46 results on '"Sieper, Joachim"'
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2. Geschichte der Biologikatherapie bei axialer Spondyloarthritis – Teil 2.
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Sieper, Joachim and Braun, Jürgen
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Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2023
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3. The IL-23-IL-17 pathway as a therapeutic target in axial spondyloarthritis.
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Sieper, Joachim, Poddubnyy, Denis, and Miossec, Pierre
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PSORIATIC arthritis , *ANIMAL models of inflammation , *PATHOLOGY , *ANKYLOSING spondylitis , *MONOCLONAL antibodies , *BONE marrow - Abstract
The cytokines IL-23 and IL-17 have an important role in the pathogenesis of, and as a therapeutic target in, both animal models of chronic inflammation and some human chronic inflammatory diseases. The traditional view is that a main source of IL-17 is T cells and that IL-17 production is under the control of IL-23. IL-17 inhibition has shown good efficacy in clinical trials for ankylosing spondylitis (AS), a subtype of axial spondyloarthritis (axSpA) characterized by radiographic evidence of sacroiliitis. On the basis of data from animal models, genetic studies and the investigation of tissue and blood samples from patients with AS, IL-23 had also been predicted to be important in the pathogenesis of this disease and was therefore considered a potential therapeutic target for axSpA. However, two placebo-controlled, double-blind clinical trials in axSpA of monoclonal antibodies directed against either the p40 protein or the p19 protein of the IL-23 molecule had clear negative results. These findings indicate that IL-23 and IL-17 are at least partly uncoupled in axSpA. Reasons as to why, when and how such an uncoupling might occur are discussed in this Review, with special reference to the unique microenvironment of the subchondral bone marrow in axSpA. [ABSTRACT FROM AUTHOR]
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- 2019
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4. Mechanism of New Bone Formation in Axial Spondyloarthritis.
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Poddubnyy, Denis and Sieper, Joachim
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Purpose of the review: The purpose of this review is to discuss new evidence explaining the progress from bony inflammation over repair tissue to new bone formation in axial spondyloartrhitis and its correlations in imaging and histology of the bone. Recent findings: Data from imaging, histology and treatment interventions indicates that the disease starts with inflammation, followed by replacement of subchondral bone marrow by repair tissue which presence is crucial for the stimulation of new bone formation. The magnetic resonance imaging (MRI) sequences of STIR and T1 are currently the most commonly used imaging techniques to follow this process; explanations are offered for the limited sensitivity to detect these bony changes on MRI in their different phases. Summary: Early and effective anti-inflammatory treatment is crucial for the prevention of long-term ankylosis. Whether there are currently also treatment options targeting new bone formation in these patients directly is less clear. [ABSTRACT FROM AUTHOR]
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- 2017
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5. Synovial cell production of IL-26 induces bone mineralization in spondyloarthritis.
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Heftdal, Line, Andersen, Thomas, Jæhger, Ditte, Woetmann, Anders, Østgård, René, Kenngott, Elisabeth, Syrbe, Uta, Sieper, Joachim, Hvid, Malene, Deleuran, Bent, and Kragstrup, Tue
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SPONDYLOARTHROPATHIES ,BONE density ,SYNOVIAL fluid ,INTERLEUKINS ,FLOW cytometry ,THERAPEUTICS - Abstract
Spondyloarthritis (SpA) is characterized by inflammation and new bone formation and can be treated by inhibition of the proinflammatory cytokines TNF-α and IL-17A. IL-26 is considered a proinflammatory cytokine, predominantly related to Th17 cells. In the present study, we investigate IL-26 expression in SpA patients, and examine the in vitro production of IL-26 by synovial cells and the effects of IL-26 on human osteoblasts. IL-26 was measured by ELISA in plasma and synovial fluid (SF) of 15 SpA patients and in plasma samples from 12 healthy controls. Facet joints from axial SpA patients were stained for IL-26 and analyzed by fluorescence microscopy. Synovial fluid mononuclear cells, C-C motif chemokine receptor 6 memory Th17 cells, and fibroblast-like synoviocytes (FLSs) were isolated, and supernatants were analyzed for IL-26 content by ELISA. FLSs were further stained for IL-26 production and the myofibroblast marker α-smooth-muscle-actin (αSMA) and analyzed by flow cytometry. Human osteoblasts were cultured in the presence of IL-26, and the degree of mineralization was quantified. We found that IL-26 levels in SF were increased compared with plasma ( P < 0.0001). Moreover, IL-26 expression was found in facet joints of axial SpA patients within the bone marrow. IL-26 secretion was primarily found in αSMA myofibroblasts. In contrast, Th17 cells did not produce detectable amounts of IL-26. Human osteoblasts treated with IL-26 showed increased mineralization compared with untreated osteoblasts ( P = 0.02). In conclusion, IL-26 seems to be produced by myofibroblasts in the inflamed synovium and could be a possible facilitator of bone mineralization in SpA. Key messages: [ABSTRACT FROM AUTHOR]
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- 2017
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6. New evidence on the management of spondyloarthritis.
