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J Sieper

Publications and source records attributed to J Sieper.

At least 19 recordsLinked to original sources
PubMed2007

[Revision of the recommendations of the Commission on Pharmacotherapy of the German society for Rheumatology. Therapy with tumour necrosis factor blockers for inflammatory rheumatic illnesses].

Inflammatory rheumatic illnesses are associated with various types of pain as well as handicaps. The so called basic therapies are not sufficiently effective in many patients or are terminated due to side effects. This is where tumor necrosis factor blockers (TNF) can be used. In many cases, they lead to a substantial improvement of the symptoms, a reduction in disease related laboratory parameters, improvement in quality of life to stopping disease related damage when their effect is rapid. Common and severe side effects are few, although long-term data are still limited. The following contribution lists recommendations for the indications and symptomatology for the use of TNF blockers.

Antirheumatic Agents↗
PubMed2006

Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis.

OBJECTIVE: To compare the efficacy, pharmacokinetics and safety of etanercept 50 mg once weekly with 25 mg twice weekly and placebo in patients with ankylosing spondylitis. METHODS: A 12-week, double-blind, placebo-controlled study compared the effects of etanercept 50 mg once weekly, etanercept 25 mg twice weekly and placebo in 356 patients with active ankylosing spondylitis (3:3:1 randomisation, respectively). The primary end point was the proportion of patients achieving a response at week 12 based on the Assessment in Ankylosing Spondylitis Working Group criteria (ASAS 20). The pharmacokinetics of etanercept 50 mg once weekly and 25 mg twice weekly were analysed. RESULTS: Baseline characteristics and disease activity were similar among the three groups: etanercept 50 mg once weekly, etanercept 25 mg twice weekly and placebo. The percentage of patients discontinuing therapy was 9.0%, 9.3% and 13.7% for the three respective groups. ASAS 20 response at 12 weeks was achieved by 74.2% of patients with etanercept 50 mg once weekly and 71.3% of those with etanercept 25 mg twice weekly, both significantly higher than the percentage of patients taking placebo (37.3%, p<0.001). Percentages of patients with ASAS 5/6 response (70.3%, 72.0% and 27.5%, respectively; p<0.001) and those with ASAS 40 response (58.1%, 53.3% and 21.6%, respectively; p<0.001) followed a similar pattern. Significant improvement (p<0.05) was seen in measures of disease activity, back pain, morning stiffness and C reactive protein levels as early as 2 weeks. Serum etanercept exposure was similar between the etanercept groups. Incidence of treatment-emergent adverse events, including infections, was similar among all three groups, and no unexpected safety issues were identified. CONCLUSIONS: Patients with ankylosing spondylitis can expect a comparable significant improvement in clinical outcomes with similar safety when treated with etanercept 50 mg once weekly or with 25 mg twice weekly.

Adult↗
PubMed2006

No efficacy of subcutaneous methotrexate in active ankylosing spondylitis: a 16-week open-label trial.

OBJECTIVE: To examine the potential therapeutic effect of methotrexate 20 mg given weekly as subcutaneous injections to 20 patients with ankylosing spondylitis refractory to non-steroidal antirheumatic drugs. PATIENTS AND METHODS: 20 patients with ankylosing spondylitis, a mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 5.6 (range 4-9.3) and predominantly axial manifestations were treated with weekly 15 mg methotrexate subcutaneously for 4 weeks, which was then increased to 20 mg subcutaneously for the next 12 weeks. Clinical outcome assessments included, among others, BASDAI score physical function, spinal mobility, patients' and physicians' global assessment (visual analogue scale), peripheral joint assessment, quality of life (Short Form 36) and C reactive protein. The primary end point of the study was a 20% improvement on the ASsessments in Ankylosing Spondylitis (ASAS 20) scale. RESULTS: Using an intention-to-treat analysis, ASAS 20 was achieved in only 25% of patients. An ASAS 40 response was achieved in 10% of patients, and no patient reached an ASAS 70 response or the ASAS criteria for partial remission. For the mean BASDAI score, no change was observed between baseline and week 16 (baseline 5.6 v week 16, 5.6). No improvement was observed in any of the clinical parameters or C reactive protein, except a small but non-significant decrease in the number of swollen joints. CONCLUSIONS: In this open study, methotrexate did not show any benefit for axial manifestations in patients with active ankylosing spondylitis beyond the expected placebo response.

