[Spondyloarthritides--new aspects of classification, diagnosis and therapy].
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Antirheumatic Agents↗
Biomedical subjects
H Zeidler
Publications and source records attributed to H Zeidler.
[Systemic inflammatory rheumatic diseases competence network].
The foundation of the competence network for rheumatology, which is funded by the "Bundesministerium für Bildung und Forschung" (BMBF) since 1999, succeeded to create a unique research structure in Germany: medical doctors and scientists from six university rheumatology centres (Berlin, Düsseldorf, Erlangen, Freiburg, Hannover und Lübeck/Bad Bramstedt) work closely together with scientists doing basic research at the Deutsches Rheuma-Forschungszentrum (DRFZ), with rheumatological hospitals, reha-clinics, and rheumatologists. Jointly they are searching for causes of systemic inflammatory rheumatic diseases and try to improve therapies-nationwide and with an interdisciplinary approach. The primary objective of this collaboration is to transfer new scientific insights more rapidly in order to improve methods for diagnosis and patients treatment.
Biomedical Research↗
[Fibromyalgia].
Fibromyalgia is a frequent disorder of the middle aged, particularly in women characterized by diffuse and widespread pain, and tenderness on palpation at characteristic sites, called tender points. Additional characteristic symptoms of fibromyalgia are fatigue, sleep disturbances, irritable bowel and bladder syndrome, chronic headaches, paresthesia, hearing and vestibular dysfunction. The etiology remains poorly understood. Diagnosis is based on characteristic symptoms, presence of tender points and exclusion of similar confounding conditions. Because of the unknown etiology, all therapies are symptomatic. Interdisciplinary combined treatments can relief the pain in about 50% of the patients.
Combined Modality Therapy↗
[Contribution of leflunomide to the cost effectiveness of sequential DMARD therapy of rheumatoid arthritis in Germany].
Since November 1999, leflunomide (LEF), an innovative disease-modifying antirheumatic drug (DMARD), is available in Germany for treatment of rheumatoid arthritis (RA). LEF slows radiographic disease progression and improves functional capacity as well as healthrelated quality of life of RA patients. Resources for health care of the patients are limited in Germany as in all other countries. The purpose of the analysis therefore was to compare the cost effectiveness of the following alternatives: LEF in sequential monotherapy with other DMARDs versus sequential monotherapy of other DMARDs. The target variables of this cost-effectiveness comparison were additional direct costs per ACR20-response year (ACR20RY) gained and per quality-adjusted life year (QALY) gained, respectively, each after three years of treatment. The cost-effectiveness comparison was carried out using a modeling study after secondary analysis of relevant data. Oral methotrexate (MTX), sulphasalazine (SSZ), antimalarials (CQ/HCQ), intramuscular gold (IMG), and azathioprine (AZA) were selected as "other" DMARDs representing the current status of sequential monotherapy. Based on health care regulation in Germany-Guidelines on the Prescription of Drugs amended by the Federal Commission of Medical Practitioners and Health Insurance Funds on 10 December 1999-LEF was exclusively considered second within a DMARD sequence. Direct costs were given by outpatient and inpatient treatment, long-term care, and rehabilitation treatment. Prices relate to the period of 1998 to 2001 and were converted to Euro (euro), according to the official exchange rate of 1 euro = 1.95583 DM (1 euro approximately 0.90 US dollars; 2001 values). The comparative cost-effectiveness analysis covered a treatment period of more than one year. To estimate the net present value of future costs and effectiveness, a discount rate of 5% per year was applied. In the case of DMARD-naïve patients with RA, the sequence MTX, LEF, SSZ, IMG, AZA, CQ/HCQ was the most cost effective with direct costs of 7297 euro per ACR20RY and 6499 euro per QALY. In order to estimate the consequences of introducing LEF into the prescribing practice in Germany, the distribution of RA patients by individual DMARD in rheumatological care in 1998 was considered. This distribution was taken from the National Database of the German Collaborative Arthritis Centres. Though the sequences comprising LEF incurred 3% higher direct costs, they led to a higher effectiveness of 6% and 3% in the case of ACR20RYs and QALYs, respectively. Choosing sequences comprising LEF, there were additional direct costs of 5004 euro per ACR20RY gained and 8301 euro per QALY gained, as compared to the corresponding sequences without LEF. In comprehensive sensitivity analyses, the robustness of the model and its results was shown. The contribution of LEF to the cost effectiveness of sequential DMARD therapy is obvious. The modeling study revealed advantages for the patients and the cost carriers. Though there were initially higher medication costs of the sequences comprising LEF, these costs were nearly compensated to remaining excess costs of just 3% after three years. This was caused by cost savings in other sectors of the health care system due to the higher effectiveness of the sequences comprising LEF.
