Rheumatoid Arthritis: Boonen A

Boonen A, Landewé R. · No affiliation provided · Ann Rheum Dis. · Pubmed #15647423 links to  free full text

This publication has no abstract.

Boonen A, van der Heijde D. · Division of Rheumatology, Department of Internal Medicine, University Hospital Maastricht Care and Public Health Research Institute, University Maastricht, P. Debyelaan 25, PO Box 5800, 6202 AZ Maastricht, The Netherlands. · Rheum Dis Clin North Am. · Pubmed #16287591 No free full text.

Abstract: This article reviews radiographic data from six cohorts of patients with early inflammatory arthritis. Of the patients, 8% to 15% had erosive disease at the first encounter with the rheumatologist. Classic scoring methods were applied to quantify damage, but baseline damage was low in early inflammatory arthritis. Yearly progression in damage score was assessed only in patients with high suspicion of rheumatoid arthritis at baseline or who had a final diagnosis of rheumatoid arthritis at follow-up and varied between 0.5% and 1.7% of the maximal damage of the scoring method per year. The large number of patients with zero values for erosions and lower progression rates will influence sample sizes in clinical trials in early inflammatory arthritis when including radiographic change as an outcome.

Ortiz Z, Shea B, Garcia Dieguez M, Boers M, Tugwell P, Boonen A, Wells G. · Academia Nacional de Medicina de Buenos Aires, Argentina. · J Rheumatol. · Pubmed #9918266 No free full text.

Abstract: To review the available evidence that has used generic instruments alone or in comparison with disease specific instruments. A systematic review was carried out using the methods recommended by the Cochrane Collaboration. We used MEDLINE and EMBASE searches and we performed a hand search of the abstracts listed under "quality of life" at American College of Rheumatology (ACR) meetings. Selection was limited to randomized controlled trials (RCT) using generic instruments in populations older than 18 years with any of the following diseases: rheumatoid arthritis, fibromyalgia, osteoporosis, osteoarthritis, systemic lupus erythematosus, and ankylosing spondylitis. Language was restricted to English papers. Studies using only disease-specific instruments were excluded. From 488 articles retrieved, 13 reports of 10 randomized controlled trials were selected. There were 101 abstracts on quality of life in ACR abstract books; 78 abstracts contained data on generic instruments, and of these, 9 described their use in RCT. Despite a substantial increase in the number of papers and abstracts addressing different aspects of generic questionnaires, the majority of the papers were descriptive. The evidence is not yet available to document that any of the generic instruments pass the requirements of the OMERACT Filter.

Korthals-de Bos I, Van Tulder M, Boers M, Verhoeven AC, Adèr HJ, Bibo J, Boonen A, Van Der Linden S. · Institute for Research in Extramural Medicine, VU University Medical Center, Amsterdam, The Netherlands. · J Rheumatol. · Pubmed #15338488 No free full text.

Abstract: OBJECTIVE: To describe the effect of indirect costs for patients with early rheumatoid arthritis (RA) within the COBRA trial (Combinatietherapie Bij Reumatoide Artritis) on the cost-effectiveness of both therapies. Analyses of the efficacy and direct costs of the treatments have already been reported. METHODS: Patients with early RA selected for the 56-week trial were randomly assigned to prednisolone, methotrexate, and sulfasalazine (the COBRA combination) (n = 76, tapered after 28 weeks) or to sulfasalazine (SSZ; n = 79, of which 78 patients were evaluable) alone. The main efficacy outcomes were a pooled index and radiographic damage score in hands and feet, and utilities. Direct and indirect costs were measured (from a societal perspective) by means of cost diaries and interviews completed by patients during the intervention phase and the followup phase, each lasting 28 weeks. Differences in mean costs between groups and cost-utility ratios were evaluated by applying nonparametric bootstrapping techniques. RESULTS: In the first 28 weeks, indirect costs per patient totaled US $2,578 and US $3,638 for COBRA and SSZ therapy, respectively (p = 0.09). The total costs were $5,931 and $7,853, respectively (p < 0.05). These differences were lost in the second 28 weeks. For the total period the mean total costs per patient were $10,262 and $12,788, respectively (p = 0.11). Sensitivity analyses showed robustness of the data. The point estimate of the cost per quality-adjusted life-year based on the rating scale was negative at $-385, suggesting dominance of COBRA (more effect at lower cost). CONCLUSION: COBRA therapy adds additional disease control (improvements in disease activity, physical function, and rate of damage progression) at lower or equal cost compared to SSZ in early RA.