Adult↗
PubMed2006

Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial.

OBJECTIVES: To assess the effect of sulfasalazine (SSZ) on inflammatory back pain (IBP) due to active undifferentiated spondyloarthritis (uSpA) or ankylosing spondylitis in patients with symptom duration <5 years. METHODS: Patients with IBP and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >3 from 12 centres were randomly assigned to 24 weeks' treatment with SSZ 2 g/day or placebo. The primary outcome variable was the change in BASDAI over 6 months. Secondary outcomes included measures of spinal pain, physical function and inflammation. RESULTS: 230 patients (50% men, age range 18-64 years, 67% human leucocyte antigen B27 positive) were treated with either SSZ 2x1 g/day or placebo for 6 months. Enthesitis was found in 50%, and peripheral arthritis in 47% of the patients. The mean (SD) BASDAI dropped markedly in both groups: by 3.7 (2.7) and 3.8 (2.4), respectively, as did most secondary outcome measures. No noticeable difference in treatment was observed between groups. Patients with IBP and no peripheral arthritis had significantly (p = 0.03) more benefit with SSZ (BASDAI 5.1 (1.3) to 2.8 (2.3)) than with placebo (5.2 (1.6) to 3.8 (2.4)). Spinal pain (p = 0.03) and morning stiffness (p = 0.05) improved with SSZ in these patients, but other secondary outcomes were not markedly different. CONCLUSION: SSZ was no better than placebo for the treatment of the signs and symptoms of uSpA; however, SSZ was more effective than placebo in the subgroup of patients with IBP and no peripheral arthritis.

Adolescent↗
PubMed2006

An international study on starting tumour necrosis factor-blocking agents in ankylosing spondylitis.

OBJECTIVES: To determine the type and proportion of patients with ankylosing spondylitis who rheumatologists consider to be candidates for treatment with tumour necrosis factor (TNF)-blocking agents, and to what extent this is in agreement with the ASsessment in Ankylosing Spondylitis (ASAS) international working group recommendations on initiation of treatment with anti-TNF agents. METHODS: Participants were rheumatologists from 10 different countries, who were considered to be experts in treating patients with ankylosing spondylitis and in the use of anti-TNF treatment, but were unaware of the ASAS recommendations (unpublished at the time of study in 2003). The first 10 consecutive patients with ankylosing spondylitis seen by the rheumatologist were evaluated as to whether the patient was a candidate for anti-TNF treatment. Thereafter, a metrologist assessed the patient for disease activity and severity, and collected data on demographics and treatment. RESULTS: Complete data were available for 1207 of the 1284 patients and were used for analysis. Overall, the rheumatologists indicated that they would initiate TNF-blocking agents in 49.3% of patients, ranging from 37.2% patients in Canada to 78.3% in Australia. These candidates had higher disease activity, higher levels of acute-phase reactants, worse spinal mobility, worse function, more often hip involvement and a higher prevalence of sick leave. Of all patients considered to be candidates, 40% did not fulfil ASAS recommendations with respect to previous use of non-steroidal anti-inflammatory drugs (NSAIDs; at least two NSAIDs) or Bath Ankylosing Spondylitis Disease Activity Index (>or=4). Conversely, 36% of patients who did not fulfil the NSAID or BASDAI recommendations were still considered to be candidates for TNF-blocking treatment. OBJECTIVE: variables, such as C reactive protein, erythrocyte sedimentation rate or magnetic resonance activity, were considered less important than disease activity in the decision on starting TNF-blocking drugs. The only important objective criterion was rapid radiographic progression. CONCLUSION: Rheumatologists wanted to initiate TNF-blocking drugs in roughly half of the patients with ankylosing spondylitis. However, there was a wide variation across countries and doctors. Rheumatologists considered both disease activity and severity to be determinants of starting TNF blockers, but their decision was often in disagreement with ASAS recommendations.

Adult↗
PubMed2006

Definition of disease duration in ankylosing spondylitis: reassessing the concept.

