Joachim Sieper

Publications (127)686.91 Total impact

• Article: Radiographic progression in ankylosing spondylitis/axial spondyloarthritis: how fast and how clinically meaningful?

  Denis Poddubnyy, Joachim Sieper
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  ABSTRACT: Radiographic progression in the axial skeleton is considered as an important outcome in ankylosing spondylitis (AS) and in the whole group of axial spondyloarthritis (SpA). Recently new data on the rates and predictors of radiographic progression from observational cohorts have become available. Here we summarize recent data and discuss their clinical relevance and directions for further investigations. Nonradiographic axial SpA progresses to AS with a rate of about 12% over 2 years; elevated C-reactive protein (CRP) is an important predictor of such a progression. The rate of radiographic progression in the spine is strongly dependent on the presence of the following risk factors: syndesmophytes at baseline, elevated acute phase reactants (CRP and/or erythrocyte sedimentation rate) and smoking. The presence of radiographic damage in the spine has a strong impact on spinal mobility and functional status, although the association of radiographic sacroiliitis progression with the functional status remains unclear. Radiographic progression in the spine and, to a lesser extent, in the sacroiliac joint represents a clinically relevant clinical outcome and treatment target in AS/axial SpA.
  Current opinion in rheumatology 04/2012; 24(4):363-9. · 4.60 Impact Factor
• Article: Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort.

  Denis Poddubnyy, Martin Rudwaleit, Hildrun Haibel, Joachim Listing, Elisabeth Märker-Hermann, Henning Zeidler, Jürgen Braun, Joachim Sieper
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  ABSTRACT: To investigate the influence of non-steroidal anti-inflammatory drugs (NSAIDs) intake on radiographic spinal progression over 2 years in patients with ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (SpA). 164 patients with axial SpA (88 with AS and 76 with non-radiographic axial SpA) were selected for this analysis based on availability of spinal radiographs at baseline and after 2 years of follow-up and the data on NSAIDs intake. Spinal radiographs were scored by two trained readers in a concealed randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system. An index of the NSAID intake counting both dose and duration of drug intake was calculated. High NSAIDs intake (NSAID index≥50) in AS was associated with lower likelihood of significant radiographic progression defined as an mSASSS worsening by ≥2 units: OR=0.15, 95% CI 0.02 to 0.96, p=0.045 (adjusted for baseline structural damage, elevated C reactive protein (CRP) and smoking status) in comparison with patients with low NSAIDs intake (NSAID index<50). This effect was most pronounced in patients with baseline syndesmophytes plus elevated CRP: mean mSASSS progression was 4.36±4.53 in patients with low NSAIDs intake versus 0.14±1.80 with high intake, p=0.02. In non-radiographic axial SpA, no significant differences regarding radiographic progression between patients with high and low NSAIDs intake were found. A high NSAIDs intake over 2 years is associated with retarded radiographic spinal progression in AS. In non-radiographic axial SpA this effect is less evident, probably due to a low grade of new bone formation in the spine at this stage.
  Annals of the rheumatic diseases 03/2012; 71(10):1616-22. · 8.11 Impact Factor
• Article: Frequency and duration of drug-free remission after 1 year of treatment with etanercept versus sulfasalazine in early axial spondyloarthritis: 2 year data of the ESTHER trial.