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Sieper, Joachim and Poddubnyy, Denis
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ANKYLOSING spondylitis treatment , *ANTIRHEUMATIC agents , *C-reactive protein , *INFLAMMATION , *NONSTEROIDAL anti-inflammatory agents , *DIPHOSPHONATES , *THERAPEUTIC use of monoclonal antibodies , *THERAPEUTIC use of proteins , *ANKYLOSING spondylitis , *MAGNETIC resonance imaging , *RADIOGRAPHY , *SPONDYLOARTHROPATHIES , *TUMOR necrosis factors , *DISEASE management , *CHEMICAL inhibitors ,THERAPEUTIC use of glucocorticoids - Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for patients with symptomatic axial spondyloarthritis (SpA), who seem to respond best if treated early in the course of disease. The effect of NSAIDs on radiographic disease progression is less clear. Conventional disease-modifying antirheumatic drugs (DMARDs) are not recommended in the treatment of axial SpA, either alone or in combination with TNF blockers. Patients with nonradiographic axial SpA (nr-axSpA) seem to respond as well to TNF blockers as do patients with radiographic axial SpA (ankylosing spondylitis (AS)). However, patients with nr-axSpA should, in addition to a high severity of symptoms, also have objective signs of inflammation, detectable by MRI or by C-reactive protein testing, to be treated with TNF blockers. Whether early TNF-blocker treatment can retard new bone formation needs clarification. In clinical trials, anti-IL-17 agents and TNF blockers showed similar efficacy in patients with AS. The potential of IL-23 blockade for treatment of axial SpA needs to be further investigated. Treatment options for peripheral SpA have been much less thoroughly investigated than those for axial SpA. However, some data indicate that TNF blockers are effective for treating peripheral arthritis, enthesitis and dactylitis, the typical manifestations of peripheral SpA. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Imaging in Axial Spondyloarthritis.
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Sieper, Joachim and Braun, Jürgen
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- 2014
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8. Management of Axial Spondyloarthritis.
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Sieper, Joachim and Braun, Jürgen
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- 2014
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9. Introduction.
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Sieper, Joachim and Braun, Jürgen
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- 2014
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10. FrontMatter.
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Sieper, Joachim and Braun, Jürgen
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- 2014
11. Diagnosis of Axial Spondyloarthritis.
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Sieper, Joachim and Braun, Jürgen
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- 2014
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12. Clinical Manifestations of Axial Spondyloarthritis.
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Sieper, Joachim and Braun, Jürgen
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- 2014
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13. Overview of Axial Spondyloarthritis.
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Sieper, Joachim and Braun, Jürgen
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- 2014
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14. Clinical manifestations of ankylosing spondylitis.
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Sieper, Joachim and Braun, Jürgen
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The main clinical symptoms in AS are pain and stiffness of the back, predominantly of the lower back and the pelvis, but any part of the spine can be involved. Typical for AS/spondyloarthritis (SpA) is inflammatory back pain (IBP) which is defined clinically and not by laboratory tests such as C–reactive protein (CRP) or erythrocyte sedimentation rate (ESR). Patients complain about morning stiffness of the back, with improvement on exercise but not by rest. In addition, or alternatively, they report awakening at night, mostly in the second half of the night, because of back pain which improves on getting up and moving around (Figure 3.1). Furthermore, back pain should be chronic (>3 months duration) not acute, and it should occur for the first time before the age of 45 years, because the disease starts at a young age; this also helps to differentiate it from degenerative spine disease, the prevalence of which increases with age. Most patients report a mixture of pain and stiffness in the spine, although either can be the main or only symptom. [ABSTRACT FROM AUTHOR]
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- 2011
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15. FrontMatter.
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Sieper, Joachim and Braun, Jurgen
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- 2011
16. Diagnosis of ankylosing spondylitis.
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Sieper, Joachim and Braun, Jürgen
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According to the modified New York criteria, which are still widely used, the hallmark for the diagnosis of AS has been the detection of sacroiliitis by radiographs (Figure 4.1) [2]. Sacroiliitis is graded using a scoring system as shown in Figure 4.2. A diagnosis of AS can be made if sacroiliitis grade 2 bilaterally or grade 3 or higher unilaterally is present together with one clinical criterion, such as the presence of the clinical symptom inflammatory back pain or restriction of spinal mobility. As spinal involvement with the development of syndesmophytes normally occurs later in the course of the disease and as the spine is rarely affected without the sacroiliac (SI) joint, radiographic changes of the spine are not part of these diagnostic criteria. Examples of normal and abnormal sacroiliac joints are shown in Figures 4.3–4.5. [ABSTRACT FROM AUTHOR]
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- 2011
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17. Imaging in ankylosing spondylitis.
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Sieper, Joachim and Braun, Jürgen
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Radiographs and magnetic resonance imaging (MRI) for sacroiliac (SI) joints and the spine are the most important imaging techniques for the diagnosis and followup of patients with spondyloarthritis (SpA), including response to treatment. If other sites outside the axial skeleton are affected they can also be investigated by these methods. In general, radiographs should not be performed more frequently than every 2 years because (chronic) changes occur slowly and investigations with MRI can be used more frequently, according to the clinical situation. [ABSTRACT FROM AUTHOR]
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- 2011
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18. Overview of ankylosing spondylitis.
