'Insights in the relationship of joint space narrowing versus erosive joint damage and physical functioning of patients with RA'.

OBJECTIVE: To evaluate the contribution of joint space narrowing (JSN) and erosions in general and in four different joint groups in relation to physical disability in rheumatoid arthritis (RA). METHODS: 5-year follow-up data from the Behandel Strategieën (BeSt) trial were used, where 508 patients with recent onset RA were treated aiming at a disease activity score≤2.4. Joint damage was assessed annually and scored according to the Sharp-van der Heijde method. Physical disability was measured 3-monthly with the Health Assessment Questionnaire (HAQ). Generalised Estimating Equations analyses were performed to assess the relationship between the HAQ and JSN scores and erosions scores, separately and in joint groups. RESULTS: Overall, damage scores were low, and neither total JSN nor erosions showed a significant effect on HAQ (ß=0.001 95% CI -0.003 to 0.004 and ß=0.002 95% CI -0.001 to 0.006, respectively). Of the total damage scores per joint group, damage in the wrist shows a trend for association with physical disability displaying the largest effect size (ß=0.005 95% CI 0.000 to 0.011). Also in the analysis with erosions per joint group, the wrist was most strongly related with physical functioning (ß=0.016 95% CI 0.003 to 0.029); in the analysis with JSN per joint group no joint group was significantly related to the HAQ. Analysis of all erosion and narrowing scores per joint group in one model reveals only erosions in the wrist to be independently associated with impaired physical functioning (ß=0.017 95% CI 0.003 to 0.030). CONCLUSIONS: Joint damage in the wrist, erosions more than JSN, is associated with impaired physical functioning even in patients with early RA with limited overall damage after 5 years tightly controlled treatment.

A matrix risk model for the prediction of rapid radiographic progression in patients with rheumatoid arthritis receiving different dynamic treatment strategies: post hoc analyses from the BeSt study.

OBJECTIVES: To develop a matrix model for the prediction of rapid radiographic progression (RRP) in subpopulations of patients with recent-onset rheumatoid arthritis (RA) receiving different dynamic treatment strategies. METHODS: Data from 465 patients with recent-onset RA randomised to receive initial monotherapy or combination therapy were used. Predictors for RRP (increase in Sharp-van der Heijde score > or =5 after 1 year) were identified by multivariate logistic regression analysis. For subpopulations, the estimated risk of RRP per treatment group and the number needed to treat (NNT) were visualised in a matrix. RESULTS: The presence of autoantibodies, baseline C-reactive protein (CRP) level, erosion score and treatment group were significant independent predictors of RRP in the matrix. Combination therapy was associated with a markedly reduced risk of RRP. The positive and negative predictive values of the matrix were 62% and 91%, respectively. The NNT with initial combination therapy to prevent one patient from RRP with monotherapy was in the range 2-3, 3-7 and 7-25 for patients with a high, intermediate and low predicted risk, respectively. CONCLUSION: The matrix model visualises the risk of RRP for subpopulations of patients with recent-onset RA if treated dynamically with initial monotherapy or combination therapy. Rheumatologists might use the matrix for weighing their initial treatment choice.

Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis.

OBJECTIVES: To compare the occurrence of drug-free remission, functional ability and radiological damage after 4 years of response-driven treatment according to four different treatment strategies for rheumatoid arthritis (RA). METHODS: Patients with recent-onset, active RA (n = 508) were randomly assigned to four different treatment strategies: (1) sequential monotherapy; (2) step-up combination therapy; (3) initial combination therapy with prednisone and (4) initial combination therapy with infliximab. Treatment was adjusted based on 3-monthly disease activity score (DAS) assessments, aiming at a DAS < or =2.4. From the third year, patients with a sustained DAS <1.6 discontinued treatment. RESULTS: In total, 43% of patients were in remission (DAS <1.6) at 4 years and 13% were in drug-free remission: 14%, 12%, 8% and 18% of patients in groups 1-4, respectively. The absence of anti-cyclic citrullinated peptide antibodies, male gender and short symptom duration were independently associated with drug-free remission. Functional ability and remission were maintained in all four groups with the continuation of DAS-driven treatment, without significant differences between the groups. Significant progression of joint damage was observed in 38% and 31% of patients in groups 3 and 4 versus 51% and 54% of patients in groups 1 and 2 (p<0.05, group 4 versus groups 1 and 2, group 3 versus group 2). CONCLUSIONS: In patients with recent-onset active RA, drug-free remission was achieved in up to 18% of patients. DAS-driven treatment maintained clinical and functional improvement, independent of the treatment strategy. Joint damage progression remained significantly lower after initial combination therapy compared with initial monotherapy.

Value of serum cartilage oligomeric matrix protein as a prognostic marker of large-joint damage in rheumatoid arthritis--data from the RAPIT study.

