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J Sieper

Publications and source records attributed to J Sieper.

At least 37 records · Page 2Linked to original sources
PubMed2005

Persistent reduction of spinal inflammation as assessed by magnetic resonance imaging in patients with ankylosing spondylitis after 2 yrs of treatment with the anti-tumour necrosis factor agent infliximab.

OBJECTIVES: Patients with ankylosing spondylitis (AS) benefit from anti-TNF therapy both on a clinical basis and as depicted by magnetic resonance imaging (MRI). It is not known whether spinal inflammation remains suppressed over time. Our objective was to assess spinal inflammation by MRI in AS patients after 2 yr of continuous infliximab treatment. METHODS: Twenty patients with active AS were examined by MRI at baseline, after 3 months (end of placebo-controlled-phase) and after 2 yr of continuous infliximab therapy (5 mg/kg/6 weeks). T1 pre- and post-gadolinium (T1/gadolinium-diethylenetriamine-pentaacetic acid) and short tau inversion recovery (STIR) MRI sequences were performed and read by one blinded reader using the ASspiMRI score. RESULTS: Spinal inflammation, detected by MRI in all patients at baseline, decreased after 3 months only in the infliximab group in both MRI sequences. Persistent improvement of spinal inflammation was seen after 2 yr by scoring STIR sequences, with a mean score of 4.6 +/- 5.9 vs 15.2 +/- 13.2 at baseline (P = 0.01). On an individual level, inflammatory spinal lesions decreased from 6.7 +/- 5.0 per patient at baseline to 2.2 +/- 1.8 after 2 yr (P = 0.003). Improvement in spinal inflammation was found in all patients by both MRI sequences. Only a minor degree but some spinal inflammation was still present after 2 yrs. CONCLUSION: Spinal inflammation in MRI was persistently reduced in all patients constantly treated with infliximab, but it was not completely eradicated. Disease activity parameters did not directly correlate with MRI, but both pointed in the same direction. Both types of information may be useful for the definition of response to anti-TNF therapy.

Adult↗
PubMed2005

Markov model into the cost-utility over five years of etanercept and infliximab compared with usual care in patients with active ankylosing spondylitis.

OBJECTIVE: To estimate the incremental cost-utility of etanercept and infliximab compared with usual care in active ankylosing spondylitis. METHODS: A Markov model over five years with cycle times of three months was computed. Patients included all had active disease, defined as Bath ankylosing spondylitis disease activity index (BASDAI) >or=4 and could reach low disease activity, defined as BASDAI <4. Non-response to tumour necrosis factor alpha (TNFalpha) inhibitors was always followed by cessation of treatment. Response to TNFalpha inhibitors could be followed at any time by either relapse to BASDAI >or=4, leading to cessation of treatment, or toxicity, leading to cessation of treatment if major. Probabilities for efficacy, relapse, and toxicity were derived from two European randomised controlled trials. Utilities and costs assigned to the BASDAI disease states were derived from a two year observational Dutch cohort. In sensitivity analyses probabilities of effectiveness, toxicity, costs, and utilities were varied. RESULTS: Over five years the total quality adjusted life years varied from 2.57 to 2.89 for usual care, compared with 3.13 to 3.42 and 3.07 to 3.35 for etanercept or infliximab. Cumulative costs were between 49,555 to 69,982 for usual care compared with 59,574 to 91,183 or 28,3330 to 106,775 for etanercept and infliximab. This resulted in incremental cost-utility ratios varying between 42,914 and 123,761 per QALY for etanercept compared with usual care and 67,207 to 237,010 for infliximab. The model was sensitive to drug prices. CONCLUSION: Etanercept and infliximab have large clinical effects in ankylosing spondylitis. The present model suggests the high drug costs restricts efficient use in all patients who have a BASDAI >4. The validity of the model is limited by insufficient insight in the natural course of the disease and long term effectiveness and toxicity of TNFalpha inhibitors.

Acute Disease↗
PubMed2005

Magnetic resonance imaging of the spine and the sacroiliac joints in ankylosing spondylitis and undifferentiated spondyloarthritis during treatment with etanercept.

