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Editorial Effect of anti-tumor necrosis factor on work disability. free! 2007
Verstappen SM, Jacobs JW, Hyrich KL. · No affiliation provided · J Rheumatol. · Pubmed #17985411 links to free full text
This publication has no abstract.
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Review Tight control in the treatment of rheumatoid arthritis: efficacy and feasibility. 2007
Bakker MF, Jacobs JW, Verstappen SM, Bijlsma JW. · University Medical Center Utrecht, Department of Rheumatology & Clinical Immunology, F02.127, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #17934098 No free full text.
Abstract: OBJECTIVE: To evaluate the available evidence on the efficacy and feasibility of the new concept of tight control in randomised trials in patients with rheumatoid arthritis (RA). Tight control is a treatment strategy tailored to the individual patient with RA, which aims to achieve a predefined level of low disease activity or remission within a certain period of time. METHODS: The literature database PubMed was searched and yielded four trials: the FIN-RACo trial, the TICORA study, the BeSt study and the CAMERA study. RESULTS: Tight control resulted in greater improvement and a higher percentage of patients meeting the preset aim of low disease activity or remission when compared to the control intervention. In the FIN-RACo trial, analysing the subset of patients completing the study, 68% in the tight control group achieved remission (DAS28<2.6) verus 41% in the contrast group [corrected] In the TICORA study, 65% of patients in the tight control group versus 16% of the contrast group achieved remission, based on DAS<1.6 (p<0.0001). In the CAMERA study, 50% of patients in the tight control group using a computer decision model achieved remission, versus 37% in the contrast group (p = 0.029). The BeSt study consisted of only tight control groups aimed at a DAS<1.6; remission was achieved in 38-46% of patients. This is higher than the range of remission in earlier trials of 13-36%. CONCLUSION: Tight control aiming for low disease activity or even better still, remission, seems a promising option in treating patients with RA in clinical trials and probably also in daily practice.
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Review Overview of work disability in rheumatoid arthritis patients as observed in cross-sectional and longitudinal surveys. free! 2004
Verstappen SM, Bijlsma JW, Verkleij H, Buskens E, Blaauw AA, ter Borg EJ, Jacobs JW, Anonymous00105. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. · Arthritis Rheum. · Pubmed #15188338 links to free full text
This publication has no abstract.
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Clinical Conference Safety and efficacy of leflunomide in primary Sjögren's syndrome: a phase II pilot study. 2007
van Woerkom JM, Kruize AA, Geenen R, van Roon EN, Goldschmeding R, Verstappen SM, van Roon JA, Bijlsma JW. · Department of Rheumatology & Clinical Immunology, F 02.127, University Medical Center, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #17223657 No free full text.
Abstract: BACKGROUND: For invalidating symptoms in primary Sjögren's syndrome (pSS), there is still a need for easy-to-administer, cost-effective and well-tolerated systemic treatment. Leflunomide (LEF) is structurally unrelated to other immunomodulatory drugs and might be efficacious in pSS, given its characteristic immunoregulatory modes of action. OBJECTIVE: To investigate the safety and efficacy of LEF in pSS in a phase II open-label pilot study. METHODS: 15 patients with pSS with early and active disease received LEF 20 mg once daily for 24 weeks. Tolerability, safety and efficacy of LEF were evaluated every 8 weeks. Additional safety visits were performed every fortnight. RESULTS: Mild gastrointestinal discomfort (including diarrhoea) and hair loss were mainly reported. Five patients developed lupus-like skin lesions on the face, arms or trunk, responding well to topical corticosteroids, nevertheless causing the withdrawal of one patient. Two patients with pre-existing hypertension had to increase dosages of anti-hypertensive drugs. Increased levels of alanine aminotransferase normalised after dose reduction in two patients. A decrease in general fatigue and an increase in physical functioning were observed after 24 weeks. Serum IgG levels decreased from 8 weeks onwards. Schirmer test values increased, not reaching statistical significance, whereas sialometry values did not change. In four of five repeated biopsies, the lymphocytic focus score decreased at the rate of 1 focus/4 mm(2). A remarkable amelioration of leucocytoclastic vasculitis was observed in three patients. CONCLUSIONS: Although the safety profile seems fairly acceptable, the observed indications for efficacy were modest and may be doubtful in justifying a randomised controlled trial of LEF in pSS.
