Rheumatoid Arthritis: Zeidler H

Merkesdal S, Zeidler H. · Division of Rheumatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30623 Hannover, Germany. · Curr Rheumatol Rep. · Pubmed #16045826 No free full text.

This publication has no abstract.

Merkesdal S, Ruof J, Mittendorf T, Zeidler H. · Hannover Medical School, Division of Rheumatology, Carl-Neuberg-Str. 1, 30623 Hannover, Germany. · Expert Opin Pharmacother. · Pubmed #15330726 No free full text.

Abstract: The current literature covering cost-effectiveness and cost-utility analyses of biological treatments in patients with rheumatoid arthritis (RA) are reviewed in order to discuss options and limitations for future application of these highly priced drugs in routine clinical practice. The cost-effectiveness and cost-utility ratios of the studies analysed are converted into the corresponding Euros of the publication year. Etanercept treatment achieved a cost-effectiveness ratio of 44,300 Euros (2002)/ACR 20 (20% response according to American College of Rheumatology criteria) and 43,100 Euros (2002)/ACR 70WR (ACR 70 weighted response) compared with sulfasalazine and methotrexate, respectively, in methotrexate-naive RA. In methotrexate-resistant RA, the combination of etanercept and methotrexate is compared to a combination therapy of methotrexate, sulfasalazine and hydroxychloroquine revealing costs of 46,100 Euros (2000)/ACR 20, and 37,700 Euros/ACR 70WR. The cost-utility ratios for infliximab treatment range from 16,000 Euros to almost 166,000/QALY (quality adjusted life-year) gained, the studies investigating etanercept treatment show a ratio of approximately 25,000 Euros and 120,000/QALY gained. No substantial differences of cost-utilities of infliximab and etanercept were found. The administration of these drugs as third-line therapy is regarded cost-effective compared to other well-accepted therapies with comparable cost-utility ratios of < 50,000 Euros/QALY gained. Still, data on economic outcomes of RA trials are sparse and further cost-effectiveness and cost-utility evaluations are needed.

Zeidler H, Merkesdal S, Hülsemann JL. · Division of Rheumatology, Department of Internal Medicine, Medical School Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. · Clin Exp Rheumatol. · Pubmed #14969060 No free full text.

Abstract: Early arthritis is challenging because the clinical picture often does not allow a distinction between rheumatoid arthritis (RA), self-limiting disease, and other forms of inflammatory arthritis. In Germany the first early synovitis clinic and several inception cohorts of patients with early RA were initiated and evaluated during the 1980s and 1990s to learn more about diagnostic classification, psycho-social problems and socio-economical status including sick-leave, work loss, and indirect costs of patients with early arthritis and early RA. Unclassified arthritis was described as the most frequent diagnosis and the term "undifferentiated arthritis" was chosen to underline the heterogeneity of theses arthritides and the preliminary state of this classification as a working diagnosis. A large National Databank of the German Regional Collaborative Arthritis Centres has been established over the last 10 years. In total, there are some 170,000 cases in the database. Moreover, a prospective multicentre inception cohort of early RA of less than 1 year's disease duration has been started recently to evaluate parameters of potential relevance for the pathogenesis of RA and eventually for the prediction of erosive disease. Studies are in progress to test the diagnostic performance of specific antibodies and antibody patterns for RA. Another topic of research addresses the identification of bacterial DNA in synovial fluid and synovial tissues to improve the differentiation of patients with reactive arthritis from those with early RA and to narrow the working diagnosis of undifferentiated arthritis.

Schnarr S, Kuipers JG, Zeidler H. · Hannover Medical School, Department of Internal Medicine, University of Hannover, Germany. · Clin Exp Rheumatol. · Pubmed #12463462 No free full text.

Abstract: The cytokine tumour necrosis factor (TNF)-alpha plays a major role in the spinal inflammatory process of spondyloarthropathy. In contrast to rheumatoid arthritis, disease modifying antirheumatic drugs have not been proved effective against inflammation and progressive ankylosis. Initial studies on TNFalpha inhibitors in ankylosing spondylitis are promising and raise the question as to whether early stages of the disease, mostly classified as "undifferentiated spondyloarthropathy" (uSpA), should also be treated with TNFalpha inhibitors. This article summarises the preliminary results of 11 uSpA patients in 4 different trials treated with TNFalpha inhibitors.

Merkesdal S, Ruof J, Mittendorf T, Mau W, Zeidler H. · Abteilung für Rheumatologie Medizinische Hochschule Hannover Carl-Neuberg Str. 1 30625 Hannover, Germany. · Z Rheumatol. · Pubmed #11974488 No free full text.