Garnero P, Landewé R, Boers M, Verhoeven A, Van Der Linden S, Christgau S, Van Der Heijde D, Boonen A, Geusens P. · INSERM Research Unit 403, and Synarc, Lyon, France. · Arthritis Rheum. · Pubmed #12428224 links to  free full text

Abstract: OBJECTIVE: The known risk factors for radiologic progression in rheumatoid arthritis (RA) are not optimally discriminative in patients with early disease who do not have evidence of radiologic damage. We sought to determine whether urinary C-terminal crosslinking telopeptide of type I (CTX-I) and type II (CTX-II) collagen (markers of bone and cartilage destruction, respectively) are associated with long-term radiologic progression in patients with early RA. METHODS: This was a prospective study of 110 patients with early RA who were participating in the COBRA (Combinatietherapie Bij Reumatoïde Artritis) clinical trial and followup study, a randomized controlled trial comparing the efficacy of oral pulse prednisolone, methotrexate, plus sulfasalazine with sulfasalazine alone. We investigated the relationship between baseline levels of urinary CTX-I and CTX-II and the mean annual progression of joint destruction over a median of 4 years, as measured by changes in the modified Sharp score (average of 2 independent readers). RESULTS: In multivariate logistic regression analysis, baseline urinary CTX-I and CTX-II levels in the highest tertile were the strongest predictors of radiologic progression (Sharp score increase >2 units/year; odds ratio 7.9 and 11.2, respectively), independently of treatment group, erythrocyte sedimentation rate (ESR), Disease Activity Score in 28 joints, rheumatoid factor (RF), and baseline joint damage (Sharp score). The likelihood ratios for a positive test were 3.8 and 8.0 for CTX-I and CTX-II, respectively, which compared favorably with the likelihood ratios for the ESR (3.0), baseline joint damage (1.6), and RF (1.8). When patients were grouped according to the presence (Sharp score >/=4, n = 49) and absence (Sharp score <4, n = 61) of joint damage at baseline, CTX-I and CTX-II levels were predictive only in those without baseline joint damage (odds ratio 14.9 and 25.7, respectively). CONCLUSION: High baseline levels of urinary CTX-I and CTX-II independently predict an increased risk of radiologic progression over 4 years in patients with early RA, especially those without radiologic joint damage. Urinary CTX-I and CTX-II may be useful for identifying individual RA patients at high risk of progression very early in the disease, before erosions can be detected radiographically. Such patients may be in special need of treatments that inhibit bone and cartilage degradation.

Bruynesteyn K, Van Der Heijde D, Boers M, Verhoeven A, Boonen A, Van Der Linden S, Anonymous00326. · University of Maastricht, Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #12382303 links to  free full text

Abstract: OBJECTIVE: In rheumatoid arthritis (RA) in the context of a drug trial, prevention of erosions in undamaged joints is often considered more important than prevention of progression in already damaged joints, although a clear rationale is lacking. The aim of this study is to evaluate the relative contribution of separate components of the erosion score of the modified Sharp/van der Heijde method in early RA. METHODS: Different aspects of erosive damage were evaluated by their ability to discriminate between the 2 treatments in an early RA trial (the COBRA trial). RESULTS: The contribution of progression of already eroded joints to the total erosion score clearly increased during the 1.5 years of the trial. When the periods 0-28, 28-56, and 56-80 weeks were analyzed separately, the erosion score showed a significant difference between the groups in the first 2 periods (P < 0.0001, P < 0.03, and P < 0.64, respectively). Similar differences were seen in rates of progression in previously eroded joints (P = 0.005, P = 0.003, P = 0.35). On the other hand, rates of progression in newly eroded joints showed no significant difference between the 2 treatment groups in the second and third period (P < 0.0001, P < 0.16, P < 0.87). Analyses on joint and patient level showed analogous results. CONCLUSION: Subanalyses on progression rates in noneroded joints and already eroded joints can provide additional information. However, important information and discriminative strength may be lost when assessment is limited to the development of erosions in undamaged joints.

Landewé RB, Boers M, Verhoeven AC, Westhovens R, van de Laar MA, Markusse HM, van Denderen JC, Westedt ML, Peeters AJ, Dijkmans BA, Jacobs P, Boonen A, van der Heijde DM, van der Linden S. · Department of Internal Medicine/Rheumatology, PO Box 5800, University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #11840436 No free full text.