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Clinical Conference A good response to early DMARD treatment of patients with rheumatoid arthritis in the first year predicts remission during follow up. free! 2005
Verstappen SM, van Albada-Kuipers GA, Bijlsma JW, Blaauw AA, Schenk Y, Haanen HC, Jacobs JW, Anonymous00039. · University Medical Centre Utrecht, Department of Rheumatology and Clinical Immunology, PO Box 85500, 3508 GA Utrecht, Netherlands. · Ann Rheum Dis. · Pubmed #15130899 links to free full text
Abstract: OBJECTIVE: To describe the frequency and duration of remission in the Utrecht rheumatoid arthritis cohort of patients followed since diagnosis, and the clinical and treatment characteristics of patients with remission v those without. METHODS: In 1990 the Utrecht rheumatoid arthritis cohort study group started a clinical trial in which patients with recent onset of rheumatoid arthritis (<1 year) were randomised into four treatment groups: hydroxychloroquine (n = 169); intramuscular gold (n = 163); methotrexate (n = 166); and pyramid (n = 64). After two years, rheumatologists were allowed to prescribe any disease modifying antirheumatic drug. Remission was defined as: duration of morning stiffness < or =15 min, mean VAS pain < or =10 mm, Thompson joint score < or =10, and ESR < or =30 mm/h during at least six months. Cox regression analysis was used to determine baseline clinical, demographic, and treatment predictors of remission. RESULTS: Mean follow up duration was 62 months. Thirty six per cent achieved at least one period of remission. Median duration between diagnosis and the first remission period was 15 months for the intramuscular gold group, 18 months for the methotrexate and hydroxychloroquine groups, and 24 months for the pyramid group (NS). Predictors of remission were early response to initial treatment, less pain, rheumatoid factor negativity, and lower joint score at baseline. CONCLUSIONS: After a mean follow up duration of 62 months, only 36% of the patients had fulfilled the remission criteria at least once. A good response to treatment during the first year seems to be independently associated with remission rather than initial treatment alone.
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Clinical Conference The Utrecht experience with different treatment strategies in early rheumatoid arthritis. 2003
Verstappen SM, Jacobs JW, Bijlsma JW, Anonymous00220. · University Medical Center Utrecht, Department of Rheumatology and Clinical Immunology, F02.127, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. · Clin Exp Rheumatol. · Pubmed #14969070 No free full text.
Abstract: Since 1990 the Utrecht Rheumatoid Arthritis Cohort study group has performed several clinical trials on different treatment strategies in early rheumatoid arthritis (RA) patients. From 1990 till 1994, patients were randomly assigned to the pyramid strategy group or the early DMARD group. Patients in the early DMARD group were allocated to one of the three following treatment strategies: strategy I, starting with hydroxychloroquine (HCQ); strategy II, starting with intramuscular gold (iAU); or strategy III, starting with oral methotrexate (MTX). After one year, statistically significant advantages for the early DMARD group compared with the pyramid group were found for disability, pain, joint score, and ESR. The increase in radiological damage did not differ significantly between the two strategy groups. These first year results proved that early introduction of DMARDs is more beneficial than a delayed introduction. After 5 years, however, no prolongation of the clinical advantages in favor of the early DMARD group, as observed after one year, was found. It was found that patients assigned to the pyramid group received more intra-articular injections during the first two years; at the end of this period 75% of them used DMARDs, especially the more aggressive DMARDs. Based on the first year results, all patients were randomly assigned to one of the three treatment strategies in the early DMARD group between 1994 and 1998. Patients who started with MTX or iAU as the first DMARD demonstrated better results regarding clinical efficacy and radiological damage after 2 years. However, more patients who received iAU therapy had to discontinue their therapy compared with patients who took MTX. We therefore conclude that MTX is the DMARD of first choice and that treatment should be tailored to the individual patient.