Abstract: Costs of illness are of major economic relevance in rheumatoid arthritis (RA) as in other chronic diseases. Overall costs of 15,000 Euro/year: 10,000 Euro indirect costs, and 5000 Euro direct costs are estimated, respectively. A further detailed analysis of direct costs underlines that inpatient care (50%) is the most prominent cost driver. Medication costs are also evaluated in detail since they are expected to gain importance with the introduction of the more expensive biologicals. While annual costs for regular disease modifying drugs (DMARDs) vary from 160 to 5000 Euro per patient, costs for the new biologicals amount up to 20,000 Euro (100-125% of the current estimated overall costs). For a comparison of different therapeutic strategies, costs are related to effectiveness in cost-effectiveness analyses. Based on present clinical trials, the ratios of medication costs and response according to the ACR 20-criteria of various DMARDs and biologicals are compared. The most cost-effective medication is sulfasalzine, followed by methotrexate, and leflunomide. Combining etanercept and methotrexate is preferable to methotrexate monotherapy and the combination of infliximab and methotrexate. This review shows that important economic issues in RA have already been addressed by applying cost-of-illness analyses and cost-effectiveness analyses. However, the knowledge about cost-effective therapeutic options is still scarce. Thus, primary data will have to be obtained using standardized approaches. These economic findings can be taken into account in the development of disease-management recommendations for RA-therapy.

Ruof J, Merkesdal S, Huelsemann JL, Schoeffski O, Maetzel A, Mau W, Zeidler H. · Division of Rheumatology, Hannover Medical School, Forschungsstelle Gesundheitsökonomie, Universität Hannover, Germany. · J Rheumatol. · Pubmed #11296978 No free full text.

Abstract: We compared the major characteristics of internationally applied cost assessment instruments (CAI) in rheumatic conditions. Fifteen utilization questionnaires were identified and assessed using a structured approach. The forms differed considerably with respect to applied characteristics: length (3-113 items), recall period (between 1 week and 1 year), format (2 interview, 13 self-administered), response categories, cost units (physical vs monetary), and cost domains covered. While all included a gross assessment of outpatient and inpatient costs, the level of disaggregation differed. Only a few CAI included an assessment of other direct disease related costs (e.g., home remodeling or home health care services) and out-of-pocket expenditure. Productivity costs were included in all but 2 CAI. Efforts to further standardize the applied CAI should (1) be based on sound psychometric data, (2) define a required core set of cost domains covered, (3) discriminate between generic and relevant disease related cost components, and (4) examine the feasibility of developing international standards for cost data.

Merkesdal S, Ruof J, Huelsemann JL, Schoeffski O, Maetzel A, Mau W, Zeidler H. · Division of Rheumatology, Hannover Medical School, Center for Health Economics, University of Hannover, Germany. · J Rheumatol. · Pubmed #11296977 No free full text.

Abstract: The aim of our study was to comprehensively review and critically appraise the cost domains used in economic evaluations of the rheumatic diseases and to use this information to propose standardization of cost domains. The literature search identified 210 abstracts, 32 of which included original cost data. The listed cost categories were grouped into 3 major areas: (direct) health care costs, other (direct) disease related costs, and productivity costs (indirect costs). The number of individual cost categories was reduced by considering the following criteria: (1) inclusion of all relevant cost domains; (2) avoidance of double counting; (3) summarizing of related categories under one representative heading; (4) feasibility of level of aggregation. After adjustment for synonymous labeling, 38 cost categories remained. The subsequent development of a classification scheme of cost categories led to a set of 19 separate cost domains including 7 outpatient, 3 inpatient, 6 other disease related, and 3 productivity cost domains. This literature review indicates that cost assessment in economic evaluations in rheumatoid arthritis lacks standardization. A preliminary scheme to categorize cost assessment in rheumatic conditions is presented. The adoption of standards for economic evaluation would greatly facilitate national and international comparisons.

Radbruch A, Peter HH, Zeidler H. · Deutsches Rheumaforschungszentrum Berlin. · Internist (Berl). · Pubmed #11244873 No free full text.

This publication has no abstract.

Mau W, Zeidler H. · Abteilung Rheumatologie, Medizinischen Hochschule Hannover. · Versicherungsmedizin. · Pubmed #10516834 No free full text.