  In-Ho Song, Christian E Althoff, Hildrun Haibel, Kay-Geert A Hermann, Denis Poddubnyy, Joachim Listing, Anja Weiß, Svetlana Djacenko, Gerd R Burmester, Martin Bohl-Bühler, Bruce Freundlich, Martin Rudwaleit, Joachim Sieper
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  ABSTRACT: The aims of this study were (1) to assess the frequency and duration of drug-free remission and efficacy of etanercept (ETA) treatment after flare in patients with early active axial spondyloarthritis who were treated with ETA (n=40) versus sulfasalazine (SSZ, n=36) for 48 weeks and (2) to analyse the efficacy of ETA treatment in patients in year 2 who did not reach remission at week 48. At week 48, patients who reached study remission (Assessment of Spondyloarthritis international Society (ASAS) plus MRI remission) were followed up without active treatment up to 1 year. In case of a flare, patients were treated with ETA for another year. All patients who were not in ASAS plus MRI remission at week 48 were treated with ETA in year 2. ASAS plus MRI remission at week 48 was reached significantly more often in ETA-treated compared to SSZ-treated patients (33% vs 11%, p=0.03). However, the flare rate was not different between these two groups: 69% in the ETA group versus 75% in the SSZ group. Only 8% of patients initially treated with ETA versus 3% of those initially treated with SSZ reached permanent drug-free remission (not significant). After treatment with ETA over 1 year, patients with flare showed an improvement in all clinical and imaging variables. Patients with axial spondyloarthritis treated with ETA over 1 year did not reach drug-free remission in a higher percentage compared to patients from a control group treated with SSZ.
  Annals of the rheumatic diseases 03/2012; 71(7):1212-5. · 8.11 Impact Factor
• Article: The risks of smoking in patients with spondyloarthritides.

  Jürgen Braun, Joachim Sieper, Angela Zink
  Annals of the rheumatic diseases 02/2012; 71(6):791-2. · 8.11 Impact Factor
• Article: ASAS recommendations for variables to be collected in clinical trials/epidemiological studies of spondyloarthritis.

  Maxime Dougados, Jurgen Braun, Rubén Burgos Vargas, Laure Gossec, Walter Maksymowych, Joachim Sieper, Désirée van der Heijde
  Annals of the rheumatic diseases 01/2012; 71(6):1103-4. · 8.11 Impact Factor
• Article: High level of functional dickkopf-1 predicts protection from syndesmophyte formation in patients with ankylosing spondylitis.

  Gisela Ruiz Heiland, Heiner Appel, Denis Poddubnyy, Jochen Zwerina, Axel Hueber, Hildrun Haibel, Xenofon Baraliakos, Joachim Listing, Martin Rudwaleit, Georg Schett, Joachim Sieper
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  ABSTRACT: The molecular mechanisms of syndesmophyte formation in ankylosing spondylitis (AS) are yet to be characterised. Molecules involved in bone formation such as Wnt proteins and their antagonists probably drive syndesmophyte formation in AS. This study investigated sequential serum levels of functional dickkopf-1 (Dkk1), a potent Wnt antagonist involved in bone formation in arthritis, by capture ELISA with its receptor LRP6 in 65 AS patients from the German Spondyloarthritis Inception Cohort. Dkk1 levels were then related to structural progression (syndesmophyte formation) as well as sclerostin and C-reactive protein (CRP) levels. Functional Dkk1 levels were significantly (p=0.025) higher in patients with no syndesmophyte growth (6.78 ± 5.48 pg/ml) compared with those with syndesmophyte growth (4.13 ± 2.10 pg/ml). Dkk1 levels were highly correlated to serum sclerostin levels (r=0.71, 95% CI 0.53 to 0.82; p<0.001) but not to CRP (r=0.15, 95% CI -0.10 to 0.38; p=0.23). AS patients with no syndesmophyte formation show significantly higher functional Dkk1 levels suggesting that blunted Wnt signalling suppresses new bone formation and consequently syndesmophyte growth and spinal ankylosis. Similar to serum sclerostin levels, the functional Dkk1 level thus emerges as a potential biomarker for structural progression in patients with AS.
  Annals of the rheumatic diseases 12/2011; 71(4):572-4. · 8.11 Impact Factor
• Article: Evaluation of the spinal pain score in AS--a psychometric analysis.