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Clinical Conference Five-year followup of rheumatoid arthritis patients after early treatment with disease-modifying antirheumatic drugs versus treatment according to the pyramid approach in the first year. free! 2003
Verstappen SM, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, Borg EJ, Hofman DM, van der Veen MJ, Anonymous00035. · University Medical Center Utrecht, Utrecht, The Netherlands. · Arthritis Rheum. · Pubmed #12847672 links to free full text
Abstract: OBJECTIVE: To evaluate whether the clinical advantages observed after 1 year in a randomized controlled clinical trial, in which 2 treatment strategies were compared (the early disease-modifying antirheumatic drug [DMARD] approach versus the pyramid approach), persist after 5 years. METHODS: In this study, 238 patients with recently diagnosed rheumatoid arthritis (RA) were randomized to either the pyramid group (n = 56) or the early DMARD group (n = 182). Patients assigned to the pyramid group received nonsteroidal antiinflammatory drugs for at least 1 year after inclusion (the mean +/- SD lag time until first prescription of a DMARD was 14 +/- 9 months). Patients in the early DMARD group were treated with a DMARD immediately after inclusion. RESULTS: After 5 years, data were available for 44 patients in the pyramid group (79%) and 145 patients in the early DMARD group (80%). No prolongation of the clinical advantages in favor of the early DMARD group, as observed after the first year, was demonstrated. Nevertheless, a significantly shorter delay time until complete response and a higher number of patients with overall clinically relevant improvement at several assessment points were observed in the early DMARD group compared with the pyramid group. CONCLUSION: The clinical results in favor of the early DMARD group, as observed after the first year, were not as evident after 5 years. This indicates that a more aggressive treatment approach in early RA is required, and that treatment should be continued for a prolonged period of time, in order to maintain the advantages obtained in the first year.
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Article Functional Health Assessment Questionnaire (HAQ) and Psychological HAQ Are Associated with and Predicted by Different Factors in Rheumatoid Arthritis. 2007
Verstappen SM, Jacobs JW, Huisman AM, van Rijthoven AW, Sokka T, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. · J Rheumatol. · Pubmed #17787050 No free full text.
Abstract: OBJECTIVE: To evaluate the association between clinical, demographic, and psychological factors and the functional Health Assessment Questionnaire (HAQ) and psychological HAQ (PSHAQ) in patients with rheumatoid arthritis (RA). METHODS: After a mean followup time of 7 years after diagnosis, 112 patients with RA were asked to fill out the HAQ and the PSHAQ. Several clinical variables [erythrocyte sedimentation rate (ESR), visual analog scale (VAS) pain, VAS general well-being, Thompson joint score, and morning stiffness] had been assessed at diagnosis and at followup. In addition, the Impact of Rheumatic diseases on General health and Lifestyle questionnaire, comprising different domains of psychological distress, was assessed at diagnosis. Spearman correlations were calculated to determine associations between functional HAQ and clinical and psychological variables at baseline and to determine the associations between clinical variables and the HAQ and PSHAQ score at followup. Univariate logistic regression analyses were performed to identify possible predictors at diagnosis for a worse HAQ score and PSHAQ score (score > 1) at followup. RESULTS: At followup the functional HAQ score was associated with all clinical variables, whereas the PSHAQ was only associated with more subjective patient related variables (VAS pain, VAS general well-being, and morning stiffness). The final model of the multivariate regression analyses to predict a worse HAQ score at followup only included worse functional ability [odds ratio (OR) 2.63, 95% confidence interval (CI) 1.30-5.32, p = 0.007]. Anxiety (OR 1.13, 95% CI 1.03-1.24, p = 0.007) and a lower ESR value (OR 0.98, 95% CI 0.96-1.00, p = 0.05) assessed at diagnosis were included into the final model as predictors for a high PSHAQ score. CONCLUSION: Overall, the HAQ score, reflecting limitations of daily functioning, is a good representation of disease activity at diagnosis and after a mean disease duration of 7 years, whereas PSHAQ is not.
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Article Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). 2007
Verstappen SM, Jacobs JW, van der Veen MJ, Heurkens AH, Schenk Y, ter Borg EJ, Blaauw AA, Bijlsma JW, Anonymous00161. · University Medical Center Utrecht, Utrecht, the Netherlands. · Ann Rheum Dis. · Pubmed #17519278 No free full text.