Abstract: The spectrum of rheumatoid arthritis (RA) ranges from benign remitting manifestations to rapidly progressive forms with increased mortality. About 10% of the patients show an intractable rapidly progressive course associated with severe extraarticular manifestations. Within the first three years, 70% of the patients develop radiological erosions of the joints and 31% deformities of the hands. Life expectancy is shortened by 3-18 years. Particularly, infections are more frequent causes of death in RA compared with controls. Work disability occurs in about a quarter of the patients within the first three years of RA and in 43-85% after eight to ten years. The ratio of direct to indirect costs is 1:3 in RA. Preliminary data show that regular rheumatological treatment leads to a marked reduction in indirect costs caused by production loss. The most important early indicators of an unfavourable disease course are the large number of swollen joints, early severe functional impairment, highly elevated laboratory markers of inflammation and rheumatoid factor. Knowledge of the current data regarding the course and prognosis of RA are helpful for assessment of the disease for insurance purposes.

Mau W, Zeidler H. · Abteilung Rheumatologie, Medizinischen Hochschule Hannover. · Versicherungsmedizin. · Pubmed #10420834 No free full text.

Abstract: Rheumatoid arthritis is an inflammatory systemic disease mainly affecting the joints. Frequent extra-articular manifestations are often recognized too late. Particularly the skin, the cardiovascular system, the kidneys, the eyes, the gastrointestinal tract, the liver, the nervous system and the blood may be involved. Examples of important complications affecting different organs are bacterial infections, AA-amyloidosis and hyperviscosity syndrome. Current data on the different disease manifestations and complications provide the basis for the assessment of the morbidity and mortality relevant for insurance purposes.

Merkesdal S, Ruof J, Huelsemann JL, Mittendorf T, Handelmann S, Mau W, Zeidler H. · Division of Rheumatology, Hannover Medical School, Hannover, Germany. · Arthritis Rheum. · Pubmed #15818718 links to  free full text

Abstract: OBJECTIVE: To render information on the accuracy of patient-reported indirect cost data compared with payer-derived data of the real indirect costs on a patient-by-patient basis concerning disease-related productivity losses in rheumatoid arthritis (RA). METHODS: The assessment of indirect cost data was part of a clinical, multicenter, randomized RA trial. A total of 234 patients of working age with a diagnosis of RA (according to 1987 American College of Rheumatology criteria) were recruited. Demographics of the cohort were mean age 53 years, mean disease duration 8 years, 76% were women, and all had membership in the regional statutory health insurance plan. Every 3 months corresponding indirect cost data were derived for the cohort from a health economic questionnaire for cost assessment in patients with RA and the payer's database over a period of 18 months. Comparative statistical analyses were performed between patient-reported and insurance claims data. RESULTS: The mean annual productivity losses due to sick leave amounted to 14 and 17 days per patient (questionnaire versus payer data), and productivity losses due to work disability amounted to 3 days (both); monetary valuation renders overall costs of 1,240 and 1,590, respectively. The difference of 17% in overall productivity losses is not significant. Comparison of productivity losses reveals a strong correlation of r = 0.83 in those due to sick leave and of kappa = 0.84 in those due to work disability between questionnaire and payer data. CONCLUSION: The comparison of questionnaire and payer data shows that RA patients report their productivity losses adequately. Indirect cost assessment should therefore be included in further RA trials and observational studies.

van de Putte LB, Rau R, Breedveld FC, Kalden JR, Malaise MG, van Riel PL, Schattenkirchner M, Emery P, Burmester GR, Zeidler H, Moutsopoulos HM, Beck K, Kupper H. · University Hospital Nijmegen, Nijmegen, The Netherlands. · Ann Rheum Dis. · Pubmed #14644854 links to  free full text

Abstract: 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.

Ruof J, Hülsemann JL, Mittendorf T, Handelmann S, von der Schulenburg JM, Zeidler H, Merkesdal S. · Division of Rheumatology, Hannover Medical School, Hannover, Germany. · Ann Rheum Dis. · Pubmed #12759292 links to  free full text

Abstract: 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.

Rau R, Wassenberg S, Zeidler H, Anonymous00085. · Rheumaklinik Ratingen, Evangelisches Fachkrankenhaus, Rosenstr. 2, 40882 Ratingen, Germany. · Z Rheumatol. · Pubmed #11155812 No free full text.