  In-Ho Song, Hildrun Haibel, Elke S Stelling, Joachim Sieper, Martin Rudwaleit
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  ABSTRACT: Objective. To evaluate the spinal pain score (SpiPS), a semi-objective instrument for measuring disease activity in AS.Methods. The SpiPS is based on the physical examination of the spine and was evaluated according to the outcome measures in rheumatology filter in 659 AS patients from different cohorts including two interventional trials. Aspects of truth, discrimination and feasibility were assessed.Results. The SpiPS significantly distinguished between patients with high and low disease activity. The correlation of the SpiPS with the disease activity index BASDAI was relatively weak in the entire cohort of AS patients (r = 0.36) but moderate to good in AS patients with short disease duration (r = 0.66). Correlations with the functional index BASFI (r = 0.38), patient global (r = 0.18), physician global (r = 0.51) and BASMI (r = 0.36) were weak to moderate in the entire cohort. Logistic regression revealed SpiPS and patient global to be independently associated with disease activity (BASDAI) after adjustments for age, gender, disease duration, CRP and HLA-B27. Sensitivity to change expressed as effect size (ES) was 0.82 and 1.58, respectively, and highly comparable with that of BASDAI in the two interventional trials. Reproducibility of the SpiPS was good (intra-observer variability r = 0.93, inter-observer variability r = 0.79).Conclusion. The SpiPS is a measure of disease activity in AS and is sensitive to change. However, disease domains other than disease activity are also captured by the SpiPS, and our analysis failed to demonstrate any additional value of the SpiPS over existing instruments.
  Rheumatology (Oxford, England) 12/2011; · 4.24 Impact Factor
• Source

  Available from: PubMed Central

  Article: Early response to adalimumab predicts long-term remission through 5 years of treatment in patients with ankylosing spondylitis.

  Joachim Sieper, Désirée van der Heijde, Maxime Dougados, L Steve Brown, Frederic Lavie, Aileen L Pangan
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  ABSTRACT: To describe the efficacy and safety through 5 years of adalimumab treatment in patients with ankylosing spondylitis (AS), and to identify predictors of remission. Patients with active AS were followed up to 5 years during a 24-week randomised, controlled period, followed by an open-label extension. Disease activity and clinical improvement were evaluated by Assessment in Spondyloarthritis International Society (ASAS) responses, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Kaplan-Meier was used to identify patients with sustained ASAS partial remission (PR) or ASDAS inactive disease (ID) for three or more consecutive visits spanning ≥ 6 months. Logistic regression was used to identify factors associated with remission. Explanatory variables included baseline demographic and disease characteristics and week 12 responses. Of the 311 patients who received at least one dose of adalimumab, 202 (65%) completed the 5-year study. Among 125 patients who received 5 years of adalimumab, 70%, 77%, 51% and 61% achieved ASAS40, BASDAI 50, ASAS PR and ASDAS ID, respectively. Of 311 adalimumab-treated patients, 45% and 55% achieved sustained ASAS PR and ASDAS ID at any time during study participation. The strongest predictor of remission at years 1 and 5 and of sustained remission was achieving remission at 12 weeks of treatment; baseline characteristics showed weaker associations. Adverse events were comparable with previous reports on adalimumab safety. In patients with active AS, the efficacy and safety of adalimumab were maintained through 5 years with about half of the patients experiencing sustained remission at any time during the study. Early achievement of remission was the best predictor of long-term and sustained remission.
  Annals of the rheumatic diseases 11/2011; 71(5):700-6. · 8.11 Impact Factor
• Source

  Available from: Denis Poddubnyy

  Article: Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondylarthritis.

  Denis Poddubnyy, Hildrun Haibel, Joachim Listing, Elisabeth Märker-Hermann, Henning Zeidler, Jürgen Braun, Joachim Sieper, Martin Rudwaleit
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  ABSTRACT: To assess prospectively the rates and to explore predictors of spinal radiographic progression over 2 years in a cohort of patients with early axial spondylarthritis (SpA). Two hundred ten patients with axial SpA from the German Spondyloarthritis Inception Cohort were selected for this analysis based on the availability of radiographs at baseline and after 2 years of followup. Spinal radiographs were scored by 2 trained readers in a blinded, randomly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Spinal radiographic progression was defined as worsening of the mean mSASSS by ≥2 units over 2 years. Among the patients with axial SpA, 14.3% showed spinal radiographic progression after 2 years (20% of those with AS and 7.4% of those with nonradiographic axial SpA). The following parameters were independently associated with spinal radiographic progression: presence of syndesmophytes at baseline (odds ratio [OR] 6.29, P < 0.001), elevated levels of markers of systemic inflammation (for the erythrocyte sedimentation rate, OR 4.04, P = 0.001; for C-reactive protein level time-averaged over 2 years, OR 3.81, P = 0.001), and cigarette smoking (OR 2.75, P = 0.012). These associations were confirmed by multivariate logistic regression analysis. No clear association with spinal radiographic progression was observed for HLA-B27 status, sex, age, disease duration, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, presence of peripheral arthritis, enthesitis, psoriasis, treatment with nonsteroidal antiinflammatory drugs, or treatment with disease-modifying antirheumatic drugs at baseline. The presence of radiographic damage at baseline (syndesmophytes), elevated levels of acute-phase reactants, and cigarette smoking were all independently associated with spinal radiographic progression in patients with early axial SpA.
  Arthritis & Rheumatism 11/2011; 64(5):1388-98. · 7.87 Impact Factor
• Chapter: Imaging in ankylosing spondylitis

