Rheumatoid Arthritis: Zink A

Minden K, Niewerth M, Zink A, Ganser G. · HELIOS-Kliniken, Klinikum Berlin-Buch, II. Klinik für Kinderheilkunde und Jugendmedizin und Deutsches Rheumaforschungszentrum Berlin, Forschungsbereich Epidemiologie, Schumannstr. 21/22, 10117 Berlin, Germany. · Z Rheumatol. · Pubmed #15965817 No free full text.

Abstract: Chronic inflammatory rheumatic diseases with onset in childhood often persist into adulthood and result in a considerable number of patients in impairments of body functions and structures, activities at the individual level and participation in society. Continuation of health care beyond adolescence is, therefore, necessary. Its provision should be of high quality, coordinated, uninterrupted, patient-centred and developmentally appropriate to ensure smooth transitions between children's and adult services and positive outcomes of transition for the young people themselves. Existing research is very persuasive on the need to improve transitions for young people with rheumatic diseases. To achieve effective transition, not only disease specific, but also aspects of growth and development have to be taken into account. Paediatric and adult rheumatologists should establish close cooperation and implement specific transition programs to meet the special health care needs of these patients.

Thiele K, Buttgereit F, Huscher D, Zink A, Anonymous00011. · Deutsches Rheuma-Forschungszentrum Berlin, Forschungsbereich Epidemiologie, 10117 Berlin, Germany. · Z Rheumatol. · Pubmed #15868331 No free full text.

Abstract: Systemic GCs are among the most important therapeutic options in modern rheumatology. Due to their fast clinical effects and their high anti-inflammatory potential, they are indispensable in a large number of cases. This applies despite the well-known spectrum of adverse events and despite limited evidence from randomized clinical trials. In this situation, the results of observational studies gain additional importance. They provide information on therapeutic decisions of rheumatologists concerning GC therapy and their combination with other drugs as well as concerning the prevention of adverse events such as GC induced osteoporosis. The data gathered in the national database of the German Collaborative Arthritis Centers show that at the time of documentation 60% of all RA patients were under therapy with GCs, 85% of these were treated with a dosage of up to 7.5 mg/d. GCs are especially frequently used in combination with new or highly potent DMARDs. This underlines that rheumatologists take activity and severity into account in deciding both about GCs and DMARDs. However, there is high practice variation regarding the frequency of GC use among the rheumatological facilities which demonstrates the lack of good evidence.Rheumatologists are aware of various patient risks when prescribing GCs and adapt their therapies to these risks. Two thirds of all patients under GCs were receiving therapy for the prevention or treatment of osteoporosis at documentation, high risk groups such as women over 50 even more frequently. The data emphasize the high importance of GCs in modern rheumatology.

Schädlich PK, Zeidler H, Zink A, Gromnica-Ihle E, Schneider M, Straub C, Brecht JG, Huppertz E. · InForMed GmbH - Outcomes Research and Health Economics, Bureau Itzehoe, Conrad-Roentgen-Strasse 58C, D-25524 Itzehoe, Ingolstadt, Germany. · Pharmacoeconomics. · Pubmed #15853438 No free full text.

Abstract: OBJECTIVE: To estimate the 3-year incremental cost effectiveness and cost utility of introducing leflunomide into sequential therapy, consisting of the most frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted from the societal perspective in Germany using an existing 3-year simulation model, which was adapted to the German healthcare system after secondary analysis of relevant publications and data. DMARD sequences including leflunomide were compared with those excluding leflunomide. Costs comprised direct costs incurred by treatment and indirect costs incurred by loss of productivity (sick leave and premature retirement) of rheumatoid arthritis patients. Effectiveness parameters were given by response years gained (RYGs) according to the American College of Rheumatology (ACR) criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base-case analysis, average values of costs, response years and QALYs were applied. Costs were in 1998-2001 values (euro 1 approximately equal to $US 0.91, average of the period from the year 2000 through 2001). MAIN OUTCOME MEASURES AND RESULTS: After 3 years, adding leflunomide was less costly and more effective than the strategy excluding leflunomide when total (direct and indirect) costs were considered. There were savings of euro 271,777 and 8.1, 4.3, 5.1 and 4.9 ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively, obtained through adding leflunomide. Focusing on direct costs, adding leflunomide was more costly and more effective compared with excluding leflunomide, with an incremental cost effectiveness of euro 5004 per ACR20RYG, euro 9535 per ACR50RYG, euro 7996 per ACR70RYG, and an incremental cost utility of euro8301 per QALYG, after 3 years. The robustness of the results was shown in comprehensive sensitivity analyses. In the analysis of extremes, different combinations of the limits of cost, effectiveness and utility parameters were investigated. Adding leflunomide to sequential DMARD therapy remained dominant in 79% of the possible cases, i.e. was less costly and more effective than the strategy excluding leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29% and remained more costly and more effective in 50% of possible cases. CONCLUSIONS: Our analysis suggests, with its underlying data and assumptions, that having leflunomide as an additional option in a DMARD treatment sequence extends the time patients benefit from DMARD therapy at reasonable additional direct costs. Adding leflunomide may even be cost saving when total (direct and indirect) costs are considered. As data on DMARD effectiveness were extracted from the results of clinical trials, real-world data from observational studies would be needed to corroborate the findings of the present analysis.