Abstract: OBJECTIVE: To test if continuous LDPT decreases radiographically detectable joint destruction in early RA. METHODS: Patients with active RA (< 2 years from symptom onset) were treated with prednisolone 5 mg daily or placebo for 2 years in a double blind, randomized, multi-center study. At the same time in all patients DMARD treatment with either gold sodium thiomalate (GSTM) or methotrexate (MTX) was started; in the case of side effects or inefficacy the medication could be switched to the other DMARD. Radiographs of hands and forefeet were taken at baseline and after 6, 12 and 24 months. All radiographs were evaluated by one observer (S.W.) knowing the time sequence of the film but unaware of the patient identity or treatment using the Ratingen score and van der Heijde's modification of Sharp's method. RESULTS: 196 patients were included; 76 patients completed the study per protocol. Of these patients 34 were treated with prednisolone, 42 with placebo, 48 initially with GSTM, 28 with MTX. 17 patients switched from GSTM to MTX, 1 from MTX to GSTM. The mean values of the radiographic scores of both groups are given in the table. During the first year, especially during the first 6 months, the radiographic progression within the prednisolone group was significantly lower than in the placebo group: the Sharp erosion score increased by 0.4% of the maximum possible score during the first and the second 6 months in the prednisolone group, while in the placebo group there was an increase of 1.8% during the first 6 months and 0.8% during the second 6 months. During the second year the progression was significantly lower (-0.1% in the prednisolone group, 0.2% in the placebo group). After 24 months the total score had increased by 2.6% of the maximum score in the placebo group and by 1.1% in the prednisolone group. The results of the completers were confirmed by the intention-to-treat analysis (80 patients in the prednisolone group, 86 patients in the placebo group). CONCLUSION: Continuous low dose prednisolone treatment with 5 mg daily over 2 years administered in addition to conventional DMARD treatment with MTX or GSTM decreases radiographic progression in early RA. The results of the study also show that in the placebo group there is a sharp decrease of the progression after 6-12 months as a result of the DMARD treatment. During the second year there is nearly no progression in this group. The data of the "completers" are confirmed by the analysis of the "intention to treat" population.

Emery P, Zeidler H, Kvien TK, Guslandi M, Naudin R, Stead H, Verburg KM, Isakson PC, Hubbard RC, Geis GS. · Department of Rheumatology and Rehabilitation, University of Leeds, UK. · Lancet. · Pubmed #10609815 No free full text.

Abstract: BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclo-oxygenase (COX), which leads to suppression of COX-1-mediated production of gastrointestinal-protective prostaglandins. Gastrointestinal injury is a common outcome. We compared the efficacy, safety, and tolerability of long-term therapy with celecoxib, a COX-1 sparing inhibitor of COX-2, with diclofenac, a non-specific COX inhibitor. METHODS: 655 patients with adult-onset rheumatoid arthritis of at least 6 months' duration were randomly assigned oral celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily for 24 weeks. Anti-inflammatory and analgesic activity and tolerability were assessed at baseline, every 4 weeks, and at week 24. We assessed gastrointestinal safety by upper-gastrointestinal endoscopy within 7 days of the last treatment dose at centres where the procedure was available. Analysis was by intention-to-treat. FINDINGS: 430 patients underwent endoscopy (celecoxib n=212, diclofenac n=218). The two drugs were similar in management of rheumatoid arthritis pain and inflammation. Gastroduodenal ulcers were detected endoscopically in 33 (15%) patients treated with diclofenac and in eight (4%) in the celecoxib group (p<0.001). The rate of withdrawal for any gastrointestinal-related adverse event, most commonly abdominal pain, diarrhoea, and dyspepsia, was nearly three times higher in the diclofenac-treated group than in the celecoxib group (16 vs 6%; p<0.001). INTERPRETATION: Celecoxib showed sustained anti-inflammatory and analgesic activity similar to diclofenac, with a lower frequency of upper gastrointestinal ulceration or gastrointestinal adverse events, and tolerability was better.

Dougados M, Combe B, Cantagrel A, Goupille P, Olive P, Schattenkirchner M, Meusser S, Paimela L, Rau R, Zeidler H, Leirisalo-Repo M, Peldan K. · Institut de Rhumatologie, Hardy B, Hôpital Cochin, Paris, France. · Ann Rheum Dis. · Pubmed #10364900 links to  free full text