OBJECTIVE: To investigate the utility of serum COMP level measurements as a predictor of future damage of the weight-bearing (large) joints in RA patients participating in intensive exercise. METHODS: Data of the 281 completers of a 2-yr randomized controlled trial (Rheumatoid Arthritis Patients In Training; RAPIT) comparing the effects of usual care physical therapy with high-intensity weight-bearing exercises were analysed. The primary outcome variable was defined as the change in radiological joint damage (Larsen score) of the large joints. Potential predictors of outcome were defined: baseline and change in serum level of COMP after 3 months, baseline radiological damage of the large and small joints, number of months on glucocorticoids, change in disease activity and in physical capacity (aerobic fitness and muscle strength) after 2 yrs, and participation in the exercise group. RESULTS: In cross-sectional evaluation of baseline data, we found strong association between the high serum COMP level and current damage of the large joints. Serum COMP level at baseline, however, was not associated with an increased rate of radiological joint damage after 2 yrs of follow-up. Furthermore, neither interaction between baseline COMP level and participation in exercises, nor change in COMP level after 3 months of exercising were associated with future damage of the large joints. CONCLUSION: Neither baseline serum COMP level nor its individual change after 3 months from start of intensive exercise predict longitudinal progression of damage of the large joints in this population.

RAGE activation induces invasiveness of RA fibroblast-like synoviocytes in vitro.

Ligands for the receptor for advanced glycation endproducts (RAGE) are increased in RA synovial fluid (SF), serum and synovium. Since RAGE is present on fibroblast-like synoviocytes (FLS), the present study investigates whether the RAGE ligands HMGB-1 and AGEs are able to stimulate the characteristic, pathological invasive behaviour of these cells. FLS were obtained during joint replacement surgery. FLS were seeded in serum free medium with HMGB-1 or glycated albumin (BSA-AGE) on transwell filters coated with Matrigel. The lower compartment contained medium with serum as a chemoattractant. After three days, the percentage of invading cells was determined and compared to the control invasion. Stimulation with HMGB-1 increased invasiveness to 125% compared to the control (p = 0.001). Addition of anti-RAGE antibody reduced this back to baseline (98%, p = 0.002). Stimulation with BSA-AGE, another RAGE ligand, increased invasiveness to 150% compared to the control (p = 0.003). Addition of anti RAGE was again able to reduce the increased invasiveness back to baseline (95%, p = 0.008). HMGB-1 and BSA-AGE stimulated the invasiveness of RA-FLS by activation of RAGE. As such, RAGE may be an interesting target for therapy directed at the inhibition of synoviocyte activation.

Fibroblast-like synoviocyte-chondrocyte interaction in cartilage degradation.

OBJECTIVE: In vitro models for joint diseases often focus on a single cell type, such as chondrocytes in osteoarthritis (OA) or fibroblast-like synoviocytes (synoviocytes) in rheumatoid arthritis (RA). However, these joint diseases affect the whole joint and interaction between chondrocytes and synoviocytes may play an important role in disease pathology. The current study was designed to study the use of the alginate recovered chondrocyte method as a model for cartilage degradation and to study interaction between chondrocytes and synoviocytes. METHODS: Bovine chondrocytes were cultured in alginate beads for 1 week, subsequently chondrons were retrieved and seeded into transwells. Every two days cartilage-slices were analysed for proteoglycan content (colorimetric, Blyscan GAG kit), collagen content (HPLC) and collagen HP and LP crosslinking (HPLC). For degradation experiments, monocultures of cartilage-slices labelled with (35)S and cocultures with synoviocytes were stimulated with IL-1beta or TNF-alpha. After 7 days, (35)S release was measured taken as a measure of cartilage degradation. RESULTS: After biochemical analysis, three week old cartilage-like slices were chosen to perform cartilage-degradation experiments. Synoviocytes were able to induce cartilage degradation only in the presence of living chondrocytes. In addition, the cytokines interleukin 1 (IL-1beta) and tumor necrosis factor (TNF-alpha) were only able to induce cartilage degradation by chondrocytes, not by synoviocytes. CONCLUSION: These data indicate that the alginate recovered chondrocyte method provides a novel model for cartilage degradation in which the interaction between synoviocytes and chondrocytes can be studied.

Evaluating Adherence to a Treat-to-Target Protocol in Recent-Onset Rheumatoid Arthritis: Reasons for Compliance and Hesitation.

