animal models of spondylarthritis (SpA), principally ankylosing enthesitis, directly challenged this hypothesis by demonstrating that anti-tumor necrosis factor ␣ (anti-TNF␣) therapy did not prevent the development of ankylosis (1). An alternative hypothesis was then proposed whereby pathogenetic factors such as altered gene expression, biomechanical factors, and bacteria trigger the concomitant expression of inflammation and new bone formation, which then proceed

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confidence: 99%

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

Chiowchanwisawakit

Lambert

Conner‐Spady

et al. 2011

Arthritis & Rheumatism

179

113

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“…El bloqueo farmacológico con agentes anti TNFalpha en EA controla la inflamación y reduce la extensión del edema de médula ósea por hallazgos en RMN, pero el control de la erosión ósea en la entesis es menos consistente en particular la formación de sindesmofitos 13 . Lo anterior sugiere que dichos procesos no se encuentran completamente acoplados a la inflamación o asociados a factores destructivos específicos de hueso 14 .…”

Section: Factores Destructivos De Huesounclassified

“…Estos hallazgos confirman que el patrón de erosión en EA caracterizado por exceso de formación ósea perióstica, difiere del proceso observado en AR. Así mismo, se correlaciona con los resultados de estudios clínicos en los cuales el bloqueo anti TNF-alpha es menos efectivo para detener el proceso de erosión en comparación con AR 13,14 . Por lo tanto, el impacto del proceso inflamatorio en el hueso es específico de su localización, tipo celular involucrado, citocinas y factores presentes en el microambiente local 19 .…”

Section: Destrucción Vs Neoformaciónunclassified

Remodelación ósea en espondiloartritis

et al. 2013

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Bone remodeling in spondyloarthritisext 5050 e-mail: wbatu@hotmail. com L as espondiloartritis (SpA) corresponden a un grupo heterogéneo de enfermedades cró-nicas caracterizadas por entesitis tanto axial como periférica, artritis y manifestaciones extraarticulares. Las alteraciones radiológicas observadas en dichos pacientes revelan cambios erosivos en los ángulos de los cuerpos vertebrales en estadios tempranos de la enfermedad y proliferación de estructuras óseas conocidas como sindesmofitos hallados en fases más tardías. La fusión de sindesmofitos en los cuerpos vertebrales adyacentes, originan el aspecto radiológico de la columna vertebral conocido como "caña de bambú". Como evento final, la anquilosis conlleva a la pérdida de funcionalidad de las estructuras articulares comprometidas. El uso de antiinflamatorios no esteroideos (AINES) o el bloqueo farmacológico del factor de necrosis tumoral alfa (TNF-alpha), han evidenciado que no detienen la progresión de la erosión ósea acelerada y/o formación de sindesmofitos 1,2 .Estudios de asociación del genoma humano han identificado el papel de genes adicionales no relacionados con el complejo mayor de histocompatibilidad (CMH) en la fisiopatología de la enfermedad y varias hipótesis han surgido con el fin de explicar su patogenia. Por lo tanto, el área de conocimiento relacionada con remodelación ósea es actualmente foco de investigación activa a nivel mundial, con un aumento progresivo en el número de publicaciones durante los últimos años.La presente revisión recoge la evidencia actual respecto al papel que tiene el proceso de remodelación ósea -proliferación y resorción-en la vía fisiopatológica en espondiloartritis. Se realizó una búsqueda en Medline (Pubmed) utilizando los siguientes términos MESH: «bone remodelling», «bone remodelling process», «spondyloarthritis», y «ankylosing spondylitis», sin límite de años de bús queda. Posteriormente, mediante búsqueda manual se ampliaron las fuentes dentro de las bibliografías de las referencias originales.

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“…The goal of treatment of axial SpA is to obtain the suppression of symptoms but also the prevention of structural bone damage and of ankylosis. The studies on anti-TNF agents in longstanding axial disease have demonstrated that the structural damaged cannot be prevented and that it is independent from the presence of absence of inflammatory activity (13)(14)(15). A great effort should be done to increase the referral of every axial SpA patient to the rheumatologist.…”

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confidence: 99%

Anti-TNF agents for the treatment of active non-radiographic axial spondyloarthritis

Olivieri

D’Angelo²,

Palazzi

et al. 2013

Reumatismo

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The spondyloarthritis (SpA) complex includes ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, arthritis related to inflammatory bowel disease and forms that do not meet established criteria for these definite categories which are designated as undifferentiated SpA. In the early 1990s, two sets of classification criteria were suggested with the purpose to cover the whole clinical spectrum of SpA: the Amor criteria and the European Spondylarthropathy Study Group (ESSG) criteria..

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Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years

Cited by 371 publications

References 31 publications

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

Focal fat lesions at vertebral corners on magnetic resonance imaging predict the development of new syndesmophytes in ankylosing spondylitis

Remodelación ósea en espondiloartritis

Anti-TNF agents for the treatment of active non-radiographic axial spondyloarthritis

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