Abstract: OBJECTIVES: To investigate the potential clinical benefit of a combination therapy. METHODS: 205 patients fulfilling the ACR criteria for rheumatoid arthritis (RA), not treated with disease modifying antirheumatoid drugs previously, with an early (< or = 1 year duration), active (Disease Activity Score (DAS) > 3.0), rheumatoid factor and/or HLA DR 1/4 positive disease were randomised between sulphasalazine (SASP) 2000 (maximum 3000) mg daily (n = 68), or methotrexate (MTX) 7.5 (maximum 15) mg weekly (n = 69) or the combination (SASP + MTX) of both (n = 68). RESULTS: The mean changes in the DAS during the one year follow up of the study was -1.15, -0.87, -1.26 in the SASP, MTX, and SASP + MTX group respectively (p = 0.019). However, there was no statistically significant difference in terms of either EULAR good responders 34%, 38%, 38% or ACR criteria responders 59%, 59%, 65% in the SASP, MTX, and SASP + MTX group respectively. Radiological progression evaluated by the modified Sharp score was very modest in the three groups: mean changes in erosion score: +2.4, +2.4, +1.9, in narrowing score: +2.3, +2.1, +1.6 and in total damage score: +4.6, +4.5, +3.5, in the SASP, MTX, and SASP + MTX groups respectively. Adverse events occurred more frequently in the SASP + MTX group 91% versus 75% in the SASP and MTX group (p = 0.025). Nausea was the most frequent side effect: 32%, 23%, 49% in the SASP, MTX, and SASP + MTX groups respectively (p = 0.007). CONCLUSION: This study suggests that an early initiation therapy of disease modifying drug seems to be of benefit. However, this study was unable to demonstrate a clinically relevant superiority of the combination therapy although several outcomes were in favour of this observation. The tolerability of the three treatment modalities seems acceptable.

Barthel C, Yeremenko N, Jacobs R, Schmidt RE, Bernateck M, Zeidler H, Tak PP, Baeten D, Rihl M. · Clinic for Immunology and Rheumatology, Hannover Medical School (MHH), Carl-Neuberg-Strasse 1, Hannover 30625, Germany. · Arthritis Res Ther. · Pubmed #19490633 links to  free full text

Abstract: INTRODUCTION: We previously described the presence of nerve growth factor receptors in the inflamed synovial compartment. Here we investigated the presence of the corresponding nerve growth factors, with special focus on nerve growth factor (NGF). METHODS: mRNA expression levels of four ligands (NGF, brain derived growth factor (BDNF), neurotrophin (NT)-3, NT-4) and their four corresponding receptors (tyrosine kinase (trk) A, trkB, trkC, NGFRp75) were determined in the synovial fluid (SF) cells of 9 patients with rheumatoid arthritis (RA) and 16 with spondyloarthritis (SpA) and compared with 7 osteoarthritis (OA) patients. NGF was also determined in synovial tissue (ST) biopsies of 10 RA and 10 SpA patients. The production of NGF by monocytes and lymphocytes was assessed by flow cytometry of SF cells, synovial tissue derived fibroblast-like synoviocytes (FLS) were assessed by ELISA on culture supernatant. RESULTS: SF cell analysis revealed a clear BDNF and NGF mRNA expression, with significantly higher NGF expression in RA and SpA patients than in the OA group. NGF expression was higher in ST samples of RA as compared to SpA. Using intracellular FACS analysis, we could demonstrate the presence of the NGF protein in the two inflammatory arthritis groups on both CD3+ T lymphocytes and CD14+ cells, i.e. monocytes/macrophages, whereas cultured FLS did not produce NGF in vitro. CONCLUSIONS: Neurotrophins and especially NGF are expressed in the synovial fluid and tissue of patients with peripheral synovitis. The presence of neurotrophins as well as their receptors, in particular the NGF/trkA-p75 axis in peripheral synovitis warrants further functional investigation of their active involvement in chronic inflammatory arthritis.

Westhoff G, Schneider M, Raspe H, Zeidler H, Runge C, Volmer T, Zink A. · Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany. · Rheumatology (Oxford). · Pubmed #19321515 No free full text.

Abstract: OBJECTIVES: To assess the quality of health care for RA patients in the general population of Germany. METHODS: A three-stage population survey was conducted to identify individuals with RA using a health care access panel (18-79 years; n = 70,112). A 20-item postal screening questionnaire of musculoskeletal symptoms and diagnoses was followed by a detailed questionnaire for those who indicated the possibility of having RA. Respondents who fulfilled the modified ACR decision tree, who reported an RA diagnosis, care by a rheumatologist or the use of DMARDs were asked to participate in a clinical examination by rheumatologists who diagnosed the participants and rated the adequacy of treatment. RESULTS: RA could not be ruled out in 1177 cases, of which 643 agreed to participate in the clinical examination, which was finally attended by 317 participants. Attendees did not differ with regard to any health or treatment measure from those who did not attend. Forty-one RA patients were detected. Of them, 93% had seen a rheumatologist at least once and 63% within the last 12 months. A total of 73% had received DMARD therapy at some time and 59% were currently receiving it. An unmet need for DMARDs was discovered in 29% of the RA attendees. It pertained almost exclusively to the seronegative cases of which 29% had a need to start and 17% to increase a DMARD therapy according to the opinion of the examining rheumatologist. CONCLUSION: Health care for RA patients has improved significantly since the last German RA survey in 1989. However, DMARD prescription still does not meet clinical recommendations, specifically in RF-negative patients. Since seronegative RA is a treatable disease, this group should not be overlooked.

