Serum Vascular Endothelial Growth Factor Levels Lack Predictive Value in Patients with Active Ankylosing Spondylitis Treated with Golimumab

Braun, Jürgen; Baraliakos, Xenofon; Hermann, Kay-Geert A.; Xu, Stephen; Hsu, Benjamin

doi:10.3899/jrheum.150897

Cited by 14 publications

(9 citation statements)

References 21 publications

(28 reference statements)

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“…These showed that CRP was consistently associated with progression while limited data from isolated reports also implicated additional inflammatory biomarkers such as serum IL6 and calprotectin (16, 21–26). Data supporting a prognostic role for vasoactive endothelial growth factor could not be replicated (44, 45).…”

Section: Prognostic Biomarkersmentioning

confidence: 99%

Biomarkers for Diagnosis of Axial Spondyloarthritis, Disease Activity, Prognosis, and Prediction of Response to Therapy

Maksymowych

2019

Front. Immunol.

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There exists a major unmet need for biomarkers that can identify axial spondyloarthritis (axSpA) early after disease onset because of the availability of highly effective therapies. Several recent reports have examined the autoantibody response in patients with axSpA through the use of protein microarrays and protein-protein interactions although diagnostic performance of biomarkers identified to date has been inadequate. An example of such a biomarker is protein phosphatase magnesium-dependent 1A. Antibodies to the human leukocyte antigen class II-associated invariant chain peptide (anti-CD74) are candidate diagnostic biomarkers but sensitivity declines with increasing duration of disease. Metabolomic studies have employed nuclear magnetic resonance (NMR) spectrometry to identify disease-specific metabolites related to fat metabolism and intestinal microbial metabolism. A second major unmet need exists for biomarkers of disease activity that have superiority over standard C-reactive protein assessment and reflect MRI inflammation in the axial spine. Several biomarkers reflecting inflammation (calprotectin), angiogenesis (vasoactive endothelial growth factor), and connective tissue turnover (C2M, C3M, and citrullinated metalloproteinase degraded fragment of vimentin) have recently been shown to reflect disease activity when compared with clinical outcomes but comparisons with MRI inflammation are very limited. With increasing availability of highly effective but costly therapies, a third unmet need is biomarkers that can predict response to therapies with different mechanisms of action and are superior to C-reactive protein. Calprotectin is currently the only candidate. Although there are as yet no proven therapies for preventing progression of disease there is an unmet need for biomarkers of prognosis that are more responsive than radiography. Aside from CRP no consistent candidates have emerged. Future studies will need to be prospective, include consecutive patients presenting with undiagnosed back pain, and use more reliable and objective endpoints such as MRI inflammation. Moreover, it has become evident that targeted biomarker studies have not been successful in identifying clinically useful biomarkers and technologies that can simultaneously assess “multiomic” markers will need to be analyzed for future advances. These include more sophisticated metabolomic profiling and universal metabolome-standard (UMS) methodology, next generation RNA sequencing, and affinity-based quantitative proteomics based on the use of nucleic acid binders such as the aptamer-based SOMAscan assay.

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Section: Prognostic Biomarkersmentioning

confidence: 99%

Biomarkers for Diagnosis of Axial Spondyloarthritis, Disease Activity, Prognosis, and Prediction of Response to Therapy

Maksymowych

2019

Front. Immunol.

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“…Early assessment and treatment of patients are important considering that significant regression of spinal inflammation can occur as early as 6 weeks after TNFi treatment (90), and that mobility limitation correlates with inflammation in the early phases of the disease (91). Ongoing systemic inflammation as measured by CRP values despite TNFi therapy is a factor predicting the development of radiographic progression (92), suggesting that effective suppression of inflammation, including MRI inflammation, may be important for effective disease modification. Whether an early suppression of inflammation leads to a decrease risk for new bone formation, though, remains to be demonstrated.…”

Section: Resultsmentioning

confidence: 99%

Imaging in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and osteoarthritis: An international viewpoint on the current knowledge and future research priorities

et al. 2019

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Imaging is increasingly used in the routine management of rheumatic diseases as well as in the clinical trials of these disorders. This viewpoint, authored by a group of international imaging experts following two meetings dedicated to imaging in rheumatology, reports a consensus about the current knowledge and addresses where further research should be focused based on the views of the international imaging experts and discussion of the evidence with attending imaging practitioners. The goal was to maximize the potential of imaging to improve the clinical management of four rheumatic diseases. These rheumatic diseases include rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and osteoarthritis.

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“…Even the number of colonies in culture failed to differentiate between these categories. Braun and colleagues reported serum VEGF in AS to be not predictive for radiographic progression of the disease [38]. Only few data are available on serum angiopoietins and SpA.…”

Section: Discussionmentioning

confidence: 99%

Humoral and Cellular Patterns of Early Endothelial Progenitor Cells in Relation to the Cardiovascular Risk in Axial Spondylarthritis

Patschan¹,

Vogt²,

Bakhtiari³

et al. 2019

J Clin Med Res

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Background Spondylarthritis (SpA) significantly affects sacroiliac, intervertebral and peripheral joints. Patients with SpA suffer from increased cardiovascular risk (CVR). The endothelial progenitor cell (EPC) system critically perpetuates vascular repair. The aim of the study was to evaluate circulating EPCs in axial (ax)SpA with special attention on parameters of disease activity and CVR. Methods Disease activity and functional impairment were quantified in 50 axSpA patients by using standardized parameters (Bath ankylosing spondylitis disease activity index (BASDAI), C-reactive protein (CRP), finger-floor distance (FFD) and Ott’ sign). Circulating EPCs and EPC regeneration were analyzed (fluorescence-activated cell sorting (FACS) and colony-forming unit (CFU) assay). Serum vasomodulatory mediators were quantified by enzyme-linked immunosorbent assay (ELISA). Results EPC colony numbers were lower in axSpA as compared to controls. Females displayed more colonies than males. In addition, fewer colonies were observed in smokers, in patients with a BASDAI of below 4 and in hypertension. Circulating CD133 + /KDR + cells did not differ between the groups. Follow-up analysis (33 months later) did not show any differences in gender, colony formation, CD133 + /KDR + cells or serum levels of vasomodulatory mediators if related to the categories of BASDAI, Ott’ sign or FFD. Conclusions EPC colony formation is significantly affected in axSpA with particularly low levels in males. EPC-related parameters do not allow predicting disease activity-related or functional parameters nor are they useful for CVR assessment in SpA.

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Serum Vascular Endothelial Growth Factor Levels Lack Predictive Value in Patients with Active Ankylosing Spondylitis Treated with Golimumab

Cited by 14 publications

References 21 publications

Biomarkers for Diagnosis of Axial Spondyloarthritis, Disease Activity, Prognosis, and Prediction of Response to Therapy

Biomarkers for Diagnosis of Axial Spondyloarthritis, Disease Activity, Prognosis, and Prediction of Response to Therapy

Imaging in rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and osteoarthritis: An international viewpoint on the current knowledge and future research priorities

Humoral and Cellular Patterns of Early Endothelial Progenitor Cells in Relation to the Cardiovascular Risk in Axial Spondylarthritis

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