Abstract: OBJECTIVE: The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome. METHODS: All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline). RESULTS: At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28. CONCLUSION: An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.

Lassere M, Boers M, van der Heijde D, Boonen A, Edmonds J, Saudan A, Verhoeven AC. · Department of Rheumatology, St. George Hospital, Sydney, NSW, Australia. · J Rheumatol. · Pubmed #10090192 No free full text.

Abstract: Omeract IV started a discussion on the development of radiological response criteria in rheumatoid arthritis (RA). Such criteria depend on the definition of what constitutes the minimum clinically important progression of damage. Because such a definition is currently not available, as a first step we have used the concept of random measurement error to determine what is the smallest detectable difference (SDD) in radiological progression between 2 radiographs of a particular patient. Baseline and 12 month radiographs (hands, wrists, feet) of 52 patients representative of the spectrum of radiological progression were selected from a randomized controlled trial of early rheumatoid arthritis (COBRA study) and were read paired and chronologically by 2 observers using the van der Heijde modified Sharp method (0-448 scale) and another 2 observers using the Scott modified Larsen method (0-200). The measurement error of progression was determined using the metric 95% limits of agreement method of Bland and Altman. In the setting of early RA the SDD is 11 modified Sharp score units and 8 modified Larsen score units if there is an equal distribution of baseline damage and progression in the sample and the mean score of the same trained observers is always used. The SDD is 15.5 modified Sharp score units and 11 modified Larsen score units if there is an equal distribution of baseline damage and progression in the sample and the mean score of any 2 trained observers is used. Other SDD were determined depending on the context of measurement. Although this exercise needs repetition in other settings, the SDD is a useful starting point in the development of radiological response criteria.

Halvorsen EH, Haavardsholm EA, Pollmann S, Boonen A, van der Heijde D, Kvien TK, Molberg Ø. · Institute of Immunology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway. · Ann Rheum Dis. · Pubmed #18723564 No free full text.

Abstract: BACKGROUND: Peptidylarginine deiminase 4 (PAD4) may generate epitopes targeted by anticitrullinated protein antibodies in rheumatoid arthritis (RA). A subset of patients with RA has serum autoantibodies to human recombinant PAD4 (hPAD4). Here, we assessed whether anti-hPAD4 status in RA predicted disease outcome after antitumour necrosis factor (anti-TNF)-alpha therapy. METHODS: We analysed RA sera obtained at baseline (n = 40) and after 1 year on anti-TNF-alpha therapy (n = 33) for anti-hPAD4 IgG. Association analyses between baseline anti-hPAD status and disease progression were performed. RESULTS: We found that 17 of 40 patients (42.5%) were serum anti-hPAD4 positive at baseline, and the anti-hPAD4 IgG levels were stable over 1 year on anti-TNF-alpha therapy. At baseline, there were indications that anti-hPAD4 positive patients had more severe disease than the negative patients. After 1 year on anti-TNF-alpha therapy, the anti-hPAD4 positive patients displayed a persistently elevated disease activity score using 28 joint counts score and increased progression in the van der Heijde-modified Sharp erosion score. Accordingly, more anti-hPAD4 positive than negative patients presented an increase in van der Heijde-modified Sharp erosion scores >0 over 1 year. CONCLUSIONS: Anti-hPAD4 IgG can be detected in a subset of RA sera and the levels are stable after initiation of anti-TNF-alpha therapy. Serum anti-hPAD4 may predict persistent disease activity and radiographic progression in patients with RA receiving anti-TNF-alpha therapy.

Hafström I, Albertsson K, Boonen A, van der Heijde D, Landewé R, Svensson B, Anonymous00040. · The Rheumatology Unit, Karolinska Institute, Karolinska University Hospital, Huddinge, Stockholm, Sweden. · Ann Rheum Dis. · Pubmed #18420939 No free full text.