Rihl M, Kellner H, Kellner W, Barthel C, Yu DT, Tak PP, Zeidler H, Baeten D. · Hannover Medical School, Hannover, Germany. · Arthritis Rheum. · Pubmed #18975340 No free full text.

Abstract: OBJECTIVE: Understanding of the molecular pathophysiology of spondylarthritis (SpA) remains largely elusive. This is related both to the complexity of the disease (axial versus peripheral disease, inflammation versus tissue remodeling) and to the difficulty in obtaining samples from primary disease sites. This study was undertaken to explore a gene expression approach for identifying novel candidate mediators of SpA. METHODS: Sacroiliac joint fluid aspirates from 3 SpA patients with active sacroiliitis were studied by microarray analysis. The expression of selected candidate molecules in peripheral synovitis was confirmed by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: Microarray analysis identified 4 sacroiliitis gene clusters, containing a total of 47 messenger RNA (mRNA) transcripts. Two clusters contained genes expressed in all sacroiliitis samples, corresponding to both known and unsuspected candidate mediators of SpA pathology. These included proinflammatory molecules as well as molecules involved in tissue remodeling, such as transforming growth factor beta2. Of the novel candidate genes selected for confirmation, interleukin-7 (IL-7) mRNA expression was higher in SpA peripheral synovial fluid and synovial tissue samples than in osteoarthritis samples, and similar to expression in rheumatoid arthritis (RA) samples. At the protein level, synovial fluid IL-7 levels were even higher in SpA than in RA, despite lower levels of tumor necrosis factor alpha and IL-1beta. CONCLUSION: In the present study, both known and unsuspected candidate mediators of SpA pathogenesis were identified, including IL-7. The specific overexpression of IL-7 at sites of peripheral synovitis in SpA suggests that further functional investigations of the role of this cytokine in SpA pathogenesis are warranted.

Kuipers JG, Sibilia J, Bas S, Gaston H, Granfors K, Vischer TL, Hajjaj-Hassouni N, Ladjouze-Rezig A, Sellami S, Wollenhaupt J, Zeidler H, Schumacher HR, Dougados M. · Department of Rheumatology, Rotes Kreuz Krankenhaus, Bremen, Germany. · Clin Rheumatol. · Pubmed #18688674 No free full text.

Abstract: Little is known about the possible role of Chlamydia in patients with reactive or unclassified arthritis in North Africa. This study used polymerase chain reaction (PCR) to survey this population. In addition, we compared the results in three different laboratories for PCR analyses for Chlamydia trachomatis (Ct) in synovial fluid (SF) and tissue (ST) from these North African patients with reactive arthritis (ReA), undifferentiated arthritis (UA), and in rheumatoid arthritis (RA) and osteoarthritis (OA). Eight ReA (six posturethritic, two postenteritic), 23 UA, 13 OA, and 12 RA patients were studied in Algeria, Morocco, and Tunisia. Serum, SF, and ST were obtained from each patient. Ct-PCR was performed in the three different laboratories and compared to Ct-serology [microimmunofluorescence (MIF) and anti-hsp60 enzyme-linked immunosorbent assay (ELISA)] performed in one laboratory. The rate of Ct-PCR positivity in SF/ST was low: none out of the eight ReA and three out of 23 UA patients. In the controls, Ct DNA was detected in two OA SF and in one RA SF. There was no concordance for Ct-PCR positivity between the three laboratories. MIF suggested previous Ct infection (IgG-positive) in two out of five posturethritic ReA, none out of one postenteritic ReA, one out of 17 UA, and nine out of 21 RA/OA patients tested. No MIF-positive patient was PCR-positive from SF or ST. However, anti-hsp60 IgG was detected in all four out of four patients positive by PCR and in 11 out of 44 PCR-negative patients (p = 0.002). In this multinational comparative study, the rate of Ct-PCR-positive synovial specimens in North African ReA/UA patients was low. Concordance among the three PCR testing laboratories was poor indicating the need for test standardization. All Ct-PCR-positive patients were found positive by anti-hsp60 IgG serology.

Hülsemann JL, Mattussek S, Zeh S, Zeidler H. · Abteilung Rheumatologie, Medizinische Hochschule, Carl-Neuberg-Strasse 1, 30625 Hannover. · Z Rheumatol. · Pubmed #17294063 No free full text.