Anti-Inflammatory Agents, Non-Steroidal↗
[Rheumatology: Integration into student training--the RISA- Study. Results of a survey exploring the scale of education and training in rheumatology at German universities].
During the Bone and Joint Decade 2000-2010, national and international rheumatological societies campaign for improvements of undergraduate training in the field of musculoskeletal diseases. In 2002, the Committee for Undergraduate Training of the German Society for Rheumatology (DGRh) performed a survey in order to estimate the extent of rheumatological undergraduate training at German universities. A questionnaire was sent to all university hospitals for internal medicine and for orthopaedics. The items of the survey covered the qualification of the teachers, the number and the time frame of lessons and courses, as well as the items of the curriculum in rheumatology. With 95% of the universities responding, a broad variation of the quality of rheumatological training became obvious, ranging from the absence of competent teaching to a comprehensive curriculum covering theory and practical training. Only a minority of universities fulfilled the recommendations of the DGRh for undergraduate education. The most substantial deficits are found in practical training, caused by insufficiently small numbers of patients seen by the medical students, and by the short duration of the practical courses. The insights described here should lead to the adaptation of the level of education in the field of rheumatology to the demands of a society with growing musculoskeletal problems.
Clinical Competence↗
[Pathogenesis of ankylosing spondylitis-mechanisms of disease manifestation and chronicity].
Despite intensive research during the last three decades, it is still not clear which precise mechanisms determine the interactions between host factors (HLA-B27 and other genes, cytokines, T lymphocytes) and microbial factors leading to the manifestation and chronicity of ankylosing spondylitis (AS). Rheumatologists and histopathologists have focused their interest on decoding the immune-mediated inflammatory processes and on studying new bone formation and ankylosis. Concerning the genetic basis of AS, there is considerable effort in large genome-wide and candidate gene analyses to discover new genes that are associated with AS. Moreover, such genetic studies could identify genomic regions that determine clinical manifestations and the course of disease.
Autoimmune Diseases↗
[Diagnosis of reactive arthritis].
For the diagnosis of reactive arthritis, there is no single test. A combination of different parameters such as clinical presentation and laboratory parameters is necessary. Here we suggest a procedure for clinical practice of which tests should be performed when, based on the individual situation. To assess the clinical value of a test, it is not only necessary to know the specificity and sensitivity of a test but also the assumed likelihood of the disease (pretest probability).
Algorithms↗
[Conceptual and methodological basics of cost assessments in rheumatology].
Cost-of-illness studies in rheumatic conditions show an enormous variability in reported costs. Reasons are-among others-a lack of standardization with regards to relevant cost domains and the utilization of various insufficiently validated costing sources. A flow scheme is presented which may serve as a systematic basis for a valid costing analysis. The scheme includes: i) Selection of relevant cost domains. A comprehensive matrix of cost domains may be used as a framework. According to the specific aims of any costing study individual domains might be selected. ii) An adequate level of detail has to be determined taking into account factors such as the validity of the data collection and the feasibility. iii) Appropriate objective (i. e. usage of administrative data) or subjective (i. e. patient-derived) data sources have to be identified under consideration of respective strengths and weaknesses. While administrative sources provide a valid access to costing data accessibility and feasibility are important advantages of patient-derived costing procedures. iv) During data collection the potential bias due to protocol-driven costs and the differentiation of disease-related from other health care costs should be considered. v) The data analysis should support a transparent presentation of the costing data both in physical and monetary units. In summary, no 'gold standard' has been established for costing studies yet. However, valid costing approaches might follow the flow scheme presented in this analysis.
Arthritis, Rheumatoid↗
Re: Layton et al. Comparison of the incidence rates of selected gastrointestinal events reported for patients prescribed rofecoxib and meloxicam in general practice in England using prescription-event monitoring data.
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Adverse Drug Reaction Reporting Systems↗
Technical validation of cDNA based microarray as screening technique to identify candidate genes in synovial tissue biopsy specimens from patients with spondyloarthropathy.