Schädlich PK, Zeidler H, Zink A, Gromnica-Ihle E, Schneider M, Straub C, Brecht JG, Huppertz E. · InForMed GmbH - Outcomes Research and Health Economics, Bureau Itzehoe, Conrad-Roentgen-Strasse 58C, D-25524 Itzehoe, Ingolstadt, Germany. · Pharmacoeconomics. · Pubmed #15853437 No free full text.

Abstract: OBJECTIVE: To quantify direct costs of medication and cost of illness (according to functional capacity) for patients with rheumatoid arthritis (RA) in Germany, allowing further use in a health economic evaluation of sequential therapy with disease-modifying antirheumatic drugs (DMARDs) in specialised, i.e. rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted from the societal perspective in Germany using a modelling approach, which was based on secondary analysis of existing data and on data from a sample of 583 patients from the German rheumatological database of 1998. Functional capacity was defined by the Hannover Functional Ability Questionnaire (HFAQ) scores. Costs were calculated from resources utilised and patients' work capacity. Direct costs consisted of outpatient medical services, inpatient treatment, long-term care and rehabilitation treatment. Indirect costs incurred by sick leave and premature retirement were quantified according to the human-capital approach. MAIN OUTCOME MEASURES AND RESULTS: Average total direct costs (year 1998-2001 values) per patient per year for continuous treatment with the selected DMARDs comprising costs for drugs, monitoring and treatment of adverse drug reactions (ADRs) were highest for intramuscular gold (sodium aurothiomalate) [euro 2106 (euro 1 approximately equal to $US 0.91; average of the period from 2000 through 2001)] followed by leflunomide (euro 2010), azathioprine (euro 1878), sulfasalazine (euro 1190), oral methotrexate (euro 708), and lowest for the antimalarials chloroquine/hydroxychloroquine (euro 684). There were additional yearly costs for RA-related non-DMARD medication of euro 554 per patient, including management of ADRs.Mean cost of illness (year 1998 values) excluding medication cost amounted to euro 17,868 per RA patient per year. Annual costs increased with increasing disability, i.e. decreasing functional capacity, of RA patients from euro 6029 per patient with more than 94% of functional capacity to euro 28,509 per patient with <20% of functional capacity. In general, there was a predominance of indirect costs in each of the categories of functional capacity, ranging between 74% and 87% of total (direct and indirect) annual costs per RA patient. Annual direct costs increased from euro 811 to euro 7438 per patient with increasing disability. Inpatient treatment was the predominant component of direct costs. Patients in the worst category (<20%) of function experienced hospital costs that were 6.5 times higher than those of patients in the best category (>94%). CONCLUSIONS: On the basis of the data presented it can be concluded that the results of this investigation are typical for patients in rheumatological care in Germany and can therefore be used in a health economic analysis of different DMARD sequences aimed at changing disease progression over time.

Mau W, Listing J, Huscher D, Zeidler H, Zink A. · Institute for Rehabilitation Medicine, Martin-Luther University Halle-Wittenberg, Halle, Germany. · J Rheumatol. · Pubmed #15801031 No free full text.

Abstract: OBJECTIVE: To compare labor force participation across chronic inflammatory rheumatic diseases in order to assess the influence of the disease, disease duration, sex, education, and labor market conditions on employment. METHODS: Data from the German rheumatological database on outpatients of working age (20-59 yrs) between 1993 and 2001 were analyzed. The patients had rheumatoid arthritis (RA; n = 26,071), ankylosing spondylitis (AS; n = 5564), psoriatic arthritis (PsA; n = 6041), systemic lupus erythematosus (SLE; n = 4603), systemic sclerosis (SSc; n = 802), or Wegener's granulomatosis (WG; n = 385). Using population data, standardized employment ratios (SER) and part-time employment ratios of observed versus expected cases with 95% CI were calculated by means of indirect standardization for age and year of documentation. RESULTS: Across all diseases the overall employment rates were significantly lower than in the general population. Significant differences in SER were found between the diseases. The lowest SER of 0.76 to 0.81 (1.0 = population) were found in patients with RA, SLE, SSc, and WG. Higher SER were seen in AS (0.94) and PsA (0.92). In patients with a disease duration > 10 years the relative risk of being employed compared to RA, was 1.42 for AS, 1.26 for PsA, and 1.15, 1.03, 0.62 for PsA, SLE, SSc and WG, respectively. Comparing areas with low and high unemployment rates, a highly significant influence of labor market conditions on the SER was observed. The SER were significantly lower in patients with < 10 years of school education. CONCLUSION: Differences between employment rates in the population and the rates for the diseases under study are smaller than assumed by most clinical studies, especially in AS and PsA. However, these differences increase with longer disease duration. Specific measures to prevent patients from losing their job are needed, especially in areas with overall high unemployment.