Abstract: BACKGROUND: To investigate whether intensive treatment with methotrexate (MTX) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis. METHODS: In a two-year multicentre open label strategy trial, 299 patients with early rheumatoid arthritis were randomly assigned to the intensive strategy group or the conventional strategy group. Patients in both groups received MTX, the aim of treatment being remission. Patients in the intensive treatment group came to the outpatient clinic once every month; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria, using a computerised decision program. Patients of the conventional strategy group came to the outpatient clinic once every three months; they were treated according to common practice. Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses. RESULTS: Seventy six (50%) patients in the intensive strategy group achieved at least one period of remission during the two year trial, versus 55 patients (37%) in the conventional strategy group (p = 0.03). Areas under the curve for nearly all clinical variables were significantly lower-that is, there was a better clinical effect for the intensive treatment group compared with the conventional treatment group. CONCLUSION: The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX, aiming for remission, tailored to the individual patient. Furthermore, participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice.
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Article QUEST-RA: quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries. 2007
Sokka T, Kautiainen H, Toloza S, Mäkinen H, Verstappen SM, Lund Hetland M, Naranjo A, Baecklund E, Herborn G, Rau R, Cazzato M, Gossec L, Skakic V, Gogus F, Sierakowski S, Bresnihan B, Taylor P, McClinton C, Pincus T, Anonymous00159. · Arkisto/Tutkijat, Jyvaskyla Central Hospital, 40620 Jyvaskyla, Finland. · Ann Rheum Dis. · Pubmed #17412740 No free full text.
Abstract: OBJECTIVE: To conduct a cross-sectional review of non-selected consecutive outpatients with rheumatoid arthritis (RA) as part of standard clinical care in 15 countries for an overview of the characteristics of patients with RA. METHODS: The review included current disease activity using data from clinical assessment and a patient self-report questionnaire, which was translated into each language. Data on demographic, disease and treatment-related variables were collected and analysed using descriptive statistics. Variation in disease activity on DAS28 (disease activity score on 28-joint count) within and between countries was graphically analysed. A median regression model was applied to analyse differences in disease activity between countries. RESULTS: Between January 2005 and October 2006, the QUEST-RA (Quantitative Patient Questionnaires in Standard Monitoring of Patients with Rheumatoid Arthritis) project included 4363 patients from 48 sites in 15 countries; 78% were female, >90% Caucasian, mean age was 57 years and mean disease duration was 11.5 years. More than 80% of patients had been treated with methotrexate in all but three countries. Overall, patients had an active disease with a median DAS28 of 4.0, with a significant variation between countries (p<0.001). Among 42 sites with >50 patients included, low disease activity of DAS28 <or=3.2 was found in the majority of patients in seven sites in five countries; in eight sites in five other countries, >50% of patients had high disease activity of DAS28 >5.1. CONCLUSIONS: This international multicentre cross-sectional database provides an overview of clinical status and treatments of patients with RA in standard clinical care in 2005-6 including countries that are infrequently involved in clinical research projects.
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Article Trends in economic consequences of rheumatoid arthritis over two subsequent years. free! 2007
Verstappen SM, Jacobs JW, Kruize AA, Ehrlich JC, van Albada-Kuipers GA, Verkleij H, Buskens E, Bijlsma JW. · University Medical Center Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #17337750 links to free full text
Abstract: OBJECTIVE: To examine changes in direct costs and in working status over 2 yrs in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: In both 1999 and 2000, RA patients (n = 461) filled out a questionnaire retrospectively regarding utilization of health care, other RA-related direct costs and working status. Patients were categorized into four disease duration groups: 0-2 yrs, 2-6 yrs, 6-10 yrs and >10 yrs. At the same time points, disease activity was assessed. Logistic regression analyses were performed to identify a possible association between disease activity (high >66th percentile) measured at start of the second year and high direct costs (high >66th percentile) in the second year. RESULTS: Compared with the first year, a significant decrease in the costs for contacts with health care workers and for costs for laboratory tests was observed in the second year for the <2 yrs group. In the 2-6 yrs group and the >10 yrs group, we found a significant decrease in costs for devices and adaptations, but medication costs increased in the <2 yrs and the >10 yrs group in the second year. In the >10 yrs group, this was mainly due to an increasing number of patients who started to use biological agents during the second year. In all four disease duration groups, worse Visual Analogue Scale (VAS) disease activity and VAS general well-being were significantly associated with high direct costs. Of 97 patients working without disability at time of the first assessment, 12 (12%) patients became (partial) work disabled during follow-up. CONCLUSION: In particular, costs for devices/adaptations and for medication changed during follow-up. The latter was probably due to an increase in the use of biological agents. Hopefully a decrease in direct costs and a reduced percentage of patients getting work disabled by better disease control will outweigh the high costs of biological drugs in the future.