OBJECTIVES: To validate the use of cDNA based microarray on synovial biopsies by analysing the experimental variability due to amplification of RNA, reproducibility of the assay, heterogeneity of the tissue, and statistical analysis. METHODS: Total RNA was extracted from three spondyloarthropathy (SpA) and three osteoarthritis (OA) synovial tissue biopsy specimens and from the peripheral blood mononuclear cells (PBMC) of four healthy donors. Exponential RNA amplification by SMART-PCR was compared with linear amplification. Reproducibility was tested by comparing different microarray systems and by performing duplicate experiments. Sample heterogeneity was assessed by comparing overall gene expression profiles, histopathology, and analysis of genes expressed in the synovium and normal PBMC. Statistical analysis using t test and Bonferroni adjustment was verified by permutation of class labels. RESULTS: Gene expression was concordant in 12/14 (86%) cytokine/chemokine genes between both microarrays and different RNA amplification systems. When one microarray system was used, expressed genes were 78-95% concordant in duplicate experiments. Gene expression profiles had a higher degree of similarity between SpA synovium than between PBMC or OA synovium despite clear histopathological differences between synovial samples. Comparison of SpA synovium with OA synovium and with PBMC yielded 11 and 18 expressed transcripts, respectively; six were shared in both comparisons. Permutations of SpA and OA samples yielded only one expressed gene in 19 comparisons. CONCLUSIONS: These data provide evidence that microarrays can be used for analysis of synovial tissue biopsies with high reproducibility and low variability of the generated gene expression profiles.
Adult↗
Musculoskeletal pain in Europe: its impact and a comparison of population and medical perceptions of treatment in eight European countries.
OBJECTIVES: To describe the impact of musculoskeletal pain (MP); to compare management of MP by the population and by primary care physicians; and to identify misconceptions about treatment. METHODS: 5803 people with MP and 1483 primary care physicians, randomly selected, in eight European countries were interviewed by telephone. A structured questionnaire was used to ask about usual management of MP and perceived benefits and risks of treatment. Current health status (SF-12) was also assessed. RESULTS: From primary care physicians' perceptions, MP appears to be well managed. All presenting patients are offered some form of treatment, 90% or more doctors are trying to improve patients' quality of life, and most are aware and concerned about the risks of treatment with NSAIDs. From a population perspective, up to 27% of people with pain do not seek medical help and of those who do, several wait months/years before seeing a doctor. 55% or fewer patients who have seen a doctor are currently receiving prescription treatment for their pain. Communication between doctors and patients is poor; few patients are given information about their condition; and many have misconceptions about treatment. CONCLUSIONS: Management of MP is similar across eight European countries, but there is discordance between physician and patient perspectives of care. Some people with pain have never sought medical help despite being in constant/daily pain. Those who do seek help receive little written information or explanation and many have misperceptions about the benefits and risks of treatment that limit their ability to actively participate in decisions about their care.
Anti-Inflammatory Agents, Non-Steroidal↗
Alpha beta but not gamma delta T cell clones in synovial fluids of patients with reactive arthritis show active transcription of tumour necrosis factor alpha and interferon gamma.
OBJECTIVE: To compare the cytokine expression profile of three CD8+, three CD4+, and three gammadelta+ T cell clones all derived from the synovial fluids of three patients with reactive arthritis (ReA). METHODS: Complementary DNA based microarrays containing the specific sequence of 56 cytokine transcripts were used for screening. Selected genes were confirmed by reverse transcriptase-polymerase chain reaction assay. RESULTS: Microarray showed that transcripts encoding for interferon gamma and tumour necrosis factor alpha were expressed by all CD8+ and CD4+ T cell clones. However, gammadelta+ T cells predominantly expressed transforming growth factor beta2 and granulocyte monocyte-colony stimulating factor. CONCLUSION: T lymphocyte clones from the joint of patients with ReA exhibit differential cytokine expression profiles. CD8+ and CD4+ T cells demonstrate a Th1 mediated profile, whereas gammadelta+ T cells show a more heterogeneous and less proinflammatory Th3 driven pattern.
Adult↗
[When the cardiac patient with arthritis needs aspirin and NSAID: how to protect the stomach?].
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Anti-Inflammatory Agents, Non-Steroidal↗
Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial.
OBJECTIVE: Treatment of ankylosing spondylitis (AS) with infliximab, an anti-tumor necrosis factor alpha monoclonal antibody, was shown to be efficacious in patients with active disease during a 3-month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1-year period. METHODS: This study was an open, observational, extension study of a 3-month, randomized, placebo-controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12-week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent-to-treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31-63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36-67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in approximately 70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study. CONCLUSION: Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications.
Acute-Phase Proteins↗
Implementing standardized cost categories within economic evaluations in musculoskeletal diseases.