Abstract: OBJECTIVE: To evaluate if remission induced by low-dose prednisolone during the first 2 years of rheumatoid arthritis (RA) in the BARFOT glucocorticoid (GC) study had a sustained effect on radiological damage for a total of 4 years. METHODS: A total of 150 of 211 eligible patients with RA who had been randomised to the 7.5 mg prednisolone group (P) or no prednisolone group (NoP) in addition to the initial disease-modifying antirheumatic drugs were included. Radiographs of hands and feet were scored using the Sharp-van der Heijde scoring method. A patient was considered to be in remission if the 28-joint count disease activity score was <2.6. RESULTS: Mean (SD) age was 53 (14) and 57 (12) years for the patients in the P and NoP groups, respectively. 64% were female, 64% rheumatoid factor positive, and disease duration at baseline was 6 months. At 2 years the proportion of patients in remission in the P and NoP groups was 55 vs 30%, p = 0.003. Longitudinal analysis showed that over the entire course of the disease, patients on prednisolone had a higher probability of being in remission. Patients in remission at 2 years, compared with those not in remission, had significantly lower total Sharp score, erosion score and joint space narrowing score at 2 and 4 years. The changes in bone mineral density during the 4 years did not differ between those in remission and those with active disease, and were similar in the two treatment groups. CONCLUSIONS: Prednisolone 7.5 mg daily in addition to disease-modifying anti-rheumatic drugs increases the rate of remission in patients with early RA, which has a beneficial and sustained effect on radiological damage.

van der Heijde D, Landewé R, Boonen A, Einstein S, Herborn G, Rau R, Wassenberg S, Weissman BN, Winalski CS, Sharp JT. · Department of Rheumatology, Leiden University Medical Center, PO Box 9600, Leiden 2300 RC, The Netherlands. · Arthritis Res Ther. · Pubmed #17605816 links to  free full text

Abstract: The objective of the present study was to test the hypothesis that experts recognize repair of erosions and, if so, to determine which, if any, morphologic features permitted them to recognize the repair. We also tested whether scoring by a standard method detected repair. Seven experienced readers of radiographs in rheumatoid arthritis were presented with 64 sets of single joints-of-interest at two time points, randomized and blinded for the correct sequence. The readers assessed which joint was better, and recorded whether any of six specific features were seen. Two independent readers, experienced in scoring by the van der Heijde-modified Sharp method who were not on the expert panel, then scored the complete films that included the joint-of-interest. The panel agreed very well on which of two joints was better, and, even though they did not know the true sequence, the panel accurately assigned a sequence slightly better than chance alone (58%) but worse than their agreement on which image was 'better or worse' (78%). The readers therefore indirectly assigned repair by choosing the second film as the best. Putative repair features were seen in cases of both repair and progression, and were not discriminatory. Similar results were obtained when the experts were presented with the entire hand or foot containing the joint-of-interest. In the third repair exercise, two independent readers who scored whole hands and feet using a standard method found a mean negative score in 22/60 joints-of-interest. All 22 joints were also scored as repair by the panel. Repair was detected reliably by a majority of the panel on viewing paired images based on a better/worse decision and assigning sequence in a set of images that were blinded for sequence by an independent project manager. In this test set of images, repair was manifested by a reduction in the size of erosion in many cases. Size was one feature that aided the experts to detect repair but cannot be the only one; the experts had to find other features to determine whether a smaller erosion was the first in a sequence of radiographs in a patient with progressive damage or was the second film in a patient exhibiting repair. The change in size of erosion was also picked up by independent readers applying the van der Heijde-modified Sharp scoring method and was reflected in their scores.

Bansback N, Maetzel A, Drummond M, Anis A, Marra C, Conway P, Boers M, Tugwell P, Boonen A. · Centre for Health Evaluation and Outcome Sciences, St. Paul's Hospital, Vancouver, British Columbia, Canada. · J Rheumatol. · Pubmed #17477483 No free full text.

Abstract: Since healthcare resources are scarce, choices have to be made on how they will be allocated. The use of economic evaluations using cost-effectiveness analyses has increased rapidly as policymakers have realized their value in maximizing the population's benefits (in terms of length of life and health status) within a given budget. Following efforts by OMERACT to create reference case definitions for the conduct of economic evaluation in rheumatoid arthritis, osteoporosis, and osteoarthritis, we review various methodological areas and research decisions that could benefit from a consensus between researchers, clinicians, and drug developers in terms of an ankylosing spondylitis (AS) reference case. Ten methodological issues are presented that will be important for future development of evaluations. Tentative proposals to define the issues in a reference case for AS are made, along with recommendations for further research.

Uhlig T, Lillemo S, Moe RH, Stamm T, Cieza A, Boonen A, Mowinckel P, Kvien TK, Stucki G. · National Resource Center for Rehabilitation in Rheumatology, Department of Rheumatology, Diakonhjemmet Hospital, Postboks 23 Vinderen, N-0319 Oslo, Norway. · Ann Rheum Dis. · Pubmed #17223659 No free full text.