Zink A, Listing J, Kary S, Ramlau P, Stoyanova-Scholz M, Babinsky K, von Hinueber U, Gromnica-Ihle E, Wassenberg S, Antoni C, Herzer P, Kekow J, Schneider M, Rau R. · German Rheumatism Research Centre, Berlin, Germany. · Ann Rheum Dis. · Pubmed #15708884 links to  free full text

Abstract: OBJECTIVE: To compare drug continuation rates in patients with rheumatoid arthritis who start on a biological agent and in a control group of patients with a change in disease modifying antirheumatic drug (DMARD) treatment after previous DMARD failure. METHODS: Patients with rheumatoid arthritis enrolled in the German biologics register between May 2001 and September 2003 were included in the study. Data were available for 511 patients treated with etanercept, 343 with infliximab, 70 with anakinra, and 599 controls. Propensity scores were used to select a subsample of patients from the control group who were likely to be treated with biological agents because of their disease severity, as well as comparable infliximab and etanercept cases. RESULTS: Treatment continuation after 12 months was similar for etanercept (68.6% (95% confidence interval, 62% to 75%)) and infliximab (65.4% (58% to 73%)) but lower for anakinra (59% (41% to 77%)). Treatment continuation was more likely for patients on combinations of biological agents and DMARDs than for those on infliximab or etanercept alone. Patients treated with biological agents were more severely ill than those in the control group and had more previous DMARD failures. After adjustment for baseline differences, the continuation rates were higher in patients treated with biological agents than in comparable control patients treated with leflunomide or leflunomide/methotrexate. CONCLUSIONS: Treatment continuation of biological agents in clinical practice is less likely than in randomised clinical trials but more likely than in comparable controls treated with conventional DMARDs.

Westhoff G, Listing J, Zink A. · Deutsches Rheuma-Forschungszentrum Berlin, Forschungsbereich Epidemiologie, Schumannstrasse 21/22, 10117 Berlin, Germany. · Z Rheumatol. · Pubmed #15517302 No free full text.

Abstract: We examined out-of-pocket medical expenditures (OoP) of 869 patients with recent onset rheumatoid arthritis (ACR criteria, disease duration <2 years) using data from a prospective observational cohort. Out-of-pocket costs were retrospectively assessed for a period of 6 months by a list of 14 cost domains. Of the patients, 82% had costs due to copayments for prescribed drugs and 56% for over-the-counter drugs. Within six months each patient spent an average of 47 (+/- 67) Euro as co-payment and 45 (+/- 96) Euro for over-the-counter drugs. A comparable sum was spent for complementary and alternative medicine (47+/-250 Euro), which was used by 14% of the patients. The mean total OoP expenditure caused by RA was 628 Euro p.a. (median 306, IQ 66-334 Euro). The median costs accounted for approximately 2% of the average disposable yearly income in Germany. Out-of-pocket spending increased with functional limitations, poor health condition and pain as well as with level of education. A multivariate logistical regression analysis showed that patients with these characteristics spent about twice as much as patients with mild disease or low educational level. The odds ratios for having more than 306 Euro OoP-costs p.a. were OR=2.6 (CI 1.7-4) for patients with severe vs. moderate functional disability (HAQ> or =1.5 vs <1.5), OR=2.4 (CI 1.4-4.4) for patients in poor vs. good health condition (NRS 7-10 vs 0-3), and OR=2.1 for patients with severe vs. mild pain (CI 1.4-3.3). The level of OoP spending also varied by employment status (OR=0.28; CI 0.1-0.6 for jobless vs employed patients). Despite almost universal insurance coverage in Germany, patients with rheumatoid arthritis were exposed to substantial OoP expenditures. As policymakers discuss cost sharing and design of benefit packages to contain health spending, it is important to consider the expenditures that persons with chronic conditions like rheumatoid arthritis already have.

Zink A, Fischer-Betz R, Thiele K, Listing J, Huscher D, Gromnica-Ihle E, Specker C, Schneider M, Anonymous00368. · Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany. · Lupus. · Pubmed #15352425 No free full text.

Abstract: During the past 20 years, outcome studies in the rheumatic diseases have, on the one hand, given increasing evidence of the unfavourable long-term prognosis of rheumatoid arthritis (RA) and on the other hand determined continuous improvement of prognosis in systemic lupus erythematosus (SLE). The aim of the study was to investigate how this translates into the current spectrum of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) seen by rheumatologists in Germany and to compare aspects of the burden of disease, disease outcomes and treatment between these two important rheumatic diseases using a large clinical database. Current health care was analysed with data from the German rheumatological database of 10 068 patients with RA and 1248 patients with SLE seen by rheumatologists in 2001. In addition, of a total of 3546 patients with SLE and 24 969 patients with RA seen at the German Collaborative Arthritis Centres between 1994 and 2001, 3465 cases of SLE were matched by age, sex, disease duration and referral status with a corresponding RA case. There were considerable differences in treatment of patients before referral to a rheumatologist and in rheumatologic care. In 2001, patients with SLE were treated by their rheumatologists mainly with antimalarials (AM, 37%), azathioprine (29%) and nonselective NSAIDs (16%). Of them, 61% received at least one immunosuppressive drug (including AM) plus glucocorticoids. In RA, methotrexate was the predominant medication (63%), and 56% received at least one immunosuppressive drug plus glucocorticoids. Matched pairs analysis showed that SLE patients with a short disease duration were almost equally burdened by pain, functional limitations and reduced health status as RA patients. After a disease duration of >10 years, however, patients with RA showed poorer outcomes than those with SLE: RA patients reported significantly more often severe pain (30% in RA versus 17% in SLE) and poor global health status (52 versus 38%), and their disease activity as well as severity was rated higher by the rheumatologists. In conclusion, comparing large groups of RA and SLE patients we found a similar burden in early but not in late disease. Taking into account limitations as to the generalizability of the results (recruitment in rheumatologic care, cross-sectional data, underestimation of SLE-specific outcomes), the discrepancy between the high increase in disease-related negative outcomes with longer disease duration in RA but not in SLE indicates a better long-term prognosis in SLE concerning the items observed. The great disparity in treatment intensity between rheumatologists and nonrheumatologists shows that the involvement of a specialist is needed equally in both diseases.