OBJECTIVE: To assess the changes in inflammatory lesions of the spine and the sacroiliac (SI) joints as detected by magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA) with predominant axial symptoms during treatment with etanercept. METHODS: MRI of the spine and/or the SI joints of patients with active AS or axial uSpA was performed at baseline (TP0, n = 25), after 6 weeks (TP1, n = 20), and after 24 weeks of continuous treatment with etanercept (TP2, n = 12). T1 weighted spin echo pre -(T1), post-gadolinium (T1/Gd-DTPA) and short tau inversion recovery (STIR) MRI sequences were used to assess chronic and active spinal lesions using the scoring system ASspiMRI. Active and chronic SI lesions were assessed using a simple scoring system. RESULTS: By use of the definite STIR sequence, significant regression of spinal inflammation was already seen already after 6 weeks in the patients treated with etanercept (mean (SD) 11.2 (13.8) at TP0 v 6.8 (7.9) at TP1; p = 0.023) but not in patients treated with placebo. Continuous treatment with etanercept for 24 weeks reduced active spinal changes by 69% (p = 0.012). T1/Gd-DTPA sequences gave similar results. There was only a trend for a decrease of active inflammatory lesions of the SI joints. CONCLUSIONS: Etanercept treatment in patients with active AS and uSpA leads to regression of active inflammatory lesions of the spine as depicted by MRI. The potential role of etanercept on deceleration of chronic spinal changes needs further study.

Acute Disease↗
PubMed2005

Radiographic progression in patients with ankylosing spondylitis after 2 years of treatment with the tumour necrosis factor alpha antibody infliximab.

BACKGROUND: Anti-tumour necrosis factor (TNF) treatment is clinically efficacious in patients with active ankylosing spondylitis (AS) and leads to improvement of spinal inflammation, as assessed by magnetic resonance imaging. It is unclear whether anti-TNF treatment affects chronic spinal changes in AS. OBJECTIVES: To analyse the effect of infliximab on the radiographic course of AS over 2 years. METHODS: Complete sets of lateral radiographs of the cervical spine and lumbar spine were available from 82 patients from two sources: 41 patients (group 1) had been treated with infliximab (5 mg/kg/6 weeks) as part of a recent randomised controlled trial and 41 patients (group 2) were part of the early German AS cohort (GESPIC), without controlled interventions. Radiographs were obtained at baseline and after 2 years and scored by the modified Stokes AS Spinal Score (mSASSS). RESULTS: Patients in the infliximab group were older, had a longer disease duration, and more radiographic damage at baseline. The mean (SD) mSASSS change was 0.4 (2.7) and 0.7 (2.8) for groups 1 and 2, respectively (p = NS). Radiographic damage at baseline was a predictor for more radiographic progression. Patients with baseline damage who were treated with infliximab showed a trend for less radiographic progression. No correlations between clinical parameters and radiographic progression were found. CONCLUSIONS: Patients with AS treated with infliximab had less radiographic progression after 2 years. Patients with prevalent radiographic damage are prone to develop more damage over time. Infliximab may decelerate radiographic progression in such patients. Larger studies are needed to prove that anti-TNF treatment inhibits structural damage.

Adult↗
PubMed2005

Persistent clinical response to the anti-TNF-alpha antibody infliximab in patients with ankylosing spondylitis over 3 years.