We present a matrix of relevant resource utilization domains for use in standardizing applied cost assessment in musculoskeletal conditions. In addition,we highlight the importance of selecting cost categories during the development of an economic evaluation. A set of four steps was applied: (a) literature search identifying economic evaluations in osteoarthritis and osteoporosis, (b) listing and aggregation of cost categories mentioned in the identified articles, (c) development of a matrix of resource utilization domains, and (d) qualitative discussion regarding the generalizability of the matrix to other musculoskeletal conditions such as rheumatoid arthritis. We examined 41 full-length articles (25 cost-of-illness studies or cost-comparisons, 14 cost-effectiveness analyses, and 2 cost-utility analyses), of which 16 studies focused on osteoarthritis and 25 on osteoporosis. The reviewed studies used a total of 151 different cost categories which, after adjustment for synonymous labeling, made up 34 cost categories. A matrix of 16 separate resource utilization domains was developed including seven outpatient, three inpatient, four other disease-related, and two productivity cost domains. We found that cost assessment in economic evaluation in the key musculo-skeletal diseases (osteoarthritis, osteoporosis, and rheumatoid arthritis) is performed rather inhomogeneously. A generalized matrix of applicable resource utilization domains and a flowchart facilitating the development of appropriate resource utilization data have been developed.
Journal Article↗
Efficacy and safety of the fully human anti-tumour necrosis factor alpha monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study.
OBJECTIVES: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA). METHODS: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs. RESULTS: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p</=0.01). Additionally, ACR responses with adalimumab were achieved more rapidly than with placebo, with 82/115 (71%) of the ultimate ACR20 response rate to adalimumab treatment achieved at week 2. At week 12, for adalimumab 20, 40, and 80 mg, ACR20 response rates were 50.7%, 57.1%, and 54.2%, respectively, versus 10.0% for placebo (p</=0.001 for all comparisons); ACR50 rates were 23.9%, 27.1%, and 19.4%, respectively, versus 1.4% for placebo (p</=0.001 for all comparisons); and ACR70 rates were 11.3%, 10.0%, and 8.3%, respectively, versus 0.0% for placebo (p</=0.05 for all comparisons). All adalimumab doses significantly improved all ACR core criteria at all assessments. The 40 mg and 80 mg doses provided similar benefit. Adalimumab at all doses was generally well tolerated, with only mild or moderate adverse events. Completion rates were 87% for adalimumab and 67% for placebo. CONCLUSIONS: Adalimumab given as monotreatment to patients with longstanding, severe RA refractory to traditional DMARDs produced a rapid, sustained response and was safe and well tolerated, with no dose limiting side effects.
Adalimumab↗
Costs of rheumatoid arthritis in Germany: a micro-costing approach based on healthcare payer's data sources.
OBJECTIVE: To develop a systematic set of German cost data in rheumatoid arthritis (RA) based solely on valid healthcare payer's cost data sources. METHODS: Retrospectively one year cost data of 338 patients with RA were generated and analysed. The cost data were derived from a major statutory health insurance plan ("Allgemeine Ortskrankenkasse Niedersachsen") and the regional physicians' association ("Kassenärztliche Vereinigung Niedersachsen"). The recently published matrix of cost domains in RA was applied to structure the analysis. Descriptive statistics were used to analyse the data. RESULTS: The total direct costs for the 338 patients during one year (third quarter 2000 to second quarter 2001) were euro 3815 per patient-year. RA related direct costs were euro 2312 per patient-year. Outpatient costs accounted for 73.7%, inpatient costs for 24.0%, and other disease related costs for 2.3% of RA related direct costs. Outpatients cost drivers were RA related drugs (euro 1019 per patient-year), physician visits (euro 323 per patient-year), diagnostic and therapeutic procedures and tests (euro 185 per patient-year), and devices and aids (euro;168 per patient-year). 98 patients were retired prematurely owing to RA related work disability and incurred costs of euro;8358 per retired patient-year. 96 patients were gainfully employed and incurred sick leave costs of euro 2835 per employed patient-year. CONCLUSION: Micro-costing based on healthcare payer's data provides a relatively conservative albeit highly accurate estimate of costs in RA. Both RA related and non-RA related costs must be taken into account. In gainfully employed patients and in patients who receive RA related retirement payments productivity costs exceed direct costs.
Adult↗
Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial.
UNLABELLED: BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis factor (TNF)-alpha, in treatment of such patients. METHODS: In this 12-week placebo-controlled multicentre study, we randomly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn from the study. Our primary outcome was regression of disease activity of at least 50%. To assess response, we used validated clinical criteria from the ankylosing spondylitis assessment working group, including disease activity (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life (short form 36). Analyses were done by intention to treat. FINDINGS: 18 (53%) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23-61], p<0.0001). Function and quality of life also improved significantly on infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment with infliximab was generally well tolerated, but three patients had to stop treatment because of systemic tuberculosis, allergic granulomatosis of the lung, or mild leucopenia. INTERPRETATION: Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis. Since there are some potentially serious adverse effects, we recommend that this treatment mainly be used in co-operation with rheumatological centres.
Adult↗