Zink A, Huscher D, Thiele K, Listing J, Schneider M. · Forschungsbereich Epidemiologie, Deutsches Rheuma-Forschungszentrum Berlin, Berlin. · Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. · Pubmed #15221101 No free full text.

Abstract: The national database of the German Collaborative Arthritis Centers is a joint venture of German rheumatology. Since 1993, all outpatients with inflammatory rheumatic diseases treated in 1 of 24 arthritis centers have been registered once a year with a clinical record form and a patient questionnaire. The aim is to continuously monitor the current state and trends in rheumatologic health care and to gain knowledge on the outcomes and burdens of diseases as well as medical, social, and economic consequences beyond the limited perspective of randomized controlled trials. Data collected for 10 years about 145,000 patients with inflammatory rheumatic diseases are available making it possible to analyze even very rare diseases with sufficient numbers of cases. Selected results concerning the health care situation in specialized and nonspecialized care, practice variations in rheumatology, and the burden of illness in various diseases are reported.

Minden K, Niewerth M, Listing J, Biedermann T, Schöntube M, Zink A. · Deutsches Rheuma-Forschungszentrum Berlin, Schumannstr. 21/22, 10117 Berlin, Germany. · Ann Rheum Dis. · Pubmed #15194580 links to  free full text

Abstract: OBJECTIVE: To estimate the cost of illness in an incidence based cohort of patients with juvenile idiopathic arthritis. METHODS: Direct costs (healthcare and non-healthcare costs) and indirect costs (productivity loss due to sick leave and work disability) were measured in 215 JIA patients, assessed on an average of 17 years after disease onset. Assessment included a clinical evaluation, a structured interview, and two self completion questionnaires. Annual direct costs were estimated based on the reported use of healthcare services and resources, using average unit prices. Indirect costs were estimated from the number of work days missed-that is, using the human capital approach. RESULTS: The mean total cost of late JIA was estimated to be 3500 per patient and year, of which the direct cost contributed more than half. Patients with still active disease (55%) incurred the major share (90%) of the cost. They had a mean total cost of 5700 per patient year, with those under rheumatological care incurring a cost of 9300. Having a certain JIA subgroup, functional disability, or receipt of specialised care independently contributed to the total cost in active JIA. Highest mean total costs were found in active seropositive polyarthritis (17 000) and extended oligoarthritis (11 000), while the lowest were found in active enthesitis related arthritis (1500) and persistent oligoarthritis (2700). CONCLUSIONS: Estimated 12 month costs in late JIA are considerable, differing among the various JIA subgroups. Treatment strategies in JIA should be analysed for their cost effectiveness in the long term.

Zink A, Huscher D, Anonymous00196. · Epidemiology Unit, German Rheumatism Research Centre, Berlin. · J Rheumatol Suppl. · Pubmed #15053448 No free full text.

Abstract: We describe the aims and uses of a large rheumatological database, the national database of the German Collaborative Arthritis Centres. The database is a continuing registry of all patients with inflammatory rheumatic diseases seen at one of the member sites of the German Collaborative Arthritis Centres. The patients are recorded once a year with a clinical datasheet and a patient questionnaire. The database has been used for identification of deficits and trends in health care, description of current treatment practices, practice variations and individual burden of diseases, as well as for quality assessment. Large differences in disease modifying antirheumatic drug treatment between rheumatologists and nonspecialists as well as deficits in nonmedicinal therapies were identified. Considerable practice variation in German rheumatology with respect to drug and nondrug therapies was identified. The burden of disease (pain, disability, early retirement) was high in various patient subgroups. The database is useful for various aspects of health services research. It has, however, the important limitation that no specific followup procedure is applied. Therefore, longitudinal data exist only for patients in continuing rheumatological care.

Schädlich PK, Zeidler H, Zink A, Gromnica-Ihle E, Schneider M, Straub C, Brecht JG, Huppertz E. · InForMed GmbH-Outcomes Research and Health Economics, Büro Itzehoe, Conrad-Röntgen-Str. 58C, 25524 Itzehoe, Germany. · Z Rheumatol. · Pubmed #14991279 No free full text.

Abstract: 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.

Rudwaleit M, Andermann B, Alten R, Sörensen H, Listing J, Zink A, Sieper J, Braun J. · Rheumatology, University Hospital Benjamin Franklin, Berlin, Germany. · Ann Rheum Dis. · Pubmed #12379517 links to  free full text