  Joachim Sieper, Jürgen Braun
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  ABSTRACT: 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.
  10/2011: pages 39-48;
• Source

  Available from: newbooks-services.de

  Chapter: Overview of ankylosing spondylitis

  Joachim Sieper, Jürgen Braun
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  ABSTRACT: 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).
  10/2011: pages 5-12;
• Article: Synovial and peripheral blood CD4+FoxP3+ T cells in spondyloarthritis.

  Heiner Appel, Peihua Wu, Rebecca Scheer, Claudia Kedor, Birgit Sawitzki, Andreas Thiel, Andreas Radbruch, Joachim Sieper, Uta Syrbe
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  ABSTRACT: Regulatory T cells are characterized by expression of the transcription factor FoxP3 and are thought to be involved in the pathogenesis of autoimmune diseases. We determined the frequency and phenotypic characteristics of CD4+FoxP3+ T cells in the blood and synovial fluid (SF) of patients with inflammatory joint diseases. SF from 10 patients with ankylosing spondylitis (AS), 20 patients with other spondyloarthritides or with peripheral arthritis (pSpA), and 12 patients with rheumatoid arthritis (RA), and peripheral blood (PB) from 22 patients with AS, 19 with pSpA, 15 with RA, and 12 healthy controls were stained for CD4, FoxP3, CD25, and CD127 and different effector cytokines and then analyzed by flow cytometry. Methylation pattern of the Treg-specific demethylated region (TSDR) was determined after bisulfite treatment by quantitative polymerase chain reaction. In all groups of patients we observed higher frequencies of Foxp3+ cells/CD4+ T cells within SF compared to PB. The frequency of synovial Foxp3+ cells/CD4+ T cells was significantly higher in patients with pSpA (18.79% ± 6.41%) compared to patients with AS (9.69% ± 4.11%) and patients with RA (5.95% ± 2.21%). CD4+FoxP3+ T cells were CD25+ and CD127- and lacked effector cytokine production in any of the different patient groups. The majority of the CD4+CD25+CD127- T cells showed demethylation of the TSDR within the Foxp3 locus, confirming its regulatory phenotype. Our data show accumulation of Foxp3+ T cells within inflamed joints. These Foxp3+ T cells are mainly of stable T regulatory phenotype. The high frequency of Foxp3+ T cells in pSpA might contribute to the spontaneous resolution and remitting course of arthritis in pSpA as compared to the more persistent joint inflammation in RA.
  The Journal of Rheumatology 09/2011; 38(11):2445-51. · 3.69 Impact Factor
• Article: Evaluation of 2 screening strategies for early identification of patients with axial spondyloarthritis in primary care.