OBJECTIVE: Infliximab, a monoclonal antibody against tumour necrosis factor alpha (TNF-alpha), is approved in Europe for the treatment of patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy. This report provides analyses from a 3-yr extension study, as a follow-up to both the 1- and 2-yr open label extensions of the original 3-month randomized controlled trial of infliximab in patients with AS. METHODS: Of the 49 patients with AS who completed the second year of the study, 46 continued treatment with infliximab 5 mg/kg every 6 weeks up to week 156. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index, the Bath AS Metrology Index, patient's and physician's global assessments, quality of life (Short Form-36), C-reactive protein (CRP) and erythrocyte sedimentation rate were assessed throughout the study period. RESULTS: The improvement of signs and symptoms observed in the majority of the patients during the first and second year was sustained throughout the third year of the study. Forty-three patients (62% of the 69 patients enrolled at baseline and 93% of the patients who started the third year) completed week 156. In the intention-to-treat analysis, an ASAS '5 out of 6' and ASAS 40% response was seen by 46% and 50% of the patients, respectively. The scores for other efficacy assessments were similar to the values observed at weeks 54 and 102. Median CRP levels remained low (1.5 mg/l at week 156). There were no relevant side-effects and no discontinuation because of drug-related adverse events during the third year of the study. CONCLUSIONS: Patients with AS receiving infliximab for 3 yr showed a durable clinical response without loss of efficacy. Long-term infliximab treatment was well tolerated by patients in this study.

Adult↗
PubMed2005

Assessment of acute spinal inflammation in patients with ankylosing spondylitis by magnetic resonance imaging: a comparison between contrast enhanced T1 and short tau inversion recovery (STIR) sequences.

OBJECTIVES: To compare the performance of two different MRI sequences-T(1) weighted, fat saturated, spin echo after application of contrast medium, and short tau inversion recovery (STIR) sequences-to detect spinal inflammation in patients with ankylosing spondylitis (AS). METHODS: Both MRI sequences were performed in 38 patients with active AS and compared using the MRI activity scoring system, ASspiMRI-a. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebral body. RESULTS: Intraclass correlation coefficients were excellent-0.91 and 0.86 for the Gd-DTPA and STIR sequences, respectively. The overall correlation of the single MRI scores for both sequences was also good (r = 0.84, p = 0.01). The intrarater variance was 6.71 and 9.41 and the interrater variance was 13.16 and 19.04 for the Gd-DTPA and STIR sequences, respectively. The smallest detectable distance was 4.7 and 5.6 for the Gd-DTPA and STIR sequences, respectively. The concordance rate for both sequences was 83.5% (range 80.5-87.7% in the three spinal segments). Inflammatory spinal lesions were found in 10.1% of the VUs in the STIR sequence but not in the T(1)/Gd-DTPA sequence, while the T(1)/Gd-DTPA sequence showed inflammatory lesions in 6.4% of the VUs that were found normal by STIR. CONCLUSIONS: Both MRI techniques can evaluate active spinal lesions in patients with AS. More spinal lesions are detected by the STIR sequence, but the reliability between readings and readers is better for the Gd-DTPA sequence. The ASspiMRI-a is a reliable instrument for evaluating acute spinal changes in AS.

Acute Disease↗
PubMed2005

Decreased incidence of anterior uveitis in patients with ankylosing spondylitis treated with the anti-tumor necrosis factor agents infliximab and etanercept.

OBJECTIVE: To estimate the incidence of anterior uveitis in patients with ankylosing spondylitis (AS) who underwent anti-tumor necrosis factor (anti-TNF) therapy, using data from recently performed trials. METHODS: Data from 4 placebo-controlled studies with anti-TNF agents in AS (2 with etanercept and 2 with infliximab) and 3 open-label studies were analyzed for the prestudy prevalence and the incidence of reported flares of anterior uveitis. RESULTS: A total of 717 patients who received treatment for anterior uveitis during the course of published clinical studies were identified by a systematic literature search using Medline. Followup information on the course of anterior uveitis was available for 397 patients. Of these, 297 were exposed to etanercept and 90 were exposed to infliximab for a total of 430 and 146.4 years, respectively. Among 190 patients who received placebo, the overall exposure was 70.5 years. The frequency of flares of anterior uveitis in the placebo group was 15.6 per 100 patient-years (95% confidence interval 7.8-27.9), while the patients treated with anti-TNF agents had a mean of only 6.8 anterior uveitis flares per 100 patient-years (P = 0.01). Flares of anterior uveitis occurred less frequently (although not significantly) in patients treated with infliximab than in patients treated with etanercept (3.4 per 100 patient-years and 7.9 per 100 patient-years, respectively). CONCLUSION: Treatment of AS patients with biologic agents directed against TNFalpha is associated with a significant decrease in the number of anterior uveitis flares. This reduction was slightly more marked among patients treated with infliximab, but the difference was not significant.