Abstract: BACKGROUND: The prevalence of atopic disorders in ankylosing spondylitis (AS) is unknown. AS and rheumatoid arthritis (RA) exhibit divergent T helper (Th) cell cytokine patterns. OBJECTIVE: To test the hypothesis that Th2 polarised atopic disorders may be decreased in Th1 polarised RA but increased in AS, which is characterised by an impaired Th1 cytokine pattern, by assessing the prevalence of atopic disorders in AS and RA. METHODS: 2008 subjects (380 patients with AS, 728 patients with RA, 900 controls) from Berlin, Germany, were considered in this cross sectional study. A questionnaire incorporating questions from the European Community Respiratory Health Service (ECRHS) and the International Study of Asthma and Allergies in Childhood (ISAAC) protocol was mailed to all subjects. Disease severity was assessed by the modified Health Assessment Questionnaire (mHAQ). RESULTS: 1271 (63.3%) people responded to the questionnaire. The prevalence of any atopic disorder was 24.6% (61/248) in patients with AS, 20.7% (111/536) in controls, and 13.1% (64/487) in patients with RA (p=0.0009 for AS v RA; p=0.001 for controls v RA). Hay fever was reported by 40/248 (16.1%) patients with AS, 82/536 (15.3%) controls, and 42/487 (8.6%) patients with RA (p=0.002 for AS v RA; p=0.001 for controls v RA). Atopic dermatitis was reported by 19/248 (7.7%) patients with AS, 26/536 (4.9%) controls, and 14/487 (2.9%) patients with RA (p=0.003 for AS v RA), and asthma by 18/248 (7.3%) patients with AS, 35/536 (6.5%) controls, and 21/487 (4.3%) patients with RA. The differences were related neither to age nor to drugs. Disease severity was less in atopic patients with RA who had the atopic disorder before the onset of RA (median mHAQ 0.75) than in patients in whom RA preceded the atopic disorder (median mHAQ 1.75; p=0.027). CONCLUSIONS: Atopic disorders are decreased in RA but only slightly and non-significantly increased in AS. This may imply that atopy confers some protection from RA but only little if any susceptibility to AS. It may further indicate that the cytokine deviation towards an impaired Th1 pattern in AS is less strong than the cytokine deviation towards Th1 in RA, a finding which may affect future therapeutic approaches.

Minden K, Niewerth M, Listing J, Biedermann T, Bollow M, Schöntube M, Zink A. · German Rheumatism Research Center, Berlin. · Arthritis Rheum. · Pubmed #12355487 links to  free full text

Abstract: OBJECTIVE: To describe the long-term outcome of juvenile idiopathic arthritis (JIA). METHODS: All patients with JIA referred to a pediatric rheumatology center between 1978 and 1988 were identified and invited to undergo an assessment. Patients with JIA from a population-based cohort from East Berlin were included. The outcome assessment considered changes in body function and structure (e.g., mortality, joint abnormalities, disease activity), activities at the individual level (Health Assessment Questionnaire), and participation in society (e.g., mobility, educational and vocational background). RESULTS: Of 260 eligible patients, 215 (83%) were evaluated. Subtypes of JIA at disease onset included oligoarthritis (40%), polyarthritis (14%), systemic arthritis (14%), psoriatic arthritis (1%), enthesitis-related arthritis (15%), and other arthritis (16%). Followup was conducted after a median of 16.5 years. No deaths occurred in this cohort. At followup, approximately half of the patients had active disease and/or changes in body structures to a variable extent. Approximately one-third of patients rated themselves as being functionally limited. Patients demonstrated good social integration: few mobility problems were reported, and the educational achievements of patients were higher and their rate of unemployment was lower compared with the age-matched population. No significant differences in outcome were found between the population-based and the referral-based cohorts. CONCLUSION: Even though approximately half of the JIA patients had more or less distinctive changes in body function and/or structure after a disease duration of >15 years, fewer than 10% were severely disabled or handicapped. Because JIA often persists into adulthood, long-term followup and care are necessary.

Minden K, Niewerth M, Listing J, Zink A, Anonymous00034. · Epidemiology Unit, German Rheumatism Research Center Berlin. · J Rheumatol. · Pubmed #11908581 No free full text.

Abstract: OBJECTIVE: To describe the health care provision for children and adolescents with chronic arthritides in Germany in 1998. METHODS: Data were analyzed from the German pediatric rheumatologic database of the year 1998. It contains clinical and patient questionnaire data for 2488 patients with rheumatic diseases seen at 18 pediatric rheumatology units. RESULTS: A total of 1811 of all patients recorded in the database had chronic arthritides--931 with juvenile chronic arthritis, 86 with juvenile spondyloarthropathy, and 65 with juvenile psoriatic arthritis were considered in the analysis. These patients seen by pediatric rheumatologists had a median age of 10 years and a median disease duration of 4 years. The majority were being treated at pediatric rheumatology disease centers and at universities. Nonsteroidal antiinflammatory drugs were the most commonly used drugs for all forms of chronic arthritides. Almost half the patients with chronic arthritides received disease modifying antirheumatic drugs, with methotrexate the most frequently prescribed agent. While the majority of patients reported having physiotherapy, low prescription rates were noted for comprehensive measures such as occupational therapy and patient education. Only a few patients showed severe functional limitation, 2% of them being rated in Steinbrocker class III or higher. While the patients' functional limitation correlated with disease activity, neither disease duration nor sex, arthritis subgroup nor time span to the first visit at the rheumatology unit had any relevant influence on functional status. CONCLUSION: The data reveal the spectrum of patients with chronic arthritides seen by German pediatric rheumatologists, as well as the treatment patterns of their physicians.

Zink A. · Deutsches Rheuma-Forschungszentrum Berlin Schumannstr. 21/22, 10177 Berlin, Germany. · Z Rheumatol. · Pubmed #11826743 No free full text.

Abstract: The national database of the German Collaborative Arthritis Centres is well-established in German rheumatology as a tool for the observation and assessment of treatments. The usage and spread of new drugs and treatment principles is regularly observed. Discussion about practice variations in treatment contributes to the internal quality assessment in the participating arthritis centres.

Jäckel WH, Beyer WF, Droste U, Engel JM, Genth E, Kohlmann T, Kriegel W, Mau W, Pott HG, Rehberg W, Sangha O, Schmidt K, Wassenberg S, Zink A. · Hochrhein-Institut für Rehabilitationsforschung Bergseestr. 61 79713 Bad Säckingen, Germany. · Z Rheumatol. · Pubmed #11759234 No free full text.