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Sieper, Joachim and Braun, Jürgen
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The term `spondyloarthritis΄ (SpA) comprises AS, reactive arthritis, arthritis/spondylitis associated with psoriasis, and arthritis/spondylitis associated with inflammatory bowel disease (IBD). There is considerable overlap between the single subsets (Figure 2.1). The main link between each is the association with the human leukocyte antigen (HLA)–B27, the same pattern of peripheral joint involvement with an asymmetrical, often pauciarticular, arthritis, predominantly of the lower limbs, and the possible occurrence of sacroiliitis, spondylitis, enthesitis, dactylitis and uveitis. All SpA subsets can evolve into AS, especially in those patients who are positive for HLA–B27. The SpA subsets can also be split into patients with predominantly axial and predominantly peripheral SpA (Figure 2.2), with an overlap between the two parts in about 20–40% of cases. Through use of such a classification the presence or absence of evidence for a preceding gastrointestinal or urogenital infection, psoriasis or IBD is recorded but does not result in a different classification. The term `predominant axial SpA΄ covers patients with classic AS and those with non–radiographic axial SpA [4]. The latter group of patients would not have radiographic sacroiliitis according to the modified New York criteria, but would normally have evidence of active inflammation as shown by magnetic resonance imaging (MRI) or other means (discussed in more detail in Chapter 5). [ABSTRACT FROM AUTHOR]
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- 2011
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19. Management of ankylosing spondylitis.
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Sieper, Joachim and Braun, Jürgen
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Recently, the Assessment of SpondyloArthritis international Society (ASAS) and European League Against Rheumatism (EULAR) recommendations on the management of AS have been published, based on a thorough analysis of the available literature and on a meeting of spondyloarthritides (SpA) experts. These recommendations are shown in Figures 6.1 and 6.2 [54]. Non–drug approaches are part of the therapy at all stages of the disease. For the predominantly axial manifestation, the treatment options are limited to non–steroidal anti–inflammatory drugs (NSAIDs) as a kind of basic treatment, followed by tumour necrosis factor (TNF)–blocker therapy if this conventional treatment fails. If the clinical picture is dominated by peripheral symptoms such as arthritis or enthesitis, treatment with sulfasalazine and/or local steroid injection should be tried first before TNF blockers are considered. [ABSTRACT FROM AUTHOR]
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- 2011
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20. BackMatter.
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Sieper, Joachim and Braun, Jurgen
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- 2011
21. Spondylitis ankylosans als neue Indikation für Etanercept.
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Burmester, Gerd-Rüdiger and Sieper, Joachim
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Copyright of Etanercept - Therapeutische Anwendungen in Klinik und Praxis is the property of Springer eBooks and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2005
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22. Treatment Challenges in Axial Spondylarthritis and Future Directions.
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Sieper, Joachim
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Major progress has been made in recent years in the management of axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). Most predictors of response have been defined for TNF-blocker therapy, and new treatment strategies are being discussed about how to best reach remission and how to maintain remission. Other biologics besides TNF-blockers have been tested in AS but have so far failed. The IL-17/IL-23 cytokines currently seem to be the most interesting targets. Short-term TNF-blocker therapy does not inhibit radiographic progression but long-term might do so. NSAIDs have been proven to inhibit such progression, even after 2 years of treatment. The effect of a combined therapy of NSAIDs with TNF-blockers on the inhibition of new bone formation in AS patients is currently unknown. [ABSTRACT FROM AUTHOR]
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- 2013
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23. Relationship of bone mineral density with disease activity and functional ability in patients with ankylosing spondylitis: a cross-sectional study.
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Grazio, Simeon, Kusić, Zvonko, Cvijetić, Selma, Grubišić, Frane, Balenović, Antonija, Nemčić, Tomislav, Matijević-Mikelić, Valentina, Punda, Marija, and Sieper, Joachim
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ANKYLOSING spondylitis ,SPONDYLITIS ,C-reactive protein ,BONE density ,RHEUMATOLOGY - Abstract
In ankylosing spondylitis, inflammatory activity probably plays a key role in the pathophysiology of bone loss. The aim of the study was to investigate the relationship of bone mineral density (BMD) at the lumbar spine and hip region with some measures of disease activity and functional ability in patients with ankylosing spondylitis. In 80 patients with established ankylosing spondylitis, disease activity and functional ability were determined by C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI). Spinal pain and patient global health were assessed using horizontal visual analog scale. BMD was measured by dual-energy X-ray absorptiometry. There was a significant negative correlation of bone density T scores with acute-phase reactants (i.e., patients with lower T scores had higher level of CRP and ESR). That relationship was reflected more reliably at proximal femur sites than at the lumbar spine. There were also significant differences in ESR, BASDAI, BASFI, spinal pain and global health between three groups of patients according to WHO classification of osteoporosis (normal, osteopenic and osteoporotic). Significantly, more patients with osteopenia at the lumbar spine had lower BASDAI index than those with normal BMD ( P = 0.030). Our results indicate an association of low BMD with high disease activity in patients with AS. Femoral BMD seems to be more associated with disease activity and functional ability than lumbar spine BMD. [ABSTRACT FROM AUTHOR]
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- 2012
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24. Developments in therapies for spondyloarthritis.