Antibodies, Monoclonal↗
PubMed2005

[Early diagnosis of spondyloarthritis with special attention to the axial forms].

The axial spondyloarthritis (SpA) is the most important disease out of the whole group of SpA. If a sacroiliits is clearly detectable by x-rays a diagnosis of ankylosing spondylitis can be made. However, there is still a delay of 5-10 years from the first symptoms until a final diagnosis is made. An important reason for this is the fact that radiological changes are often only detectable after several years of disease, despite the presence of inflammation as detected by MRI and the presence of clinical manifestations such as pain and stiffness. An early diagnosis becomes more and more important because effective therapies have become available which are probably even more effective if given early. New strategies how to make an early diagnosis and how primary care physicians can screen for these patients are discussed.

Atlanto-Axial Joint↗
PubMed2005

Six months open label trial of leflunomide in active ankylosing spondylitis.

OBJECTIVE: To examine the potential therapeutic effects of leflunomide in patients with active AS in an open label study. PATIENTS AND METHODS: Twenty patients with AS fulfilling the 1984 modified New York criteria with a Bath AS Disease Activity Index (BASDAI) >3 were given leflunomide for 6 months. Clinical outcome assessments included disease activity (BASDAI), function (BASFI), metrology (BASMI), patient's and physician's global assessment, peripheral joint assessment, quality of life (SF-36), global pain, and CRP. Primary end point was a reduction of disease activity as measured by the BASDAI of >25% at 6 months. RESULTS: A BASDAI 25% improvement was noted in 5/20 (25%) patients and a BASDAI 50% improvement in 4/20 (20%) patients. The absolute BASDAI did not change significantly over the 6 month study (4.9 at baseline v 4.3 at week 24, p>0.05). Similarly, no significant change was found for the BASFI, BASMI, patient's and physician's global assessment, SF-36 mental component, and CRP. For the 10 patients with peripheral arthritis, the mean number of inflamed joints was significantly reduced from 1.7 at baseline to 0.9 at week 12 (p = 0.034) and 0.2 at week 24 (p = 0.039). CONCLUSION: In this open study of patients with active AS only those with peripheral arthritis improved significantly with leflunomide treatment. Axial symptoms did not improve.

Adult↗
PubMed2005

Very early spondyloarthritis: where the inflammation in the sacroiliac joints starts.

Involvement of the sacroiliac joints (SIJ) is a major and characteristic feature of the spondyloarthritides (SpA). In early ankylosing spondylitis and undifferentiated SpA (uSpA) sacroiliitis is the most common early clinical finding and the presumed first manifestation of the disease. Magnetic resonance imaging has proved useful for visualising inflammation in the SIJ in adults and children. Recently, initial localisation of the inflammation in the SIJ has been described in some detail, but it has not been completely defined to date--either in imaging or in histopathological studies. This is mainly owing to the lack of data in very early disease and the lack of follow up studies. Here we present a patient with early disease, which may augment our understanding of this stage of SpA.

Age of Onset↗
PubMed2005

How early should ankylosing spondylitis be treated with tumour necrosis factor blockers?

Recognition and treatment of ankylosing spondylitis (AS) in the early stages of the disease has yet to be established. This paper considers the evidence available and the questions that need to be answered regarding the benefits of early diagnosis and treatment with tumour necrosis factor (TNF) blockers in AS. The authors conclude that AS can and has to be diagnosed earlier than is being done at present, before radiological changes are evident, and the potential of TNF blockers to induce long term remission if given early enough needs to be clarified.

Antirheumatic Agents↗
PubMed2005

Infliximab for the treatment of ankylosing spondylitis.