Abstract: By application of a standardized core set of outcome measurement instruments, comparison between studies as well as meta-analyses in rehabilitation research can be facilitated. The German Society for Rheumatology has commissioned its working group on rehabilitation with the development of a proposal for such a core set of outcome measurement instruments. In a first step, dimensions for outcome measurement in rehabilitation were defined by a group of experts which represented rehabilitation hospitals, acute care hospitals, and research groups specialized in outcome measurement. The Delphi method was used in a multiple step consensus process. In a second step, instruments and procedures to operationalize the relevant dimensions were chosen. Reliability, validity, sensitivity to change, and practicability were used as criteria for selecting measurement instruments. The main intention of the proposed core set of outcome measurement instruments is to facilitate the processes of planning and carrying out rehabilitation research studies. Furthermore, the proposed instruments can be used for clinical documentation systems as well as for internal or external quality assurance programs.

Zink A, Listing J, Ziemer S, Zeidler H, Anonymous00390. · Epidemiology Unit, German Rheumatism Research Center, Berlin. · J Rheumatol. · Pubmed #11669156 No free full text.

Abstract: OBJECTIVE: To describe practice variation in the treatment of rheumatoid arthritis (RA) among German rheumatologists with regard to drug and non-drug therapy. METHODS: We used data of 7,326 patients with RA registered in a national German rheumatological database in 1998. In the database, every patient with an inflammatory rheumatic disease seen at one of the German Collaborative Arthritis Centres is registered once a year with a standard clinical data form and a patient questionnaire. We compared health care provided by 29 rheumatological outpatient units. For drug and non-drug treatment unit prescription rates, ranges and outliers were calculated. Logistic regression analysis was used for case mix adjustment and for the identification of practice patterns. RESULTS: We observed variation concerning the frequency of use of single disease modifying antirheumatic drugs (DMARD). The median of the prescription rates in the 29 units for methotrexate (MTX) was 55% in 1998 (1st quartile: 51%, 3rd quartile: 63%); sulfasalazine had a median of 15% (quartiles: 10%/19%), antimalarials a median of 8% (quartiles: 5%/21%). Combination DMARD therapy was used in 11% (quartiles: 6%/18%). Prescriptions of low dose steroids (< or = 7.5 mg) had a median of 45% (quartiles: 35%/55%), and nonsteroidal antiinflammatory drugs (NSAID) had a median prescription rate of 58% (quartiles: 50%/70%). High variation was also found concerning active physiotherapy (median: 41%; quartiles 34%/55%) and passive physical measures (median 14%, quartiles 9%/37%). Differences in case mix (age, sex, rheumatoid factor, disease duration, severity, disability) only explained a small proportion of the total variation. When the units were grouped according to the frequency of prescription of DMARD combination therapy, treatment patterns could be identified. Units with higher rates of DMARD combination therapy used more drugs for the prevention and treatment of osteoporosis, more active physiotherapy but fewer NSAID and fewer passive physical therapies. CONCLUSION: Variation in drug and non-drug treatment indicates significant differences in health care provision. Trends in the drug management of RA are adopted differentially by the members of the rheumatology community. The large variability in non-drug therapies may, apart from differences in availability, suggest a lack of agreement on therapeutic effectiveness.

Westhoff G, Zink A. · Deutsches Rheuma-Forschungszentrum Berlin Schumannstr. 21/22 10117 Berlin. · Z Rheumatol. · Pubmed #11263012 No free full text.

Abstract: Although increased efforts have been made, rheumatoid arthritis still leads to severe disability and dependence on external help in about one-third of the patients. Relatively little is known on how help-dependent RA patients manage everyday life, to what extent they need help, by whom the help is given, what the patients' future help perspectives are and what kind of patient- and resource-related characteristics are associated with unmet need. METHODS: By means of standardized interviews a representative sample of severly disabled RA patients was investigated with respect to present life situation, functional capacity, amount of help needed, relationship of caregiver and patient, health status of caregiver, stability of the help situation, housing preferences and help-seeking behaviour. The patients were classified as being either in definite need of help or independent of external help. RESULTS: Patients with comparable disabilities living on their own had only one-third of the help of those living together with others. They received help slightly more often from non-family caregivers, such as visiting nurses or privately paid household help, than from family members. Although many patients had rather uncertain perspectives for the future, the majority vehemently rejected living in a retirement home or in a home for the disabled. This refusal to live in an institution was independent of functional capacity, adequacy of the present help situation and the financial situation. Unmet need was highly associated with the age and health status of the caregiver as well as the help-seeking behaviour of the dependent person, but not with functional status or available resources. CONCLUSION: Given an appropriate home, the majority of conditions for a self-determined life for help-dependent RA patients are satisfied by the present outpatient help and care systems in Germany, but patients and their care givers need to be encouraged to take advantage of the available help and care facilities.