Abstract: BACKGROUND: The comprehensive ICF Core Set for rheumatoid arthritis (RA) is a selection of 96 categories from the International Classification of Functioning, Disability and Health (ICF), representing relevant aspects in the functioning of RA patients. OBJECTIVES: To study the reliability of the ICF Core Set for RA in rheumatological practice, and to explore the metric of the qualifiers' scale. METHODS: 25 RA patients from an outpatient department of rheumatology were interviewed using the ICF Core Set for RA (76% females, mean (SD) age 57.5 (12.5) years, disease duration 15.9 (14.6) years). Interviews were performed independently by both a physiotherapist and an occupational therapist on the same day and again after one week by one of them. The severity of the patients' problems was quantified on a qualifier scale ranging from 0 (no problem) to 4 (complete problem). Analyses of intra-rater and inter-rater agreement, kappa statistics, and Rasch analyses were applied. RESULTS: Mean intra-rater (inter-rater) complete agreement for all categories was seen in 59% (47%) of observations, ranging from 29% (0%) to 96% (80%) for individual categories. Weighted kappa statistics with value > or =0.4 showed reliability in 86% of categories within raters, and in 43% of categories between raters. Improved inter-rater and intra-rater reliability was observed with a reduced number of qualifiers for the categories. CONCLUSIONS: Inter-rater and intra-rater reliability of the ICF Core Set of RA was low to moderate. The metric of the qualifiers' scale may be improved by reducing the number of qualifiers to three for all components.

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.

Matricali GA, Boonen A, Verduyckt J, Taelman V, Verschueren P, Sileghem A, Corluy L, Westhovens R. · No affiliation provided · Ann Rheum Dis. · Pubmed #16905588 No free full text.

This publication has no abstract.

van Staa TP, Geusens P, Zhang B, Leufkens HG, Boonen A, Cooper C. · Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #16899499 links to  free full text

Abstract: OBJECTIVES: There are few data on the cost-effectiveness of bisphosphonates with oral glucocorticoids (GCs). An individual patient-based pharmaco-economic model was developed. METHODS: Data were obtained from a cohort of oral GC users aged 40+ (n = 190 000) in the UK General Practice Research Database. Individualized fracture and mortality risks were calculated specific for age, sex, daily and cumulative GC dose, indication and other clinical risk factors. UK costs of medication and direct costs of fracture were obtained from National Institute for Clinical Excellence and used to estimate costs per quality-adjusted life-year (QALY) gained and fracture prevented for bisphosphonates in patients treated for 5 yrs with GCs. RESULTS: With the use of 5 mg GCs daily, the cost per one QALY gained with bisphosphonates was 41k UK pounds (95% confidence intervals 22-72k) in women aged <60 [men 40k pounds (29-54k)], 17k pounds (13-24k) in women aged 60-79 [men 43k pounds (31-60k)], 5k pounds(3-6k) in women aged 80+ [men 35k pounds (25-46k)]. With 15 mg GC, these figures were 17k pounds (14-21k), 13k pounds (10-16k) and 15k pounds (9-26k) in women and 22k pounds (17-26k), 34 pounds (23-53k) and 33k pounds (27-42k) in men, respectively. When stratifying by overall fracture risk and life expectancy at the start of GC therapy, cost per QALY increased with decreasing life expectancy. Patients with rheumatoid arthritis had comparatively better cost-effectiveness, given higher fracture risk and better life expectancy. CONCLUSIONS: The cost-effectiveness of bisphosphonates varied substantially. Bisphosphonates can be considered cost-effective in patients with higher fracture risks, such as elderly patients (with a life expectancy over 5 yrs), and younger patients with a fracture history, low body mass index, rheumatoid arthritis or using high GC doses.

Evers S, Paulus A, Boonen A. · Maastricht University, Faculty of Health Sciences, Department of Health, Organisation, Policy and Economics, PO Box 616, 6200 MD Maastricht, The Netherlands. · Int J Integr Care. · Pubmed #16896408 links to  free full text

Abstract: The main purpose of this practice paper is to describe and analyse the possibilities and complexities of integrated health care across borders. First, we portray an ideal scenario for this type of care with a case of patients suffering from rheumatoid arthritis and living in the Dutch-Belgian frontier area. It shows how cross border care enhances continuity of care/tailor-made care and the other way around. Secondly, based on different literature sources, we describe actual regulations on health care across borders. We show that these regulations can be a major hindrance to integrated care. This raises questions on the scope and content of policies directed at both cross border and integrated care.