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Article Utility and direct costs: ankylosing spondylitis compared with rheumatoid arthritis. 2007
Verstappen SM, Jacobs JW, van der Heijde DM, van der Linden S, Verhoef CM, Bijlsma JW, Boonen A. · University Medical Center Utrecht, Department of Rheumatology & Clinical Immunology, F02.127, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #17172249 No free full text.
Abstract: OBJECTIVES: To compare utility and disease-specific direct costs between patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) in the Netherlands. METHODS: Patients with AS and those with RA completed questions on disease characteristics, the EuroQol-5D (EQ-5D) to assess utility, and questionnaire resource utilisation. Resource utilisation was assessed prospectively in AS, but retrospectively in RA. True cost estimates (2003) were used to calculate the costs. Differences in disease characteristics between AS and RA were described, and determinants of EQ-5D utility and costs were explored by Cox proportional hazard regressions. RESULTS: 576 patients with RA and 132 with AS completed the questionnaires. EQ-5D utility (0.63 vs 0.7) was lower, and annual direct costs higher in RA (euro5167 vs euro2574). In multivariate Cox proportional hazard regressions, there was no difference in utility between the diagnostic groups, but patients with RA incurred higher direct costs after controlling for age, gender and disease duration. CONCLUSIONS: In patients with RA and patients with AS, who are under the care of a rheumatologist, utility is equally reduced, but healthcare costs are higher in RA after controlling for age, gender and disease duration. These data can be helpful to provide insights into the differences and similarities between the healthcare needs of both patient groups and to identify issues for further research and for policy in healthcare organisations.
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Article Are glucocorticoids DMARDs? 2006
Bijlsma JW, Hoes JN, Van Everdingen AA, Verstappen SM, Jacobs JW. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Box 85 500, 3508 GA Utrecht, The Netherlands. · Ann N Y Acad Sci. · Pubmed #16855154 No free full text.
Abstract: Disease modifying antirheumatic drugs (DMARDs) are drugs used in rheumatoid arthritis (RA) to control the disease and to limit joint damage and improve long-term outcome. The last decade evidence has accumulated that suggests that low dosages of glucocorticoids are indeed able to control the disease and limit the destruction. This role is especially present in early disease and in combination with other drugs. The evidence is carefully evaluated and discussed. The ultimate conclusion is that indeed glucocorticoids are DMARDs and are especially useful in early RA.
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Article Joint surgery in the Utrecht Rheumatoid Arthritis Cohort: the effect of treatment strategy. 2006
Verstappen SM, Hoes JN, Ter Borg EJ, Bijlsma JW, Blaauw AA, van Albada-Kuipers GA, van Booma-Frankfort C, Jacobs JW. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, F02.127, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #16679433 No free full text.
Abstract: OBJECTIVE: To investigate the prevalence and prognostic factors of joint surgery in a large cohort of patients with rheumatoid arthritis, whose treatment, clinical and radiographic data have been assessed at predefined points in time since disease onset. METHODS: Data on surgical interventions were retrospectively obtained from 482 patients with rheumatoid arthritis whose follow-up data for at least 2 years were available, including treatment and response to treatment during the first 2 years. Survival time until the first surgical intervention and until the first major surgical intervention was determined for the total study population by Kaplan-Meier survival curves. Three separate Cox regression analyses were carried out to determine which variables measured at baseline, during the first year and during the first 2 years were predictors for joint surgery. RESULTS: 27% of the patients underwent surgical interventions. Mean survival time until the first surgical intervention was 10.4 years. The percentage of patients with a surgical intervention was 10% lower in the group with response to treatment when compared with the non-response group. Next to a delayed start with disease-modifying antirheumatic drugs, fast radiographic progression during the first year and first 2 years was a predictor of joint surgery in the multivariate regression analyses. CONCLUSION: Treatment with disease-modifying antirheumatic drugs immediately after diagnosis results in less joint surgery when compared with a delayed start. Furthermore, joint surgery is carried out more often in patients who do not respond to treatment.