Zink A, Listing J, Niewerth M, Zeidler H, Anonymous00250. · Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany. · Ann Rheum Dis. · Pubmed #11171679 links to  free full text

Abstract: OBJECTIVE: To describe current treatment of patients with rheumatoid arthritis (RA) in German rheumatology. METHODS: Data from the German rheumatological database of 1998, comprising clinical and patient questionnaire data of 12 992 outpatients with RA seen at 24 collaborative arthritis centres in Germany, were analysed. RESULTS: At the time of documentation, 88% of the patients with RA were undergoing disease modifying antirheumatic drug (DMARD) treatment. Methotrexate (MTX) was prescribed to 56% of the patients (61% with seropositive and 45% with seronegative RA). Combination treatment was used in 15%. MTX was the drug of first choice even in patients with up to one year's disease duration (49%), followed by antimalarial drugs (21%). Patients treated by non-rheumatologists within the previous year had received DMARD treatment in only 33% of the cases. In steroid treatment, low doses (< or = 7.5 mg/day) were used by rheumatologists much more often (44%) than higher doses (12%). 16% of the patients had been inpatients during the previous year, with a median length of stay accumulated over the year of 21 days. Together with stays in inpatient rehabilitation, 22% of all patients had had some form of inpatient treatment. Comprehensive measures such as occupational therapy and patient education were prescribed to fewer than 12% of the patients, mostly during their hospital stay. CONCLUSION: German rheumatologists do follow recent recommendations about early and effective treatment. However, there are still deficits in outpatient care with non-medicinal measures like occupational therapy and patient education, which may partly explain the high hospital admission rates.

Zink A, Listing J, Klindworth C, Zeidler H, Anonymous00249. · Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany. · Ann Rheum Dis. · Pubmed #11171678 links to  free full text

Abstract: OBJECTIVE: To describe the aims, principles, and content of the German rheumatological database and to present data on patient mix and healthcare provision for the year 1998. METHODS: The German rheumatological database contains clinical and patient derived data of the outpatients with inflammatory rheumatic diseases seen at one of the 24 collaborative arthritis centres. The case mix, institutional context, and demographic features of 25 653 patients from the year 1998 were analysed. RESULTS: 51% of the patients had rheumatoid arthritis, 23% seronegative spondyloarthropathies, including ankylosing spondylitis, psoriatic arthritis, and reactive arthritis, and 19% had vasculitis, including SLE (5%). The distribution of the age at onset of patients with RA with < or = 2 years' disease duration was comparable with recent incidence data from population studies. The case mix differed between university departments and rheumatology hospitals as well as individual practices. 65% of the male and 46% of the female patients at ages 18-60 were still in gainful employment, the rates of employment were 14% below the population rates for women, and 11% below those for men. 62% of all patients had seen a rheumatologist within the first year of disease, 73% within the first two years. Ankylosing spondylitis was seen in rheumatological care much later than all other diseases (only 39% within the first year). The mean number of contacts with a rheumatologist was five a year; rheumatologists in individual practices saw their patients seven times a year on the average. Together with visits to the non-specialist doctor mainly treating the patient, the mean number of visits to the doctor for a rheumatic condition was 20 a year. CONCLUSION: Large databases like this one give information about the patient case mix in different healthcare settings, about treatment practice, and about the consequences of disease. Patients treated in specialised rheumatology units in Germany are referred earlier than in the past, which probably reflects better regional cooperation due to the implementation of arthritis centres. University departments and outpatient clinics of rheumatology hospitals contribute considerably to the specialised care of patients with arthritis and connective tissue diseases.

Westhoff G, Listing J, Zink A. · Epidemiology Unit, German Rheumatism Research Centre, Berlin, Germany. · Arthritis Care Res. · Pubmed #11094922 No free full text.

Abstract: OBJECTIVE: The goal of the study was to obtain an estimate of the proportion of patients with rheumatoid arthritis (RA) in rheumatologic care who are unable to live independently. It investigates the association of age, disease duration, disease activity, joint involvement, and comorbidity with dependence on help and care. In addition, we attempt to derive an estimate of the level of physical disability at which dependence on external help is to be expected in more than 50% of the cases. METHODS: A sample of 273 patients with RA and considerable physical disabilities (less than 67% of full functional capacity) was drawn from the Berlin rheumatologic database. Standardized questionnaires and interview data were used to ascertain dependence on help and care. Patients were classified as in need of help when they depended on external help to manage household chores and as in need of care if beyond this they depended on assistance to manage personal hygiene and nutrition. RESULTS: More than 50% of the patients who had less than 58% of full functional capacity (Health Assessment Questionnaire [HAQ] > 1.54) required help, and for patients with less than 30% (HAQ > 2.3) the need for help was almost certain (more than 95%). Generalizing these results to all RA patients treated by rheumatologists in Berlin, 33% were expected to be dependent on external help and 7% to be dependent on care. Even in patients with disease duration < or = 5 years, a rather high expected proportion of help-dependence was found (26%). When single joints were compared, the highest amount of disability resulted from impaired wrists. Our data suggest that the contribution of comorbidity to functional impairment was low, especially in patients in need of help, while patients independent of help reported more frequently that their comorbid condition had an impact on their physical function. CONCLUSION: The results support the importance of identifying high-risk patients and of the employment of a strategy of early therapeutic intervention, since a high degree of dependence on help was observed in patients with short disease duration. As help-dependence is highly influenced by the condition of the wrists, more attention should be paid to the treatment and stabilization of these joints.

Minden K, Kiessling U, Listing J, Niewerth M, Döring E, Meincke J, Schöntube M, Zink A. · Epidemiology Unit, German Rheumatism Research Center Berlin, and the 2nd Children's Hospital, Berlin-Buch. · J Rheumatol. · Pubmed #10990244 No free full text.