  Denis Poddubnyy, Janis Vahldiek, Inge Spiller, Beate Buss, Joachim Listing, Martin Rudwaleit, Joachim Sieper
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  ABSTRACT: To evaluate 2 referral strategies for axial spondyloarthritis (SpA) in patients with chronic low back pain at the primary care level. Referral physicians (n = 259) were randomly assigned to either Strategy 1 or Strategy 2 in order to refer patients with chronic back pain (duration > 3 months), age at onset of back pain < 45 years, and no diagnosis of axial SpA, to a cooperating rheumatologist (n = 43). According to Strategy 1, suitable patients were referred if at least 1 of the following screening criteria was present: inflammatory back pain, HLA-B27, or sacroiliitis detected by imaging. According to Strategy 2, patients were referred if 2 out of 5 criteria were positive: the same 3 criteria from Strategy 1 and additionally a positive family history of ankylosing spondylitis (AS) or a good treatment response to nonsteroidal antiinflammatory drugs. The final diagnosis of the rheumatologist was used as the "gold standard." In total, 560 consecutively referred patients were included in the analysis. Among 318 patients referred by Strategy 1, 41.8% (95% CI 36.5%-47.3%) were diagnosed with definite axial SpA. Among 242 patients referred by the second strategy, definite axial SpA was diagnosed in 36.8% (95% CI 31.0%-43.0%) of the cases. Both referral strategies demonstrated comparable performance in identification of patients with axial SpA. Strategy 1 might be preferred as an easy and reliable screening method for axial SpA at the primary care level.
  The Journal of Rheumatology 09/2011; 38(11):2452-60. · 3.69 Impact Factor
• Article: Impaired peripheral Th1 CD4+ T cell response to Escherichia coli proteins in patients with Crohn's disease and ankylosing spondylitis.

  Asgar Ergin, Uta Syrbe, Rebecca Scheer, Andreas Thiel, Thomas Adam, Konrad Büssow, Rainer Duchmann, Martin Zeitz, Joachim Sieper
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  ABSTRACT: 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. We determined the frequency of IFNγ+CD40L+ cells/CD4+ T cells after stimulation of whole blood with pools of E. coli proteins. The E. coli-specific Th1 response was significantly reduced in CD patients and to a lower extent also in AS patients. 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.
  Journal of Clinical Immunology 09/2011; 31(6):998-1009. · 3.08 Impact Factor
• Article: Relation of HLA-B27, tumor necrosis factor-α promoter gene polymorphisms, and T cell cytokine production in ankylosing spondylitis -- a comprehensive genotype-phenotype analysis from an observational cohort.

  Denis A Poddubnyy, Elisabeth Märker-Hermann, Wiebke Kaluza-Schilling, Henning Zeidler, Jurgen Braun, Joachim Listing, Joachim Sieper, Martin Rudwaleit
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  ABSTRACT: In a pilot study, a distinct T cell cytokine pattern associated with HLA-B27 status and a tumor necrosis factor-α (TNF-α) promoter gene polymorphism was found at -308 (TNF-308). The objective of our study was to assess these associations in a different cohort of patients with ankylosing spondylitis (AS) and to evaluate any effect on clinical measurements. Peripheral T cell cytokine production of patients with AS (n = 121) from the German Spondyloarthritis Inception Cohort was assessed by flow cytometry and correlated with HLA-B27, TNF-238, and TNF-308, and with clinical measurements. In HLA-B27-positive, anti-TNF-naive patients with AS, the percentages of TNF-α-producing (5.02%) and interleukin 10-producing (0.31%) CD8+ cells were significantly lower in comparison to HLA-B27-negative patients (9.52%, p = 0.048, and 0.46%, p = 0.037, respectively). A nonsignificant trend was found for a lower production of TNF-α by CD4+ and interferon-γ by both CD4+ and CD8+ T cells, as compared to HLA-B27-negative patients with AS (p > 0.05 for all comparisons). The A allele at TNF-308 was associated with a lower percentage of TNF-α-producing CD4+ T cells. No significant correlations were found between clinical or radiological measurements and cytokine production or with TNF-α promoter gene polymorphisms. Modulation of T cell cytokines by HLA-B27 might play a role in AS pathogenesis in B27-positive individuals. No conclusive data were obtained for the TNF-308 polymorphism on cytokine production, and no effect of cytokines or genetic polymorphisms on clinical manifestations was observed.
  The Journal of Rheumatology 09/2011; 38(11):2436-41. · 3.69 Impact Factor
• Source

  Available from: Peihua Wu

  Article: Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.