The concept and definition of disease duration in patients with ankylosing spondylitis is ambiguous, and often many years pass between the onset of symptoms and diagnosis. Members of the Assessment in Ankylosing Spondylitis (ASAS) International Working Group by consensus recently recommended identifying specific components of the medical history to better define and document the concept of disease duration. These include (1) the time of onset of the first symptoms of axial manifestations (including inflammatory back pain); (2) the time of onset of the first symptoms of each individual manifestation, which may be an extra-axial sign or symptom of ankylosing spondylitis, such as peripheral arthritis and enthesitis; (3) the time of onset of associated diseases belonging to the spondyloarthritides, in particular acute anterior uveitis, inflammatory bowel disease and psoriasis; and (4) the time since actual diagnosis by a healthcare provider. Such uniformity in data collection will ensure comparability across studies and facilitate future research.

Acute Disease↗
PubMed2006

Can unresolved infection precipitate autoimmune disease?

Autoimmune diseases are frequently postulated to arise as post-infectious phenomena. Here we survey the evidence supporting these theories, with particular emphasis on Crohn's disease and ankylosing spondylitis. Direct proof that infection establishes persistent autoimmunity remains lacking, although it may provoke a prolonged inflammatory response when occurring on a susceptible immunological background. The argument of infective causality is by no means trivial, since it carries important consequences for the safety of vaccine development.

Animals↗
PubMed2006

[Outcome parameters in ankylosing spondylitis].

Ankylosing spondylitis (AS) is a frequent inflammatory rheumatic disease and prototype of the Spondyloarthitides (SpA). During the last years outcome parameters have been developed to evaluate different aspects of the disease. Among these are the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI), numeric rating scales for general pain, night pain, patients and physicians global assessment, as well as questionnaires to evaluate quality of life as the short Form (SF)- 36, Euroquol 5 Dimensions (EQ-5D), or the AS specific the ASQuol. These outcome parameters are the basis to conduct clinical trials. The ASessements in AS (ASAS) improvement criteria were developed to evaluate the short term efficacy of Non-Steroidal Antirheumatic Drugs (NSAIDs) and adjusted for the measurement of the high efficacy of the TNF-alpha blocking agents. To examine the x-rays of sacroiliac joints (SIG), the radiological criteria as part of the modified New York criteria are mostly used. For the x-rays of the spine the Bath AS Radiology Index (BASRI) is valuable in daily practice, but the modified Stokes AS Spine Score (mSASSS) is more sensitive for clinical trials. To examine Magnetic Resonance Images (MRI) of SIG and spine also scores are currently developed. Altogether, using the new outcome parameters it was possible to demonstrate the strikingly high efficacy of theTNF-alpha blocking agents. However, it could also be shown that conventional disease modifying antirheumatic drugs (DMARDs) are not effective in the treatment of the axial forms of SpA.

Disease Progression↗
PubMed2006

[Spondylarthritides].

Ankylosing spondylitis (AS) is the major subtype and a major outcome of an interrelated group of rheumatic diseases now named as spondyloarthritides (SpA). The most important clinical features of this group are inflammatory back pain (IBP), asymmetric peripheral oligoarthritis, predominantly of the lower limbs, and enthesitis. Established classification criteria for AS and SpA are known to perform less well in early disease stages. This partly contributes to the delay in diagnosis, mainly due the high frequency of back pain in the population. The methods for making an early diagnosis have recently improved. The major factors involved in this improvement are HLA B27 and magnetic resonance imaging of the sacroiliac joints, but also of the spine. Conventional radiography, however, is still the gold standard. International recommendations for the management of AS have recently been published. Conventional medical treatment is based mainly on the use of non-steroidal anti-inflammatory agents (NSAIDs); patients with peripheral arthritis may be treated with sulfasalazine. Patients with persistently active disease benefit from therapy with anti-TNF agents. Physiotherapy is of major importance in the general approach to patients with SpA, especially with AS.

Adalimumab↗
PubMed2006

[Recommendations for the management of ankylosing spodylitis after ASAS/EULAR. Evaluation in the German language area].