Abstract: AIM: Between 2000 and 2003 the collaborative arthritis center Hanover implemented a quality management program for patients with rheumatoid arthritis (RA). Fourteen rheumatologists in private practice participated in this model project. One of the aims of the project was to improve the cooperation between primary care physicians and rheumatologists. A survey of the primary care physicians was conducted to evaluate rheumatological care. METHODS: A total of 340 patients with RA were included in the study. All primary care physicians of these patients were informed about the goals of the project and asked to answer a questionnaire on cooperation with rheumatologists. The questionnaire contained 14 questions and was sent to 270 primary care physicians. RESULTS: Of the primary care physicians, 83% returned the questionnaire, and 81% percent of these were family practitioners. The primary care physicians treated a mean of 19 patients with RA, of whom 14 were attended in cooperation with rheumatologists. High mean values were found for satisfaction with different aspects of rheumatological patient care on a numerical rating scale from 0 (not satisfied at all) to 10 (completely satisfied). Mean values for satisfaction: diagnosis 7.9, therapy recommendations 7.6, follow-up 7.2,and usefulness of medical report 7.7. A total of 70% of primary care physicians reported difficulties in realizing the recommendations of the rheumatologists. Of the respondents, 90% saw a need for improvement in cooperation with rheumatologists, the most frequently mentioned being the difficulty of consultation with appointments. CONCLUSION: This survey of primary care physicians of patients with RA reveals a positive assessment of the cooperation with rheumatologists. The problems which exist mainly concern the realization of recommendations. There is a great requirement for further improvement in the cooperation between primary care physicians and rheumatologists.

Zeidler H, Kaltwasser JP, Leonard JP, Kohlmann T, Sigmund R, Degner F, Hettich M. · Department of Rheumatology, University of Hannover, Germany. · J Clin Rheumatol. · Pubmed #17041399 No free full text.

Abstract: The goal of this study was to obtain data for prescription habits, tolerability for patients at high risk, and clinical effectiveness of meloxicam administered at 7.5 mg and 15 mg for various rheumatic diseases under real world prescribing conditions. This was a 3-month large-scale prospective observational cohort study in 4000 medical practices throughout Germany shortly after the introduction of meloxicam. To be eligible, patients had to have a diagnosis of acute or chronic active rheumatic disease for which nonsteroidal antiinflammatory drug (NSAID) therapy was required according to the prescribing information. In this study, 13,307 patients receiving meloxicam prescriptions (7.5 mg in 65% and 15 mg in 33%) were observed. The diagnoses of these patients included osteoarthritis (61%), rheumatoid arthritis (24%), ankylosing spondylitis (1.6%), and other rheumatic conditions (28%). A substantial proportion of high risk patients were enrolled: 12% with a previous history of a perforation, ulceration, and bleeding (PUB), 24% with at least one concomitant cardiovascular disorder, and 26% receiving concomitant antihypertensive medication. Many of the patients (58%) had received NSAIDs before meloxicam, including patients with insufficient prior treatment effectiveness (43%) and those with NSAID-related adverse drug reactions (21%). In 85% and 94% of the patients, respectively, effectiveness and tolerability were rated as good or very good. Quality of life and daily functions improved in 64% to 84% of the patients. Only 0.8% of the patients reported gastrointestinal (GI) adverse drug reactions. Four uncomplicated cases of gastric ulceration, one serious perforated gastric ulcer, and one serious ileus complication were reported after incorrect use or overdosing of meloxicam. Treatment with the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam in doses of 7.5 mg and 15 mg resulted in meaningful treatment responses under real life conditions, despite inclusion of a substantial number of patients with insufficient effectiveness of previous use of non-COX-2 selective NSAIDs. All major GI toxicity (PUB) observed was owing to the fact that prescribing conditions were not respected appropriately. Despite a selection of high risk patients overall, GI, cardiovascular, and renal tolerability was favorable.

Huscher D, Merkesdal S, Thiele K, Zeidler H, Schneider M, Zink A, Anonymous00022. · German Rheumatism Research Centre, Berlin, Germany. · Ann Rheum Dis. · Pubmed #16540552 No free full text.