  Heiner Appel, René Maier, Peihua Wu, Rebecca Scheer, Axel Hempfing, Ralph Kayser, Andreas Thiel, Andreas Radbruch, Christoph Loddenkemper, Joachim Sieper
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  ABSTRACT: In this study, we analysed the number of IL-17(+) cells in facet joints, in the peripheral blood (PB) and synovial fluid (SF) of spondyloarthritis (SpA) patients and compared these results with those of patients with other rheumatic diseases and controls. Immunohistochemical analysis of IL-17(+) cells was performed in facet joints of 33 ankylosing spondylitis (AS) patients and compared with data from 20 osteoarthritis (OA) patients. The frequency of IL-17(+)CD4(+) T cells in PB and SF of SpA patients (PB n = 30, SF n = 11), rheumatoid arthritis (RA) patients (PB n = 14, SF n = 7), OA patients (PB n = 10) and healthy controls (PB n = 12) was analysed after stimulation with Staphylococcus aureus Enterotoxin B and phorbol 12-myristate 13-acetate/ionomycin and quantified by flow cytometry. In AS facet joints, the frequency of IL-17-secreting cells was significantly higher than in samples obtained from OA patients (P < 0.001), with a slight predominance of IL-17(+) cells among the mononuclear cells (61.5% ± 14.9%) compared to cells with polysegmental nuclei. Immunofluorescence microscopy revealed that the majority of IL-17(+) cells were myeloperoxidase-positive (35.84 ± 13.06/high-power field (HPF) and CD15(+) neutrophils (24.25 ± 10.36/HPF), while CD3(+) T cells (0.51 ± 0.49/HPF) and AA-1(+) mast cells (2.28 ± 1.96/HPF) were less often IL-17-positive. The frequency of IL-17(+)CD4(+) T cells in the PB and SF of SpA patients did not differ significantly compared to RA patients, OA patients or healthy controls. Our data suggest an important role for IL-17 in the inflammatory processes in AS. However, the innate immune pathway might be of greater relevance than the Th17-mediated adaptive immune response.
  Arthritis research & therapy 06/2011; 13(3):R95. · 4.27 Impact Factor
• Article: Persistent clinical efficacy and safety of infliximab in ankylosing spondylitis after 8 years--early clinical response predicts long-term outcome.

  Xenofon Baraliakos, Joachim Listing, Claudia Fritz, Hildrun Haibel, Rieke Alten, Gerd-Rüdiger Burmester, Andreas Krause, Stefan Schewe, Matthias Schneider, Helmut Sörensen, Reinhold Schmidt, Joachim Sieper, Juergen Braun
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  ABSTRACT: To report for the first time on the efficacy and safety of anti-TNF therapy after 8 years of follow-up in patients with active AS, and analyse possible short-term predictors for long-term clinical outcomes. In this open-label extension of a randomized controlled trial, proportions of the initially included 69 patients with active AS were treated with infliximab 5 mg/kg i.v./6 weeks for 8 years. The last report was published after 5 years. All analyses were based on completers. Overall, 33 (48%) patients completed 8 years. Their mean (s.d.) BASDAI [2.6 (1.9)], BASFI [3.3 (2.6)] and BASMI [2.7 (2.4)] remained low at Year 8. At the end of Year 8, most patients were either in partial remission (n = 8, 24%) or had low disease activity (BASDAI < 3; n = 21, 64%). No new serious adverse events occurred within the past 3 years. Adverse events were the most frequent reason for dropout (56%). There were no differences between completers and dropouts at baseline, but the latter had higher BASFI values at dropout. No baseline parameter was associated with good long-term response to infliximab, but lower BASDAI levels after 12 weeks were predictive of a higher probability of partial remission [odds ratio (OR) 2.9, 95% CI 1.3, 6.3, P = 0.007], low disease activity (OR 1.7, 95% CI 1.2, 2.3, P = 0.005) or remaining on treatment (OR 0.79, 95% CI 0.61, 1.01, P = 0.06) after 8 years. Almost half of the initially treated patients remained on anti-TNF therapy for 8 years, and almost 90% were in partial remission or had low disease activity. Short-term response (low BASDAI at 3 months) is predictive of outcome after 8 years. Infliximab therapy was safe over 8 years.
  Rheumatology (Oxford, England) 06/2011; 50(9):1690-9. · 4.24 Impact Factor
• Article: 2010 Update of the international ASAS recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis.