Boonen A, Matricali GA, Verduyckt J, Taelman V, Verschueren P, Sileghem A, Corluy L, Westhovens R. · No affiliation provided · Ann Rheum Dis. · Pubmed #16611873 links to  free full text

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Svensson B, Boonen A, Albertsson K, van der Heijde D, Keller C, Hafström I. · University of Lund, Lund, Sweden. · Arthritis Rheum. · Pubmed #16255010 links to  free full text

Abstract: OBJECTIVE: To assess the efficacy of low-dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis (RA). METHODS: At the start of their initial treatment with a disease-modifying antirheumatic drug (DMARD), patients with early (duration < or =1 year) active RA were randomly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years. Radiographs of the hands and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde. Remission was defined as a Disease Activity Score in 28 joints of <2.6. Bone mineral density was measured by dual x-ray absorptiometry at baseline and after 2 years. RESULTS: Of the 250 patients included, 242 completed the study and 225 had radiographs available both at baseline and at 2 years. At 2 years, the median and interquartile range (IQR) change in total Sharp score was lower in the prednisolone group than in the no-prednisolone group (1.8 [IQR 0.5-6.0] versus 3.5 [IQR 0.5-10]; P = 0.019). In the prednisolone group, there were fewer newly eroded joints per patient after 2 years (median 0.5 [IQR 0-2] versus 1.25 [IQR 0-3.25]; P = 0.007). In the prednisolone group, 25.9% of patients had radiographic progression beyond the smallest detectable difference compared with 39.3% of patients in the no-prednisolone group (P = 0.033). At 2 years, 55.5% of patients in the prednisolone group had achieved disease remission, compared with 32.8% of patients in the no-prednisolone group (P = 0.0005). There were few adverse events that led to withdrawal. Bone loss during the 2-year study was similar in the 2 treatment groups. CONCLUSION: Prednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA, provided a high remission rate, and was well tolerated. Therefore, the data support the use of low-dose prednisolone as an adjunct to DMARDs in early active RA.

Westhovens R, Boonen A, Verbruggen L, Durez P, De Clerck L, Malaise M, Mielants H. · Department of Rheumatology, University Hospitals KU Leuven, Belgium. · Clin Rheumatol. · Pubmed #15895197 No free full text.

Abstract: The aim of this study was to compare the socioeconomic consequences of early and late rheumatoid arthritis in Belgium and to assess the patient out-of-pocket contributions. This multicentre longitudinal study in Belgium evaluated patients with rheumatoid arthritis. Early disease was defined as diagnosis since less than 1 year. At baseline sociodemographic and disease characteristics were assessed and during the following year patients recorded all healthcare- and non-healthcare-related direct costs and out-of-pocket contributions. The study included 48 patients with early and 85 patients with late rheumatoid arthritis. Mean disease duration was 0.5 vs 12.5 years in patients with early and late rheumatoid arthritis, respectively. The disease activity score (DAS28) was comparable between both groups (4.1 vs 4.5, p = 0.14), but physical function (Health Assessment Questionnaire, HAQ) was more impaired in patients with long-standing disease (1.0 vs 1.7, p < 0.001). Work disability had increased from 2% in patients with early to 18% in patients with late disease. The annual societal direct costs per patient were 3055 Euros (median: 1518 Euros) opposed to 9946 Euros (median: 4017 Euros) for early and late rheumatoid arthritis, respectively. The higher direct cost for patients with long-standing disease was seen for all categories, but especially for physiotherapy and need for devices and adaptations. Patients with early as well as late disease contribute out of pocket about one-third to the direct healthcare costs. Within each group, HAQ was a strong determinant of costs. In Belgium, patients with long-standing rheumatoid arthritis are nine times more likely to be work disabled than patients with less than 1 year disease duration and have a threefold increase in costs. Differences in healthcare consumption between patients could be mainly explained by differences in physical function (HAQ).

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.

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.