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Sieper, Joachim
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SPONDYLOARTHROPATHIES , *NONSTEROIDAL anti-inflammatory agents , *PHYSICAL therapy , *CHEMICAL inhibitors , *TUMOR necrosis factors , *C-reactive protein , *THERAPEUTICS - Abstract
First-line therapy for spondyloarthritis (SPA) has not yet altered in the wake of new classification criteria; NSAIDs and physical therapy are recommended. Anti-TNF agents can be used when NSAIDs fail, but their efficacy has potentially been limited in previous trials by inclusion criteria requiring the presence of established, active disease. Now, not only patients with axial SpA (axSpA) with radiographic signs of sacroiliitis (that is, with ankylosing spondylitis), but also patients in whom structural damage is not--yet--visible radiographically (nonradiographic axSpA) can be included in trials of therapy for axSpA. TNF blockers, it seems already, are at least similarly effective in patients with non-radiographic axSpA as in those with established AS. Short symptom duration and a positive C-reactive protein test at baseline are currently the best predictors for a good response to TNF-blocking agents. Biologic agents besides anti-TNF therapies have so far failed in the treatment of axSpA. New bone formation seems currently to be best prevented by NSAIDs, not by TNF blockers. Whether earlier effective treatment of bony inflammation with anti-TNF therapy will be able to prevent ossification at a later stage has yet to be determined. New classification criteria for peripheral SpA will also allow treatment trials to be conducted more systematically than has previously been possible in this subgroup of patients. [ABSTRACT FROM AUTHOR]
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- 2012
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25. Referral strategies for early diagnosis of axial spondyloarthritis.
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Rudwaleit, Martin and Sieper, Joachim
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SPONDYLOARTHROPATHIES , *ANKYLOSING spondylitis , *THERAPEUTICS , *DIAGNOSIS , *RHEUMATOLOGISTS , *BACKACHE , *HLA-B27 antigen - Abstract
The spectrum of HLA-B27-associated inflammatory spine diseases is referred to as axial spondyloarthritis (axSpA). AxSpA encompasses established ankylosing spondylitis (AS) but also nonradiographic axSpA, and can be classified according to the Assessment of SpondyloArthritis international Society classification criteria for axSpA. Specific and effective therapy for axSpA includes education, physiotherapy, NSAIDs and biologic agents, as appropriate. Patients with axSpA, however, are often diagnosed late in the course of the disease. As specific therapy is available, the effective identification of those individuals who are likely to have axSpA among patients with chronic back pain in primary care and their subsequent referral to a rheumatologist for establishing a correct diagnosis is worth pursuing. Candidate referral parameters that can easily be applied to patients with chronic back pain and age at onset <45 years (the target population) include inflammatory back pain (IBP) and positivity for HLA-B27. Following diagnostic work-up by a rheumatologist, these referral parameters, either alone or in combination, have led to the diagnosis of as many as 33-45% of patients within this target population with axSpA, 41-62% of whom had undiagnosed AS. Thus, educating primary care physicians on the value of IBP and HLA-B27 testing within this target population, and referral to a rheumatologist if one of these parameters is positive, is a promising approach to reduce the long delay in diagnosing patients with axSpA. [ABSTRACT FROM AUTHOR]
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- 2012
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26. Impaired Peripheral Th1 CD4+ T Cell Response to Escherichia coli Proteins in Patients with Crohn's Disease and Ankylosing Spondylitis.
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Ergin, Asgar, Syrbe, Uta, Scheer, Rebecca, Thiel, Andreas, Adam, Thomas, Büssow, Konrad, Duchmann, Rainer, Zeitz, Martin, and Sieper, Joachim
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ESCHERICHIA coli diseases ,CROHN'S disease ,ANKYLOSING spondylitis ,BACTERIAL proteins ,T cells ,INFLAMMATORY bowel diseases ,IMMUNOREGULATION - Abstract
Background: To clarify the impact of T cell responses towards enteric antigens for chronic intestinal inflammation, we determined T helper 1 reactivity towards conserved Escherichia coli proteins in patients with Crohn's disease (CD) and healthy individuals and patients with ankylosing spondylitis (AS), who also often show microscopic inflammatory lesions within the gut or even develop overt inflammatory bowel disease. Methods: We determined the frequency of IFNγ+CD40L+ cells/CD4+ T cells after stimulation of whole blood with pools of E. coli proteins. Results: The E. coli-specific Th1 response was significantly reduced in CD patients and to a lower extent also in AS patients. Conclusions: E. coli is a target for polyclonal Th1 responses in healthy individuals. The impairment of these responses in CD and AS patients might be due to recruitment of enterobacteria-specific Th1 cells to the gut or might reflect inadequate priming of adaptive immune response. [ABSTRACT FROM AUTHOR]
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- 2011
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27. Blockade of intra-articular adrenergic receptors increases analgesic demands for pain relief after knee surgery.