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Article Followup radiographic data on patients with rheumatoid arthritis who participated in a two-year trial of prednisone therapy or placebo. free! 2006
Jacobs JW, van Everdingen AA, Verstappen SM, Bijlsma JW. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. · Arthritis Rheum. · Pubmed #16645970 links to free full text
Abstract: OBJECTIVE: In a previous clinical trial of patients with early rheumatoid arthritis (RA), it was determined that patients who received 10 mg of prednisone per day for 2 years had less radiographic joint damage compared with those who received placebo. Our goal was to investigate whether this beneficial effect persisted after the end of the trial. METHODS: A blinded assessment of radiographic joint damage was performed approximately 3 years after the end of the original 2-year study. Twenty-four patients from the original prednisone group (60%) and 28 patients from the original placebo group (68%) participated in this followup study. At the end of the original trial, prednisone dosages were tapered down in the prednisone group and stopped, if possible. Patients from the original prednisone group took prednisone during 35% of the followup period (approximately 1 year) at a mean daily dose of approximately 5 mg. Two patients from the original placebo group started taking prednisone during followup. Radiographs of the hands and feet were scored according to the van der Heijde modification of the Sharp method. RESULTS: During 3 additional years of followup, radiographic scores showed significantly less progression in the original prednisone group than in the original placebo group. Radiographic damage in the original prednisone group did not show an accelerated rate of progression during the followup period. CONCLUSION: The inhibition of radiographic joint damage in patients with early active RA treated with 10 mg of prednisone per day for 2 years seems to persist after the end of prednisone therapy.
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Article Radiographic joint damage in rheumatoid arthritis is associated with differences in cartilage turnover and can be predicted by serum biomarkers: an evaluation from 1 to 4 years after diagnosis. free! 2006
Verstappen SM, Poole AR, Ionescu M, King LE, Abrahamowicz M, Hofman DM, Bijlsma JW, Lafeber FP, Anonymous00302. · Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, The Netherlands. · Arthritis Res Ther. · Pubmed #16507130 links to free full text
Abstract: INTRODUCTION: The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA). METHODS: Clinical and radiographic data of 87 RA patients were recorded 1 year after disease onset and then annually up to four years. Serum concentrations of four cartilage biomarkers were determined at these time points: a neoepitope formed by collagenase cleavage of type II collagen (C2C), a neoepitope formed by collagenase cleavage of type II collagen as well as type I collagen (C1,2C), a carboxy propeptide of type II procollagen formed during synthesis (CPII), and a cartilage proteoglycan aggrecan turnover epitope (CS846-epitope). Biomarker concentrations between patients with rapid radiographic progression (>7.3 Sharp/van der Heijde units per year) and those with slow radiographic progression (<2.3 units per year) were compared. In addition, we evaluated the long-term and short-term predictive value of each biomarker for progression of radiographic damage. RESULTS: Patients with rapid radiographic progression had higher C2C, higher C1,2C, and higher CS846-epitope levels than slow progressors. CPII levels showed no differences. Most importantly, the long-term radiographic progression for C2C, for C1,2C, and for CS846-epitope can be predicted by the biomarker value at year 1 after disease onset. C2C was also a predictor for joint space narrowing and annual radiographic damage during the subsequent year. CONCLUSION: This study shows that the concentration of serum biomarkers of cartilage collagen breakdown and proteoglycan turnover, but not of collagen synthesis, are related to joint destruction in RA. The use of these biomarkers may be of value when studying progression of joint damage in patients with RA.
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Article Productivity costs among patients with rheumatoid arthritis: the influence of methods and sources to value loss of productivity. free! 2005
Verstappen SM, Boonen A, Verkleij H, Bijlsma JW, Buskens E, Jacobs JW, Anonymous00001. · University Medical Centre Utrecht, Department of Rheumatology and Clinical Immunology, F02.127, PO Box 85500, 3508 GA Utrecht, Netherlands. · Ann Rheum Dis. · Pubmed #15860510 links to free full text
Abstract: OBJECTIVE: To assess productivity costs incurred by rheumatoid arthritis, comprising paid as well as household productivity costs, from a societal perspective, using different methods. METHODS: A questionnaire on productivity, including items of the Health and Labour Questionnaire, was completed by 576 patients with rheumatoid arthritis (mean disease duration seven years). The friction cost (FC) method using the gross national wage per hour was applied to estimate paid productivity, and the market equivalent was used to value loss of household productivity. Sensitivity analyses to estimate paid productivity costs among patients of working age included the human capital (HC) method and an alternative source, namely the "added value", to value loss of paid productivity. RESULTS: In the total study population, mean (SD) annual costs from loss of paid productivity according to the FC method were estimated to be 278 (1,559) and mean annual household productivity costs were 2,045 (3,882). When using the HC method, mean annual costs increased to an average of 4,434 (9,957). When using the added value of production, average FC costs increased from 455 to 540 among patients of working age. CONCLUSIONS: Costs from loss of household productivity in rheumatoid arthritis were seven times higher than costs from loss of paid productivity, assessed by the FC method. The high paid productivity costs when using the HC method reflect the high work disability rate in rheumatoid arthritis. As the method of measuring and source of valuing productivity loss has an important influence on the costs, a consensus to standardise these issues is desirable.