Ankylosing spondylitis (AS) had previously been considered as a chronic disease with little therapeutic options. Non-steroidal anti-inflammatory drugs (NSAIDs) and regular physiotherapy were the only treatment modalities available for patients with AS. The introduction of biologics into clinical practice has substantially broadened the therapeutic armamentarium in AS patients who are refractory to NSAIDs. Remicade (infliximab; Centocor, Inc., USA), a chimeric monoclonal antibody, targets TNF-alpha, and by inhibition of this proinflammatory cytokine, exerts strong clinical improvement of signs and symptoms of AS. In AS, infliximab 5 mg/kg body weight is usually given as an infusion at weeks 0, 2 and 6, and every 6 - 8 weeks thereafter. An improvement of the disease activity by at least 50% is seen in as many as 50% of AS patients treated with infliximab in addition to NSAIDs. Back pain and also peripheral manifestations, such as enthesitic sites and arthritis, improve, and quality of life significantly increases. In addition, elevated acute phase reactants return to normal or low levels, and active inflammatory lesions of the spine as detected by magnetic resonance imaging substantially regress during treatment with infliximab. Clinical improvement occurs during the first 2 weeks of treatment and the clinical response to infliximab, if given continuously, is sustained and long-lasting as follow-up data of ongoing studies show. The short-term benefit/risk ratio of infliximab is clearly in favour of the drug, and it is estimated that at present up to 30% of patients with active AS are in need of this kind of effective treatment.

Antibodies, Monoclonal↗
PubMed2004

Long-term efficacy and safety of etanercept after readministration in patients with active ankylosing spondylitis.

OBJECTIVES: Treatment of ankylosing spondylitis (AS) with the tumour necrosis factor alpha (TNF-alpha) receptor fusion protein etanercept has shown efficacy in patients with active disease in randomized controlled trials (RCTs) for limited periods. The objective of the study was to assess the long-term efficacy and safety of etanercept over 1 yr, including discontinuation and readministration. METHODS: In this 54-week open observational study, 26 AS patients received 25 mg etanercept subcutaneously twice weekly after several months of discontinuation following a 6-month RCT with the same agent. All patients who developed high disease activity after cessation of etanercept, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) > or = 4 and pain > or = 4 on a numerical rating scale, entered the study. Standard assessment tools, such as the Bath Ankylosing Spondylitis functional index (BASFI), were used. An intention-to-treat (ITT) and a completer analysis were performed. The results were compared with the baseline values of the open study. RESULTS: Out of the initial 30 patients, 26 (87%) were eligible for the open extension study after a mean of about 27 weeks. At week 54, 23/26 patients (88%) were still on treatment with etanercept. The ITT analysis showed that 58% (95% confidence interval 39-74%) of the patients achieved a 50% improvement of BASDAI at week 54. According to the Assessments in Ankylosing Spondylitis working group criteria, 8/26 patients (31%) were in partial remission at week 54. Function, metrology and quality of life improved significantly. Only one patient had a serious adverse event that resulted in discontinuation. CONCLUSIONS: This study shows that treatment with etanercept is efficacious and safe after readministration over 1 yr in patients with active AS not taking DMARDs or steroids.

Adult↗
PubMed2004

Analysis of the CD8+ T cell response to the G1 domain of aggrecan in ankylosing spondylitis.

BACKGROUND: CD4+ T cell responses to the G1 domain of aggrecan in patients with ankylosing spondylitis (AS) were recently reported. Whether such an immune response can be seen in the CD8+ subpopulation has not yet been determined. OBJECTIVE: To determine if HLA-B27 restricted G1-specific CD8+ T cells are present in AS and to analyse immunodominant CD8+ T cell epitopes. METHODS: Peripheral blood mononuclear cells of 45 patients with AS were stimulated with overlapping 18-mer peptides covering the whole G1 protein. Results were compared with those for patients with rheumatoid arthritis (RA) and healthy controls. For epitope analysis, G1-specific interferon gamma positive (IFNgamma+) T cells were isolated by magnetic activated cell sorting. After in vitro expansion, CD8+ T cells were restimulated with 14 subpools of G1 peptides. T cells responding to G1 peptide subpools were quantified by flow cytometry according to IFNgamma secretion. Predicted peptides were subsequently confirmed by stimulation with single peptides. RESULTS: G1-specific CD8+ T cell responses were found in 29/45 (64%) patients with AS, 18/35 (51%) patients with RA, but not in healthy controls. Five CD8+ T cell epitopes were identified as immunodominant in five patients. However, the T cell response was not HLA-B27 restricted. Nonamer peptides with an HLA-B27 binding motif did not induce a T cell response. CONCLUSION: A G1 peptide-specific CD8+ T cell response is present in AS but also in patients with RA. It does not seem to be HLA-B27 restricted. Whether such a response has a role in the pathogenesis of AS needs clarification.