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Kager, Ingo, Mousa, Shaaban A., Sieper, Joachim, Stein, Christoph, Pipam, W., and Likar, Rudolf
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ADRENERGIC receptors ,KNEE surgery ,OPIOID receptors ,IMMUNE response ,IMMUNE system - Abstract
Activation of opioid receptors on peripheral sensory nerve terminals by opioid peptides that are produced and released from immune cells can result in inhibition of inflammatory pain. This study tests the hypothesis that postoperative pain is attenuated endogenously through a local sympathetic neurotransmitter-activated release of opioids in patients undergoing knee surgery. We examined the expression of opioid peptides and adrenergic receptors in cells infiltrating inflamed synovial tissue and we hypothesized that intra-articular (i.a.) administration of the adrenergic receptor antagonist labetalol will increase postoperative analgesic consumption and/or pain intensity in these patients. In a double-blind, randomized manner, 75 patients undergoing therapeutic knee arthroscopy received i.a. placebo (20 ml saline) or labetalol (2.5 or 5 mg in 20 ml saline) at the end of surgery. Postoperative pain intensity was assessed by visual analog and verbal rating scales at rest and on exertion, and by the consumption of morphine via patient-controlled analgesia. Synovial biopsies were taken during the operation for double-immunofluorescence confocal microscopy studies. Alpha- and beta-adrenergic receptors were co-expressed in opioid peptide-containing cells. No significant difference was seen in pain scores, but patients receiving 2.5 mg labetalol requested significantly higher amounts of morphine. These findings are consistent with the notion that surgical stress induces sympathetically activated release of endogenous opioids from inflammatory cells and subsequent analgesia via activation of peripheral opioid receptors. [ABSTRACT FROM AUTHOR]
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- 2011
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28. Spondyloarthritis at the crossroads of imaging, pathology, and structural damage in the era of biologics.
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Appel, Heiner and Sieper, Joachim
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Ankylosing spondylitis (AS) is characterized by two key pathologic findings: sacroiliac joint and spinal inflammation and new bone formation with possible bone fusion, usually in the axial skeleton. Thus, structural damage in AS must be viewed differently than that in rheumatoid arthritis. Tumor necrosis factor blockers effectively inhibit inflammation, as shown by signs and symptoms, function, C-reactive protein, and MRI, and will probably prevent erosive structural damage. However, the ossification of already-damaged bone cannot be influenced by tumor necrosis factor blockade, because these drugs do not inhibit osteoblasts. It remains to be seen whether additional targeting of new bone formation is clinically meaningful in advanced AS. The most important action to prevent structural damage is probably an early diagnosis and effective anti-inflammatory treatment of AS. [ABSTRACT FROM AUTHOR]
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- 2008
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29. Diagnosing early ankylosing spondylitis.
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Song, In-Ho, Sieper, Joachim, and Rudwaleit, Martin
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Diagnosis of ankylosing spondylitis is still delayed by many years. Several efforts have been made in the past few years to shorten this delay. A new set of criteria for inflammatory back pain has performed better than previous sets. MRI has evolved to become the standard imaging modality for the detection of sacroiliitis during early disease, and it clearly outperforms quantitative scintigraphy, which was the standard screening test for many years. Promising new developments such as whole body MRI and ultrasound (sonography) for the detection of enthesitis or sacroiliitis deserve further evaluation. Serum antibodies directed against a 28-kD Drosophila antigen may provide additional diagnostic information. A recently proposed diagnostic algorithm in patients with suspected early ankylosing spondylitis may help physicians confidently diagnose patients before definite radiographic sacroiliitis is detectable. Finally, referral strategies for patients seen by primary care physicians seem to work well and are currently under further valuation. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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30. A case of axial undifferentiated spondyloarhritis diagnosis and management.
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Rudwaleit, Martin and Sieper, Joachim
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LUMBAR vertebrae , *BACKACHE , *MAGNETIC resonance imaging , *ERYTHROCYTES , *C-reactive protein , *LEUCOCYTES - Abstract
Background A 32-year-old white man presented with features of inflammatory back pain, including awakening at night and morning stiffness. He had acute back pain 4 years earlier as a result of a herniated lumbar disc. Investigations The orthopedic consultation included tests for neurologic deficits; a Lasegue test; a finger-to-floor distance test; X-rays of the lumbar spine; and MRI of the lumbar spine. The rheumatologic consultation included recordal of clinical history and family history; physical examination, including a Schober's test, lateral spine flexion, chest expansion, cervical rotation, and tragus-to-wall distance; blood tests, including genotyping for human leukocyte antigen B27 positivity, and measurements of C-reactive protein level and erythrocyte sedimentation rate; MRI of the sacroiliac joints with use of short tau inversion recovery sequences; and measurement of the Bath Ankylosing Spondylitis Disease Activity Index and the Bath Ankylosing Spondylitis Functional Index. [ABSTRACT FROM AUTHOR]
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- 2007
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31. Fluoroscopy-guided application of corticosteroids for local control of manubriosternal joint pain in patients with spondyloarthropathies.