AIM: Our aim was to adapt and implement the evidence based recommendations for the management of ankylosing spodylitis (AS) of the "Assessments in AS" (ASAS) International Working Group together with the European League Against Rheumatism (EULAR) within the framework of a competence network (CN) in rheumatology in the German language area. METHODS: The ASAS/EULAR project calculated the effective size (ES), rate ratio, number of patients requiring treatment (number needed to treat, NNT) and the incremental cost-effectiveness ratio (ICER). The strength of the recommendations was determined through the evidence level found in the literature, the risk-benefit trade-off and the clinical experience of the experts. The recommendations were recently published in English. All of the centers taking part in the study area Spondyloarthritis (SpA) CN, as well as an additional 35 experts, were sent the English manuscript. All 35 participants were asked to evaluate the ten main management recommendations on a scale from 0 to 10. RESULTS: The recommendations encompass the use of drugs such as non-steroid anti-inflammatories (NSAR), which, along with conventional NSAR include coxibs and the parallel application of gastroprotectives, so called disease-modifying anti-rheumatic drugs, biologicals, simple analgesics, local and systematic glucocorticoids, non-drug therapies (such as patient training, medical training therapy and physiotherapy), in addition to surgical treatment methods. Moreover, three general recommendations were formulated and a therapy scheme created, taking into consideration the various clinical manifestations. The strength of the ASAS/EULAR recommendations was generally high. There was a marked consensus between the German speaking experts and the international proposal: a mean of 9.13 with relatively low variation between the recommendations. SUMMARY: Ten key recommendations for the treatment of AS were developed. These were strengthened by a systematic search of the literature and by expert consensus. The large group of German speaking experts were largely in agreement with the proposal. This can be seen as a starting point for the dissemination and implementation of the recommendations.

Analgesics↗
PubMed2006

[Ankylosing spondylitis--current state of imaging including scoring methods].

Conventional radiography and magnetic resonance imaging (MRI) are currently the most widely used imaging methods for the initial diagnostic evaluation and follow-up of patients with ankylosing spondylitis (AS). Scintigraphy, computed tomography (CT), and positron emission tomography (PET) only play minor roles, although some are being further developed. AS is characterized by inflammatory changes to the sacroiliac joints (SIJs) and spine, as well as asymmetrical arthritis of the peripheral joints and joints near the trunk. The diagnosis of AS is based on clinical parameters and the presence of chronic inflammatory changes to the SIJs on conventional radiographs. Typical radiographic changes also involve the spine. MRI depicts not only chronic changes, but also active inflammatory lesions, which are important for the diagnosis of early disease and precursors of AS. The scoring system of choice for quantifying spinal changes depicted by conventional radiography is the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). MRI allows the quantitative evaluation of changes involving the SIJs and the spine. Various MRI scoring systems have been proposed to quantify these changes, but they require further validation. This review article presents the imaging modalities used in AS patients, typical findings, and relevant methods of analysis. The most recent developments are discussed.

Diagnostic Imaging↗
PubMed2005

Outcome of patients with active ankylosing spondylitis after two years of therapy with etanercept: clinical and magnetic resonance imaging data.

OBJECTIVE: To examine the long-term outcome of patients with active ankylosing spondylitis (AS) clinically and by magnetic resonance imaging (MRI) after continuous treatment with the tumor necrosis factor (TNF) receptor fusion protein etanercept over 2 years. METHODS: Overall, 26 patients with active AS were treated with etanercept 25 mg twice daily subcutaneously, twice weekly with no concomitant disease-modifying antirheumatic drugs (DMARDs) or steroids. The clinical response was assessed by standardized parameters. Inflammatory spinal lesions were quantified by the ASspiMRI-a rating gadolinium-enhanced (T1-weighted gadolinium diethylenetriaminepentaacetic acid) and STIR MRI sequences. The primary outcome was a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) improvement > or =50% after 2 years of etanercept therapy compared with the baseline value of the study. RESULTS: Overall, 21 (70%) of 30 patients completed year 2. In the intent-to-treat analysis, 54% of the patients showed a 50% improvement according to the BASDAI and a 40% improvement according to the Assessment in Ankylosing Spondylitis (ASAS) criteria. In the completer analysis, 9 (43%) of 21 patients were in partial remission according to ASAS criteria. Mean +/- SD BASDAI scores, which were elevated at baseline (6.3 +/- 1.6), remained low: 2.7 +/- 2.4 after 2 years compared with 2.6 +/- 2.2 at week 54. In accordance, all other clinical parameters showed sustained improvement during year 2. The majority of patients had no disease activity flares. MRI evaluation showed a 75% improvement of active spinal lesions, but minor spinal inflammation was still present in 64% of the patients after 2 years. There were 2 serious adverse events leading to discontinuation of etanercept. CONCLUSION: The clinical efficacy and safety of etanercept in patients with active AS without simultaneous administration of DMARDs or steroids over 2 years of continuous treatment is confirmed. Spinal inflammation as depicted by MRI decreased significantly, but a few patients still had some spinal inflammation even after long-term anti-TNF therapy.