Adult↗
PubMed2004

Early referral recommendations for ankylosing spondylitis (including pre-radiographic and radiographic forms) in primary care.

An earlier diagnosis of ankylosing spondylitis (AS) is required because there is still a 5-7 year delay between first symptoms and diagnosis, and new effective treatments are available for active disease. Primary care physicians need easy to apply parameters to help them identify patients with suspected AS for onward referral. The best measures found were inflammatory back pain and HLA-B27 positivity.

Adult↗
PubMed2004

Inflammation in ankylosing spondylitis: a systematic description of the extent and frequency of acute spinal changes using magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly used to detect inflammation in the spine of patients with ankylosing spondylitis (AS). OBJECTIVES: To detect differentially the presence and extent of inflammation in the three spinal segments of patients with AS by MRI. METHODS: In 38 patients with active AS, acute spinal lesions were assessed by T(1) weighted, gadolinium enhanced, spin echo MRI (T(1)/Gd-DTPA) and short tau inversion recovery (STIR) sequences. MRI was quantified by the validated scoring system ASspiMRI-a. Acute spinal lesions were detected in the whole spine and in each spinal segment. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebral body. RESULTS: A greater number of inflammatory spinal lesions were found by the STIR sequence than by Gd-DTPA: inflammation was present in 30.6% of the VUs as assessed by STIR, compared with 26.8% of the same VUs assessed by T(1)/Gd-DTPA. Inflammation was found more commonly in the thoracic spine (TS) than in the cervical (CS) or the lumbar spine (LS) with both techniques. When STIR was used, spinal inflammation in the CS, the TS, and LS was detected in 10/38 (26%), 28/38 (74%), and 9/38 (24%) patients, respectively. The VU T7/8 was found to be the VU most often affected by both techniques (27.8% by T(1)/Gd-DTPA and 34.5% by STIR). CONCLUSIONS: Spinal inflammation is a common manifestation in patients with AS, and appears more frequently in the TS. The scoring system ASspiMRI-a can be used for evaluation of acute spinal changes in AS.

Acute Disease↗
PubMed2004

Two year maintenance of efficacy and safety of infliximab in the treatment of ankylosing spondylitis.

OBJECTIVE: To obtain results of the second year extension of an original 3 month randomised, placebo controlled trial (and the 1 year extension study) assessing the use of infliximab, a monoclonal antibody to tumour necrosis factor alpha, for the treatment of patients with ankylosing spondylitis (AS). METHODS: Of the 54 patients with AS who completed the first year of the study, 52 continued to receive infliximab 5 mg/kg every 6 weeks up to week 102. The primary end point was the proportion of patients achieving at least 50% improvement from baseline in the Bath AS Disease Activity Index (BASDAI) at week 102. Other assessments included patient and physician global assessments, quality of life as assessed by Short Form-36, Bath AS Functional Index, Bath AS Metrology Index, and C reactive protein (CRP). RESULTS: Improvement in signs and symptoms of AS seen during the first year of the study was sustained during the second year. Forty nine patients (71% of 69 enrolled patients and 49/52 (94%) patients who started year 2) completed the study up to week 102. Thirty (58%) patients achieved at least 50% improvement from baseline in the BASDAI score at week 102. Scores for other efficacy assessments were similar at weeks 54 and 102. Median CRP levels remained low at weeks 54 and 102 (3.9 and 4.3 mg/l, respectively). Side effects during the second year of the study were similar to those of the first year of treatment with infliximab. CONCLUSIONS: Patients with AS treated for 2 years with infliximab 5 mg/kg exhibited a good and durable clinical response.

Adult↗