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Golder, Werner, Karberg, Kirsten, and Sieper, Joachim
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SPONDYLOARTHROPATHIES ,CORTICOSTEROIDS ,FLUOROSCOPY ,JOINTS (Anatomy) ,SPINE diseases ,FLUORIMETRY - Abstract
Symptomatic manubriosternal arthritis, occasionally encountered with spondyloarthropathies, may not be adequately controlled by systemic therapy. Local corticosteroid injections make a potential contribution to symptomatic management. Three patients with acute inflammation of the joint as documented by MRI and fluoroscopy-guided therapy are presented. Topical treatment with triamcinolone acetonide (40 mg) was well tolerated and induced rapid and complete relief of pain for between 3 weeks and 3 months. In spite of the clinical improvement, the signs of inflammation in MRI did not decrease.Local steroid application seems to be an underused therapeutic modality in managing rheumatic involvement of the anterior chest wall. [ABSTRACT FROM AUTHOR]
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- 2004
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32. An elevated level of IL-10- and TGF?-secreting T cells, B cells and macrophages in the synovial membrane of patients with reactive arthritis compared to rheumatoid arthritis.
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Appel, Heiner, Neure, Lucia, Kuhne, Maren, Braun, Jürgen, Rudwaleit, Martin, and Sieper, Joachim
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INFECTIOUS arthritis ,INTERLEUKIN-10 ,TUMOR necrosis factors ,SYNOVIAL fluid ,B cells ,MACROPHAGES ,T cells - Abstract
A relative high secretion level of IL-10 and a low secretion of TNF-? has been described in the synovial fluid and peripheral blood of patients with reactive arthritis (ReA), possibly contributing to the persistence of bacteria. The role of TGF-? is less clear. We investigated these cytokines in the synovial membrane of patients with ReA and rheumatoid arthritis (RA) and tried to identify their cellular source. We used sections from the synovial membrane of 4 ReA and 4 RA patients which were double stained with immunofluorescence antibodies against cell surface markers for T cells (CD3), macrophages (CD68) and B cells (CD20) in combination with antibodies against intracellular cytokines TNF-?, IFN-?, TGF-?, IL-4 and IL-10, and quantified these using a fluorescence microscope. A lower number of TNF-?-secreting cells were found in ReA compared to RA: CD3+: 1.78±0.54% versus 5.02%±0.47% (p=0.034). CD68+: 2.86±0.52 versus 5.37±0.53% (p=0.034), CD20+ : 3.02±0.42% versus 3.58±0.48% (p>0.05). A higher number of IL-10 positive cells were found in ReA compared to RA: CD3+: 3.27±1.5% versus 1.13±0.50% (p=0.034), CD68+ 1.23±0.75% versus 0.83±0.35%(p>0.05), CD20+: 3.70±1.6% versus 1.6±1.1% (p>0.05). A difference between ReA and RA was also found for TGF-?+ T cells: CD3+ 7.86+1.5% versus 1.78+0.35% (p= 0.032); CD20+: 7.91+2.1% versus 2.1+2.8% (p>0.05), CD68+: 7.81%+1.24% versus 2.12+0.28% (p= 0.032). In conclusion, we saw a different cytokine secretion pattern in the synovial membrane of ReA and RA. For T cells in ReA we found a cytokine secretion profile typical for T regulatory cells 1 (Tr1), with an elevated level of IL-10- and TGF-?-secreting cells. Whether this is due to a more general difference in TNF-?, IL-10 or TGF-? production which is genetically determined or regulated by T cells remains to be determined. [ABSTRACT FROM AUTHOR]
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- 2004
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33. Disease mechanisms in reactive arthritis.
- Author
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Sieper, Joachim
- Abstract
Reactive arthritis (ReA) occurs after a preceding bacterial infection of the urogenital or gastroenteral tract. The bacteria triggering ReA persist in vivo and seem to be responsible for triggering an immune response. A cytokine imbalance with a relative lack of T-helper 1 cytokines may play an important role allowing these bacteria to survive. This seems to be relevant for manifestation and chronicity of the arthritis. For the chronic cases and cases evolving into ankylosing spondylitis, the interaction between bacteria and human leukocyte antigen B27 plays an additional crucial role. Among others, the arthritogenic peptide hypothesis is one way to explain this association. Human leukocyte antigen B27-restricted peptides from Yersinia and Chlamydia, which are stimulatory for CD8+ T cells derived from patients with ReA, have been identified. The exact role of such peptides for the pathogenesis of ReA and other spondyloarthritides still has to be defined. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
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34. Role of Novel Biological Therapies in Psoriatic Arthritis: Effects on Joints and Skin.