Adult↗
PubMed2005

Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases.

OBJECTIVE: To characterise the immunohistological features of sacroiliitis in ankylosing spondylitis (AS) at different disease stages. METHODS: Biopsy samples from sacroiliac joints (SIJs) of five patients with AS, two with early, three with advanced changes and samples from age matched controls from one necropsy SIJ and two iliac bone marrow (BM) biopsies were studied. Paraffin sections were immunostained in triplicate for T cells (CD3, CD8), macrophages (CD68), and the cytokines tumour necrosis factor alpha (TNFalpha), interferon gamma, interleukin (IL) 1beta, IL6, IL10, and transforming growth factor beta1 (TGFbeta1). Stained cells were counted over one entire high power field (x400) per section in BM, cartilage, and other connective tissue (CT). Results are the mean of three sections. RESULTS: CD3+ T cells were numerous in the BM of early AS, and in the CT of one patient with early and one with late AS, with variable proportions of CD8+ T cells. All patients with AS had more CD68+ macrophages than controls in BM and CT; in cartilage, one patient with early and one with late AS had increased CD68+ cells, some being osteoclasts. The patient with very early AS had large numbers of TNFalpha cells in the three tissular areas; for the other patient with early disease they were found only in CT and cartilage. IL6 was seen in 4/4 patients with AS in most areas. Patients with early disease had more T cells, TNFalpha, and IL6, and patients with advanced AS more TGFbeta1. CONCLUSION: The immunohistological findings of a limited sample suggest a role for BM in sacroiliitis, for TNFalpha and IL6 in early, active lesions, and for TGFbeta1 at the time of secondary cartilage and bone proliferation.

Adolescent↗
PubMed2005

ASAS/EULAR recommendations for the management of ankylosing spondylitis.

OBJECTIVE: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. METHODS: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. RESULTS: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis.

OBJECTIVE: To update the international recommendations for use of anti-tumour necrosis factor (TNF) agents in the treatment of ankylosing spondylitis. METHODS: The published recommendations on anti-TNF treatment in ankylosing spondylitis formed the basis of the update. A questionnaire was sent to the ASAS (assessment in ankylosing spondylitis) members before the final decisions were agreed upon at an international meeting of the ASAS working group. RESULTS: Only minor changes to the original consensus statement were required. For the initiation of anti-TNF treatment, there should be: a diagnosis of definitive ankylosing spondylitis (normally based on modified New York criteria); active disease for at least four weeks, as defined by a sustained Bath ankylosing spondylitis disease activity index (BASDAI) of > or =4 on a 0-10 scale and expert opinion based on clinical findings; refractory disease, defined by failure of at least two non-steroidal anti-inflammatory drugs during a three month period, failure of intra-articular steroids (if indicated), and failure of sulfasalazine in patients with predominantly peripheral arthritis; and application of the usual precautions and contraindications for biological treatment. For monitoring anti-TNF treatment: both the ASAS core set for clinical practice and the BASDAI should be followed after the initiation of treatment. Discontinuation of anti-TNF treatment in non-responders should be considered after 6-12 weeks. Response is defined by improvement of at least 50% or 2 units (on a 0-10 scale) of the BASDAI. CONCLUSIONS: This updated consensus statement is recommended in guiding clinical practice and as a basis for developing national guidelines. Evaluation and regular update of this consensus statement is subject to further research by the ASAS group.

Antirheumatic Agents↗