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Article Working status among Dutch patients with rheumatoid arthritis: work disability and working conditions. free! 2005
Verstappen SM, Boonen A, Bijlsma JW, Buskens E, Verkleij H, Schenk Y, van Albada-Kuipers GA, Hofman DM, Jacobson JW, Anonymous00039. · University Medical Center Utrecht, Department of Rheumatology and Clinical Immunology, F02.127, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #15454630 links to free full text
Abstract: OBJECTIVES: To assess work disability and variables associated with work disability among Dutch patients with rheumatoid arthritis (RA). METHODS: A questionnaire on working status was filled out by 296 patients of working age. Employment and work disability rates adjusted for age and sex from the Dutch population were determined using indirect standardization. Cox proportional hazard analysis was used to assess baseline predictors of work disability in a subgroup of patients (n = 195). RESULTS: After a mean disease duration of 4.3 yr, patients had a 0.78 (95% CI 0.67-0.88) chance of being employed and a 2.14 (95% CI 1.75-2.54) risk of being work disabled when compared with the Dutch population. Functional disability and job type at the start of the disease were predictors of future work disability. In total, 48 (37%) currently employed patients had changed their working conditions, of which reduced working hours (46%), reduced pacing of work (42%) and help from colleagues (49%) were the most important alterations. Of the 60 work disabled patients without a paid job, only 11 patients (18%) would be willing to work again. CONCLUSION: This study shows that the adjusted employment rates were lower and that work disability rates were higher in patients with RA when compared with the general Dutch population. In addition, a substantial number of employed patients had to change their working conditions due to RA. Only a minority of work disabled RA patients was willing to return to the paid labour force.
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Article Determinants of direct costs in Dutch rheumatoid arthritis patients. free! 2004
Verstappen SM, Verkleij H, Bijlsma JW, Buskens E, Kruize AA, Heurkens AH, Van Der Veen MJ, Jacobs JW. · University Medical Center Utrecht, Department of Rheumatology and Clinical Immunology, F02.127, PO Box 85500, 3508 GA Utrecht, The Netherlands. · Ann Rheum Dis. · Pubmed #15194577 links to free full text
Abstract: OBJECTIVES: To estimate annual direct costs in four distinct disease duration groups (0 to < or =2, 2 to < or =6, 6 to < or =10, and >10 years) of patients with rheumatoid arthritis (RA), to determine predictors of high costs and to describe characteristics of patients with high and with low costs. METHODS: A questionnaire assessing RA related care and resource utilisation rates and costs was completed by 615 RA patients. Predictive variables for incurred costs, as observed during the first year after disease onset, were determined in a subgroup of patients (n = 347). RESULTS: Mean (median) annual direct costs for the four groups with increasing disease duration were respectively: 5235 (2923) Euros, 3930 (1968) Euros, 4664 (1952)Euros, and 8243 (3778) Euros, (p < 0.05). During the first 2 years of the disease total direct costs comprised mainly of consultations with healthcare workers (28%). After 10 years, devices and adaptations were the main contributors (40%) to total costs. Positive rheumatoid factor results at the time of diagnosis and deterioration of functional disability in the first year of disease were predictors of high costs later on in the course of the disease. CONCLUSION: Annual direct costs among patients with a disease duration of less than 2 years tend to be lower among patients with a disease duration of between 2 and 10 years than among patients with a disease duration of more than 10 years. In addition, the proportional distribution of different cost categories to total costs increases with with increasing disease duration.
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