- Author
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Braun, Juergen and Sieper, Joachim
- Subjects
- *
PSORIATIC arthritis , *THERAPEUTICS - Abstract
Psoriatic arthritis (PsA) is a partly debilitating disease that may affect small and large joints and the spine. Patients with PsA are divided into different subgroups according to joint involvement and their disease may be classified as part of the spectrum of spondyloarthritides or seronegative rheumatoid arthritis. Traditional treatment comprises nonsteroidal anti-inflammatory drugs, systemic and intra-articular corticosteroids and disease-modifying antirheumatic drugs such as sulfasalazine, methotrexate and cyclosporin. On the basis of the very recent studies performed in the US and Germany, patients with severe disease can be treated with anti-tumour necrosis factor (TNF) therapy. Biologicals such as etanercept and infliximab have been used successfully to treat PsA. While etanercept is a 75kD TNF receptor fusion protein that binds to TNFα and TNFβ, infliximab is a chimeric monoclonal antibody that binds to TNFα both in its soluble form in the serum and on the cell membrane. Adalimumab is a fully humanised antibody recognising TNFα that has not been tested in PsA to date. Another biological agent, alefacept, is directed against the adhesion molecule lymphocyte function-associated antigen (LFA)-2, which is known to interfere with T-cell activation. Alefacept has been shown to be efficacious in a limited number of patients with PsA. Taken together, there has been definite recent progress in the treatment of PsA. Severely affected patients may especially have substantial benefit from therapy with biologicals directed against TNFα and other targets. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
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35. Pathogenesis of reactive arthritis.
- Author
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Sieper, Joachim
- Abstract
There is good evidence that bacteria persist in vivo in patients with reactive arthritis (ReA). While Chlamydia seem to hide inside the joint, other areas such as gut mucosa or lymph nodes seem to be more likely places for Salmonella and Yersinia. T-helper (Th) 1 cells secreting cytokines such as IFNg and TNFa are crucial for an effective elimination of these bacteria. An inhibited Th1-response could be demonstrated in ReA, probably contributing to bacterial persistence. While HLA-B27 is found in only approximately 50% of patients with acute ReA, HLA-B27 seems to be crucial for the development of features typical with chronic spondyloarthropathy, such as sacroiliitis. Among several hypotheses to explain the interaction of bacteria with HLA-B27, the most likely seems to be that until now unknown bacterial or selfantigens were presented by HLA-B27 to CD8+ T-cells. An important site where the immunopathology takes place seems to be at the insertion of tendons and ligaments at bone. Because antibiotics have failed so far in the treatment of ReA immunomodulatory therapies, based on a better understanding of the pathogenesis, alone or in combination with antibiotics might be an option for the future. [ABSTRACT FROM AUTHOR]
- Published
- 2001
- Full Text
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36. Introduction.
- Author
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Sieper, Joachim and Braun, Jürgen
- Abstract
Only slightly more common in men than in women, ankylosing spondylitis (AS) is a chronic inflammatory disease which, probably as a result of an autoimmune response, causes inflammation in the sacroiliac joints, vertebrae and adjacent joints. Patients also frequently have inflammation of an enthesis (insertion of a tendon or ligament into the bone), the peripheral joints and the eye; the lungs, heart valves and kidneys are only rarely affected. The onset of symptoms – notably back pain and stiffness – is normally already noticeable in adolescence or early adulthood. Eventually, AS can cause the vertebrae to fuse together, with obvious adverse impact on patient mobility and function. To date, the disease has no cure, but drug and physical therapy can improve pain, inflammation and other symptoms considerably; indeed, even remission is now a realistic goal. A major breakthrough in the treatment of this disease was the demonstration of the high efficacy of the tumour necrosis factor (TNF)–blocking agents [1]. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
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37. Cytokines and the immunopathology of the spondyloarthropathies.
- Author
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Braun, Jürgen and Sieper, Joachim
- Abstract
In contrast to rheumatoid arthritis (RA), the triggering antigens are known in reactive arthritis (ReA) and Lyme arthritis. Thus, in these arthritides the antigen-specific T-cell response can be investigated in much detail and lessons possibly learned for other spondyloarthropathies (SpA) such as ankylosing spondylitis (AS) where T cells may well also play an important role in the pathogenesis. This article focusses on the immunopathology of the SpA, ReA, and AS with special reference to T cells and cytokines. [ABSTRACT FROM AUTHOR]
- Published
- 1999
- Full Text
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38. Basic therapy in the treatment of arthritis.
- Author
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Sieper, Joachim
- Published
- 1998
- Full Text
- View/download PDF
39. Psoriatische Onycho-Pachydermo- Periostitis (POPP).
- Author
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Schröder, Kathrin, Goerdt, Sergij, Sieper, Joachim, Krasagakis, Konstantinos, Almond-Roesler, Brigitte, and Orfanos, Constantin E.
- Abstract
Copyright of Der Hautarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 1997
- Full Text
- View/download PDF
40. Spondyloarthropathies in 2010: new insights into therapy-TNF blockade and beyond.
- Author
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Sieper, Joachim
- Subjects
- *
SPONDYLOARTHROPATHIES , *ANKYLOSIS , *JOINT diseases , *TUMOR necrosis factors , *ETANERCEPT ,SACROILIAC joint diseases - Abstract
The article highlights the 2010 research findings in the field of spondyloarthropathies. It discusses the researches conducted by S. Urderhardt, M. Dougados and J. D. Carter. The article also enumerates 2010 key advances, namely, findings that blockade of DKK1 is crucial for ankylosis of the sacroiliac joints, that the tumor necrosis factor (TNF) inhibitor etanercept is effective for the treatment of heel enthesitis and that combination antibiotic treatment can successfully treat chronic Chlamydia-induced spondyloarthritis (SpA).