  Désirée van der Heijde, Joachim Sieper, Walter P Maksymowych, Maxime Dougados, Rubén Burgos-Vargas, Robert Landewé, Martin Rudwaleit, Jürgen Braun
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  ABSTRACT: This paper presents the second update of the Assessment in SpondyloArthritis international Society (ASAS) consensus statement on the use of anti-tumour necrosis factor (anti-TNF) agents in patients with axial spondyloarthritis (SpA). A major change from the previous recommendations is that patients fulfilling the ASAS axial SpA criteria, which also include patients fulfilling the modified New York criteria for ankylosing spondylitis, can be treated with anti-TNF agents. This makes an earlier start in the disease process possible. A second major change is the mandatory pretreatment before anti-TNF agents can be started. All patients should have tried a minimum of two non-steroidal anti-inflammatory drugs for a minimum of 4 weeks in total. This is significantly shorter than the previous requirement of 3 months. As previously, patients with axial symptoms require no further pretreatment. Patients with symptomatic peripheral symptoms should normally have had an adequate therapeutic trial of a disease-modifying antirheumatic drug, preferably sulfasalazine. Sulfasalazine is no longer mandatory in this group of patients. Finally, efficacy should be evaluated after at least 12 weeks. The remaining recommendations stayed largely unchanged.
  Annals of the rheumatic diseases 06/2011; 70(6):905-8. · 8.11 Impact Factor
• Article: Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis.

  Denis Poddubnyy, Martin Rudwaleit, Hildrun Haibel, Joachim Listing, Elisabeth Märker-Hermann, Henning Zeidler, Jürgen Braun, Joachim Sieper
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  ABSTRACT: To assess the progression of radiographic sacroiliitis in a cohort of patients with early axial spondyloarthritis over a period of 2 years and to explore predictors of progression. 210 patients with axial spondyloarthritis from the German Spondyloarthritis Inception Cohort have been selected for this analysis based on availability of radiographs at baseline and after 2 years of follow-up. Radiographs were centrally digitised and the sacroiliac joints were scored independently according to the grading system of the modified New York criteria for ankylosing spondylitis (AS) by two trained readers. The readers scored both time points simultaneously but were blinded for the time point and for all clinical data. 115 patients (54.8%) fulfilled the modified New York criteria for AS in their radiographic part in the opinion of both readers at baseline, while 95 patients (45.2%) were classified as non-radiographic axial spondyloarthritis. More patients with non-radiographic spondyloarthritis (10.5%) compared with AS (4.4%) showed an estimated 'true' progression by at least one grade according to both readers, although the difference between the two groups was statistically non-significant. The rate of progression from non-radiographic axial spondyloarthritis to AS was 11.6% over 2 years. An elevated level of C-reactive protein (CRP) at baseline was a strong positive predictor of radiographic sacroiliitis progression in non-radiographic axial spondyloarthritis and AS (OR 3.65 and 5.08, respectively, p<0.05). Progression of radiographic sacroiliitis by at least one grade after 2 years occurs only in a small percentage of patients with early axial spondyloarthritis. An elevated level of CRP was found to be a strong positive predictor of sacroiliitis progression.
  Annals of the rheumatic diseases 05/2011; 70(8):1369-74. · 8.11 Impact Factor
• Chapter: T Cell Responses in Reactive and Lyme Arthritis

  Joachim Sieper, Jürgen Braun
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  ABSTRACT: In reactive arthritis (ReA) and Lyme arthritis the triggering antigen is known, which is in contrast to that for rheumatoid arthritis. Thus, in these two arthritides the antigen-specific T cell response can be investigated in detail and lessons learned for other rheumatic diseases: not only for rheumatoid arthritis but also for ankylosing spondylitis where T cells are also believed to play an important role in the pathogenesis.
  03/2011: pages 169-187;