Abstract: OBJECTIVE: Evaluation of the course and the prognosis of juvenile chronic arthritis (JCA) and juvenile spondyloarthropathy (JSpA). METHODS: The entire medical histories of 171 patients with JCA or JSpA were reviewed. The study cohort comprised 102 patients with oligoarticular, 17 with systemic, and 24 with polyarticular onset of JCA; 28 patients had a SpA; 91 patients with JCA from a population based cohort were included in that study cohort. The mean period of followup was 7.4 years. The probability of remission was estimated by survival analysis methods (Kaplan-Meier method). RESULTS: After a disease duration of 10 years the highest probability of complete remission was estimated for patients with oligoarticular or systemic onset of JCA (54% and 38%, respectively). In the oligoarthritis group with late onset of JCA, a lower probability of remission was found for the HLA-B27+ patients compared with HLA-B27- patients. Patients with polyarticular onset of JCA had the poorest prognosis, with a significantly lower probability of complete remission (15%) within 10 years, more secondary injuries, and a lower functional capacity at followup. Patients with JSpA showed a 17% probability of remission after a disease duration of 5 years and ranged between the remission rates for oligoarticular and polyarticular JCA. The estimated remission rates for the patients with JCA in the population based cohort and in the whole cohort were quite similar. CONCLUSION: Our data suggest a favorable prognosis for JCA and JSpA in general, but with differences among the subtypes. It seems that more than 50% of the patients with JCA and JSpA reach adulthood with active arthritis and need further rheumatological care.

Listing J, Rau R, Müller B, Alten R, Gromnica-Ihle E, Hagemann D, Zink A. · German Rheumatism Research Center, Berlin, Germany. · J Rheumatol. · Pubmed #10990219 No free full text.

Abstract: OBJECTIVE: To evaluate the prognostic value of HLA-DRB1 antigens, rheumatoid factor (RF), and C-reactive protein (CRP) with the radiographic outcome of rheumatoid arthritis (RA). METHODS: In total, 139 patients with early RA (< 2 years) were followed up. At the end of 3 year treatment with disease modifying antirheumatic drugs (DMARD) HLA genotyping and external radiographic scoring were performed. The time up to the first development of erosive disease [Ratingen radiographic score (RS) > 0, > 5, > 10] was compared by methods of survival analysis. RESULTS: At 4 years' disease duration, DRB1*04 or DRB1*01 positive patients had RS > 0 or > 10 (73% and 27%, respectively) significantly more frequently than DRB1*04 or DRB1*01 negative patients (37% and 7%, respectively). Nearly independently of the genetic predisposition, RF and elevated CRP at the start of DMARD treatment were predictive for erosive RA at 4 years. Elevated CRP (> or = 15 mg/l) increased the probability of erosive RA in DRB1*04 or DRB1*01 positive patients from 64.0% (in patients with CRP < 15 mg/l) to 83.9%, and in DRB1*04 and DRB1*01 negative patients from 18.8% to 70.1%. The corresponding figures for RF+ and RF- patients were 58.2% and 82.5% in HLA predisposed patients and 23.5% and 60.2% in those who were negative for DRB1*04 and DRB1*01. The probability of a RS > 10 was 40.9% for HLA predisposed patients with elevated CRP. In contrast, no case with RS > 10 was found in 43 patients who had neither of these 2 risk factors. CONCLUSION: Our findings support that HLA predisposition plays an important role with regard to radiographic progression. However, this effect is modified by RF serum concentration and disease activity.

Zink A, Braun J, Listing J, Wollenhaupt J. · German Rheumatism Research Center, Department of Internal Medicine, Klinikum Benjamin Franklin, Berlin, Free University. · J Rheumatol. · Pubmed #10743798 No free full text.

Abstract: OBJECTIVE: To describe indicators of disability and handicap in the 2 major inflammatory rheumatic diseases rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and to estimate the burden of illness in terms of functional status, pain, and global well being, as well as with regard to unemployment and early retirement. METHODS: Data from the German rheumatological database on 52,444 patients with RA and 8,776 patients with AS seen at 21 collaborative arthritis centers in Germany between 1993 and 1997 were analyzed. To estimate the burden of the 2 diseases at different biographical phases, age and sex matched groups of patients were compared for functional disability, pain, global assessment of health status, education level, and employment status. RESULTS: For comparable ages, disability in female patients with AS or RA was rated similarly by the physicians (e.g., 61-70 years: 42% severe disability in RA and 44% in AS), whereas men with AS were rated more disabled than men with RA (61-70 years: 35% in RA and 48% in AS). Patients' self-ratings of disability were generally worse for women than for men (age 61-70: women 37% severe disability in RA and 35% in AS, men: 24% in RA and 19% in AS). Pain intensity was rated similarly by women and men with RA and AS at ages < 51 years (33% severe pain at ages 41-50 in men and 34% in women in both diseases). It increased with age in women (> 70 years: 41% severe pain in RA and 44% in AS) and remained stable in men (27% RA and 29% AS > 70 years). At 71.3% the employment rate in AS was clearly higher than in RA (49.5%). There was significant influence of the education level (men 51-60 years with AS: low education 56% employment rate, high education 79%) and the labor market (men 51-55 years with AS: 80% employment rate under good, 59% under bad overall labor market conditions). CONCLUSION: Age and sex matched groups of patients with RA and AS in tertiary rheumatological care show similar amounts of disability, pain, and reduction in well being. Therefore, the offer of comprehensive care and pain management to both groups should be comparable.