- Published
- 2011
- Full Text
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41. Treatment of Axial Spondyloarthritis: What Does the Future Hold?
- Author
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Poddubnyy, Denis and Sieper, Joachim
- Abstract
Purpose of Review: To provide a summary of the recent and expected developments related to the treatment of axial spondyloarthritis. Recent Findings: An increasing number of interleukin-17 blocking agents show efficacy in axial spondyloarthritis including both non-radiographic and radiographic forms. Janus kinase inhibitors showed promising results in phase II studies in radiographic axial spondyloarthritis and have, therefore, a potential to become a therapeutic option in this indication in the future. Inhibition of structural damage progression in axial spondyloarthritis seems to be possible in the case of effective and early anti-inflammatory treatment, although there are still open questions related to particular drug classes. Summary: Despite major advances in the field and growing therapeutic options, there are still many open questions related to the optimized treatment strategies and to the individual choice of a drug in axial spondyloarthritis. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
42. Antibiotika in der Behandlung von Arthritiden.
- Author
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Sieper, Joachim
- Abstract
Copyright of Der Orthopäde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 1998
- Full Text
- View/download PDF
43. Current Unmet Needs in Spondyloarthritis.
- Author
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Poddubnyy, Denis and Sieper, Joachim
- Abstract
Purpose of Review: There was a substantial progress in the field of spondyloarthritis (SpA) in terms of understanding disease mechanisms, early diagnosis, and improved treatment. Nonetheless, several unresolved questions and unmet needs do remain. Recent Findings: Although the diagnostic delay in axial SpA is decreasing, it remains one of the longest in rheumatology. Application of referral strategies, as well as correct application and interpretation of imaging finding in the clinical context, is the main key to early diagnosis of axial SpA. Tumor necrosis factor (TNF) alpha and interleukin (IL)-17 represent currently two major treatment targets in SpA, while other promising targets such as IL-23 or IL-6 failed in clinical trials. There is an unmet need for strategy trials to optimize and to individualize treatment in SpA. The role of Janus kinases and their blockade in SpA is still to be explored. TNF blockade showed efficacy in peripheral SpA, and other targets (IL-17 and IL-23) should be investigated in clinical trials. Early, effective, and long-term suppression of inflammation is currently the best method to prevent structural damage progression in the spine in axial SpA, while specific effects of IL-17 blockade and of nonsteroidal anti-inflammatory drugs on new bone formation are still being investigated. Summary: This review summarizes the recent advances in diagnosis and treatment of SpA and discusses the current unmet needs in the field. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
44. Socioeconomic aspects of ankylosing spondylitis.
- Author
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Sieper, Joachim and Braun, Jürgen
- Abstract
Mainly as a result of the high costs for Mainly as a result of the high costs for (TNF) blockers the analysis of socioeconomic data for ankylosing spondylitis, as for other chronic diseases, has become of great interest. In these kinds of analyses direct and indirect costs caused by the disease are balanced against treatment costs, savings of direct and indirect costs, and gain in quality of life. Quality of life has been found to be equally reduced in patients with ankylosing spondylitis and in patients with rheumatoid arthritis, but healthcare costs were higher in rheumatoid arthritis [40]. An effort has been made to calculate the cost–effectiveness of the TNF–blocking agents infliximab and etanercept in the treatment of ankylosing spondylitis [102, 103]. Such a treatment seems to be cost–effective when the reduction of direct and indirect costs and the gain in quality of life are calculated against the drug costs, especially in patients with high disease activity and good response to treatment. However, future research is necessary to learn more about the natural course of the disease, prognostic factors and long–term effects of the treatment with TNF–blocking agents. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
45. Etanercept A Viewpoint by Joachim Sieper.
- Author
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Sieper, Joachim
- Subjects
- *
ETANERCEPT , *ANKYLOSING spondylitis , *THERAPEUTICS , *CLINICAL trials , *PLACEBOS , *NONSTEROIDAL anti-inflammatory agents , *PHYSICAL therapy , *TUMOR necrosis factors - Abstract
Comments on the use of etanercept for the treatment of ankylosing spondylitis. Improvement in disease activity achieved by using etanercept shown by several placebo-controlled studies; Use of nonsteroidal anti-inflammatory agents and physiotherapy in treating the disease; Need for further studies to answer the question whether rumor necrosis factor-blockers currently available for AS differ in efficacy and tolerability.
- Published
- 2004
- Full Text
- View/download PDF
46. Relevance of osteoproliferation as an outcome parameter in ankylosing spondylitis.
- Author
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Appel, Heiner, Rudwaleit, Martin, and Sieper, Joachim
- Subjects
- *
ANKYLOSING spondylitis , *ANKYLOSIS , *SPONDYLITIS , *BONES , *MUSCULOSKELETAL system - Abstract
The article reports on osteoproliferation and ankylosing spondylitis (AS). It mentions that AS affects more males than females and can affect the spine and joints. Inflammation and new bone formation occurs in AS. The Stoke Ankylosing Spondylitis is used for scoring the radiographic progression of the spine. An overview of the role of osteoproliferation in ankylosing spondylitis is included.
- Published
- 2008
- Full Text
- View/download PDF
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