Dadoniene J, Stropuviene S, Venalis A, Boonen A. · Institute of Experimental adn Clinical Medicine, Vilnius University, Vilnius, Lithuania. · Arthritis Rheum. · Pubmed #15188330 links to  free full text

Abstract: OBJECTIVE: To evaluate labor force characteristics among patients with rheumatoid arthritis (RA) in Lithuania. To assess if Lithuania's transition from a state-planned to a free-market economy after 1990 changed the employment perspectives of patients with RA. METHODS: RA patients, age 16-65 years (n = 238), were randomly selected from the RA register in Vilnius. They completed questions about sociodemographics, working status, and disease characteristics, they underwent a clinical examination, and they completed the modified Health Assessment Questionnaire and the Short Form 36. RESULTS: Age- and sex-adjusted employment was 24.2% lower and work disability 51.7% higher in patients compared with the general population in Lithuania. After 10 years of disease, 48% of the patients had withdrawn from the labor force. In those with a paid job, the average sick leave in the past year was 31.9 days compared with the national average of 10.8 days. Although disease activity was not significantly different in employed compared with work-disabled patients, physical function and perceived quality of life (except general health) were worse among patients with work disability. The change in economic organization in 1990 was noted to increase the risk for work withdrawal by a factor of 2.75 (95% confidence interval 1.68-4.53). CONCLUSION: In Lithuania, the impact of RA on work disability is important. Although work disability in Lithuanian patients with RA seems more pronounced compared with reports from Western societies, variables associated with work disability are comparable. The transition to a market-orientated economy in 1990 increased the risk of becoming work disabled.

Chorus AM, Miedema HS, Boonen A, Van Der Linden S. · Division of Public Health, TNO Prevention and Health, Leiden, The Netherlands. · Ann Rheum Dis. · Pubmed #14644855 links to  free full text

Abstract: OBJECTIVE: To investigate the relationship between work and quality of life (QOL) in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) aged 16-59. METHODS: 1056 patients with RA and 658 with AS were included in the study. Data were obtained by postal questionnaire, which included several generic and disease related QOL instruments. Separate dimensions and physical and mental summary scores from the SF-36 were compared. Stepwise multiple regression was performed to study the relationship between work and physical and mental health related QOL, including disease related factors, coping, and fatigue. RESULTS: Physical health related QOL was reported to be worse, and mental health related QOL better, in RA than in AS in people of working age. No differences between RA and AS were found in somatic pain, physical role functioning, social functioning, emotional role functioning, vitality, or general health perception; nor were there any significant differences in fatigue and behavioural coping styles. Work was positively associated with physical health related QOL in both groups and, after disease characteristics, was the most important determinant. No association was found with mental health related QOL. CONCLUSIONS: Although physical health related QOL was worse in patients with RA, the impact on several dimensions of health related QOL in patients with RA and AS of working age under rheumatological care was comparable. Patients with RA and AS experienced similar limitations in physical role functioning, including work. Work is an important independent external determinant of physical health related QOL, but not of mental health related QOL.

Sharp JT, Van Der Heijde D, Boers M, Boonen A, Bruynesteyn K, Emery P, Genant HK, Herborn G, Jurik A, Lassere M, McQueen F, Østergaard M, Peterfy C, Rau R, Strand V, Wassenberg S, Weissman B, Anonymous00464. · University of Washington, Seattle, Washington, USA. · J Rheumatol. · Pubmed #12734916 No free full text.

Abstract: The committee was charged with determining whether healing of erosions in rheumatoid arthritis (RA) occurs. Two exercises were performed: The first asked the committee members, as a panel of experts, to express agreement or disagreement with the presence of improvement and features of bone reaction to injury in images submitted by members as examples of healing. The second presented panel members with 28 pairs of serial images, 14 chosen to illustrate progression and 14 chosen to illustrate repair. Agreement was tested on 8 items: global judgment on which image in the pair was better, relative size of the erosion in the 2 images, judgment on which image was first, presence and extent of sclerosis, cortication, filling-in, remodeling, and reconstituting normal structure. Our results showed good agreement, among the 15 respondents, on global assessment of which image was better and which image showed the smaller erosion. Correct assignment of sequence was only slightly better than expected by chance (in 65% of the cases). Agreement was poor regarding the presence of morphologic features of bone repair. A majority of a panel of experts agreed on which 2nd images in a set of paired, serial images represented improvement and which showed progression based on global assessment of which was better and on size of erosion. Features of bone repair were not distinctive and did not enable the panel to deduce the correct sequence of the serial images. This study provides evidence that repair of bone damage in RA does occur, resulting in some degree of improvement, which was recognized by a majority of a panel of experts.