Abstract: OBJECTIVE: To estimate and compare the direct and indirect costs of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE), and to evaluate the effect of sex, disease duration and functional status on the various cost domains. METHODS: Data of outpatients, aged 18-65, with rheumatoid arthritis (n = 4351), ankylosing spondylitis (n = 827), PsA (n = 908) or SLE (n = 844), who were enrolled in the national database of the German collaborative arthritis centres in 2002, were analysed. Data on healthcare consumption, out-of-pocket expenses and productivity losses were derived from doctors and patients. For the calculation of indirect costs, the human capital approach (HCA) and the friction cost approach (FCA) were applied. RESULTS: Mean direct costs amounted to 4737 euros a year in rheumatoid arthritis, 3676 euros in ankylosing spondylitis, 3156 euros in PsA and 3191 euros in SLE. By using the HCA, total costs were calculated at 15,637 euros in rheumatoid arthritis, 13,513 euros in ankylosing spondylitis, 11,075 euros in PsA and 14,411 euros in SLE, whereas with the FCA the numbers were 7899 euros, 7204 euros, 5570 euros and 6518 euros, respectively. Costs increased with disease duration and were strongly dependent on functional status. In patients with the highest disability (<50% of full function), the total costs on applying the HCA were 34,915 euros in rheumatoid arthritis, 29,647 euros in alkylosing spondylitis, 37,440 euros in PsA and 32,296 euros in SLE. CONCLUSION: The costs of illness are high in all four diseases, with a strong effect of functional status on total costs. Indirect costs differ by the factor 3, based on whether the HCA or the FCA is used.

Merkesdal S, Huelsemann JL, Mittendorf T, Zeh S, Zeidler H, Ruof J. · Abt. Rheumatologie, Medizinische Hochschule, Carl-Neuberg-Strasse 1, 30625 Hannover. · Z Rheumatol. · Pubmed #16534538 No free full text.

Abstract: OBJECTIVE: Identification of predictors for the productivity cost components: (1) sick leave, and (2) work disability in gainfully employed and (3) impaired household productivity in unemployed patients with rheumatoid arthritis (RA) from the societal perspective.METHODS: Investigation of productivity costs was linked to a multicenter, randomized, controlled trial evaluating the effectiveness of clinical quality management in 338 patients with RA. The productivity losses were assessed according to the German Guidelines on Health Economic Evaluation. By means of multivariate logistic regression analyses, predictors of sick leave, work disability (employed patients, n=96), and for days confined to bed in unemployed patient (n=242) were determined.RESULTS: Mean annual costs of 970 EUR arose per person taking into consideration all patients (453 EUR sick leave, 63 EUR work disability, 454 EUR impaired productivity of unemployed patients). Disease activity, disease severity, and impaired physical function were global predictors for all of the cost components investigated. Sick leave costs were predicted by prior sick leave periods and the vocational status blue collar worker, work disability costs by sociodemographic variables (marital status, schooling), and the productivity costs of unemployed patients by impaired mental health and impaired physical functions.CONCLUSIONS: Interventions such as reduction in disease progression and control of disease activity, early vocational rehabilitation measures and vocational retraining in patients at risk of quitting working life, and self-management programs to learn coping strategies might decrease future RA-related productivity costs.

Hülsemann JL, Ruof J, Zeidler H, Mittendorf T. · Division of Rheumatology, Hannover Medical School, Hannover, Germany. · Rheumatol Int. · Pubmed #16261384 No free full text.

Abstract: The objective of this study is to review the concept of the 'Hannover Costing Study' and to present and discuss the major insights generated during the course of the project. The costing study was performed in conjunction with a randomized controlled prospective trial assessing the effectiveness of a disease management module in rheumatoid arthritis (RA). A full set of clinical and cost data both from patient-reported and payer-derived cost data was developed. In particular the study included (1) the development of a matrix of cost domains which might be used as a common taxonomy in costing studies, (2) the descriptive analysis of payer derived cost data, (3) the analysis of cost data in patients with uncertain diagnosis; (4) the development and validation of a patient-reported costing instrument, and (5) an assessment of productivity costs. The following are the results (1) the developed matrix of cost domains included 16 separate cost domains: 7 outpatient, 3 inpatient, 4 other disease related, and 2 productivity domains; (2) the micro-costing analysis showed total direct costs of <euro> 3,815 per patient-year (standard error of mean, SEM: <euro>267) and RA-related direct costs were <euro>2,312 per patient-year; (3) in patients with uncertain diagnosis of RA and no treatment with 'Disease Modifying Antirheumatic Drugs' (DMARD) costs were significantly lower; (4) the comparison of patient-reported with payer-reported cost data generally supports the use of highly aggregated items to assess health care utilization in RA; (5) productivity costs in patients that are gainfully employed and in patients who receive RA-related retirement payments exceed RA-related direct costs. Furthermore, RA-patients reported their productivity losses adequately. The study added some additional insights to the following questions: What costs should be collected, what level of detail is required for that task, what patients should by analyzed, and what data sources should be used in further studies in RA.