OBJECTIVE: To evaluate rheumatologists' adherence to a low Disease Activity Score (DAS)-steered treat-to-target (T2T) strategy in treatment of patients with rheumatoid arthritis (RA) and to assess associated conditions. METHODS: Data of the BeSt study were used, a multicenter T2T strategy trial with 10-year followup. During 3 monthly visits, the physician answered questions about satisfaction with level of RA suppression, agreement with the study protocol, and agreement with the DAS. Associations between the answers and nonadherence were evaluated. RESULTS: Protocol adherence decreased over time from 100% to 60% per visit, with an average over time of 79%. Rheumatologists mostly agreed with the DAS (80-90% of visits over time) and were satisfied with the treatment steps (75-90%) and with the level of RA suppression (85-90%). The odds for protocol violation were higher when the rheumatologist disagreed with the DAS (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 2.0-2.7 when they thought the DAS overestimated actual disease activity; OR 2.5, 95% CI 2.0-3.1 when they thought the DAS underestimated actual disease activity) or with the next required treatment step (OR 3.0, 95% CI 2.5-3.5), and when the physician was dissatisfied with disease suppression (OR 1.3, 95% CI 1.1-1.6). CONCLUSION: Rheumatologists generally agreed with and followed a 10-year followup DAS-steered T2T strategy. Disagreement with the DAS or the required treatment and dissatisfaction with the level of disease suppression were risk factors for nonadherence. These results indicate the feasibility of continued protocol-driven T2T therapy. For daily practice, adherence to T2T therapy might be improved by adopting the structure components of a clinical trial.

Can we prevent rapid radiological progression in patients with early rheumatoid arthritis?

The aim of this study is to test the performance of a matrix model to predict rapid radiological progression (RRP) in a study population of early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) patients. A matrix model using baseline CRP, erosion score, autoantibody status, and initial treatment choice to predict RRP (increase ≥5 points in Sharp-van der Heijde score (SHS) in 1 year) was derived from the BeSt study where patients with active RA (1987-criteria) were treated with initial monotherapy or combination therapy, aiming at low disease activity. In the IMPROVED study, patients with early RA (2010 criteria) and UA were initially treated with methotrexate and prednisone aiming at remission. A receiver operating characteristics (ROC) curve was used to assess the discriminative value of the model to predict damage progression in the IMPROVED population. Four hundred thirty-one out of 479 patients with RA and 106/122 with UA could be categorized as high, intermediate, low, or very low risk for RRP. One patient, with a very low risk profile, showed RRP. Thirty-two other patients (5 %) showed radiological progression ≥0.5 point SHS; none had a high risk profile and 22 had a very low risk profile. The area under the curve (AUC) of the ROC curve was 0.56 (95% CI 0.45; 0.68). A matrix model predicting RRP based on risk factors identified in recent onset active RA according to the 1987-criteria performed poorly in recent onset RA (2010 criteria) and UA. It appears that known risk factors for damage progression lose their impact with early remission steered treatment, so that RRP might be considered a phenomenon of the past.

Highly increased levels of active stromelysin in rheumatoid synovial fluid determined by a selective fluorogenic assay.

Stromelysin-1 (MMP-3) is an important member of the matrix metalloproteinase family. In joint-degrading diseases like arthritis, elevated levels of MMP-3 protein are detected in synovial fluid using immunological methods. However, these methods do not discriminate between active and inactive enzyme. In the present study, a specific stromelysin activity assay was developed using the selective fluorogenic substrate TNO003 (Dabcyl-Gaba-Arg-Pro-Lys-Pro-Val-Glu / Nva-Trp-Arg-Glu-(EDANS)-Ala-Lys-NH2, / =cleavage site). For its use in biological media, cleavage of TNO003 by enzymes other than stromelysin was effectively blocked by a proteinase inhibitor cocktail. Spiking of MMP-3 to synovial fluid resulted in an MMP-3 concentration-dependent linear increase in activity. The measured MMP-3 activity was not affected by the addition of MMP-13, even in a 5-fold excess over MMP-3. Synovial fluid from rheumatoid arthritis patients demonstrated 100-fold higher levels of active stromelysin than control synovial fluids.

Convenient fluorometric assay for matrix metalloproteinase activity and its application in biological media.

Matrix metalloproteinases (MMPs) are involved in physiological tissue remodeling and pathological conditions like tumour metastasis and joint destruction. Until now, no convenient and sensitive MMP-activity assay in crude media like synovial fluid has been available. Therefore, the highly soluble fluorogenic substrate TNO211 (Dabcyl-Gaba-Pro-Gln-Gly-Leu-Glu(EDANS)-Ala-Lys-NH2), containing the MMP cleavable Gly-Leu bond and EDANS/Dabcyl as fluorophore/quencer combination, was synthesized and characterized as an MMP specific substrate. We show that the fluorogenic assay using TNO211 is sensitive and can detect MMP activity in culture medium from endothelial cells and untreated synovial fluid (SF) from RA and OA patients, and control subjects. MMP activity in SF significantly increased in the order C < OA < RA, thus the frequent use of OA samples as control in studies on RA is debatable.

Fluorogenic MMP activity assay for plasma including MMPs complexed to alpha 2-macroglobulin.

Elevated MMP activities are implicated in tissue degradation in, e.g., arthritis and cancer. The present study was designed to measure MMP enzyme activity in plasma. Free active MMP is unlikely to be present in plasma: upon entering the circulation, active MMP is expected to be captured by the proteinase inhibitor alpha 2-macroglobulin (alpha 2M). Reconstituted MMP-13/alpha 2M complex was unable to degrade collagen (MW 300,000) in contrast to the low-molecular-weight fluorogenic substrate (MW < 1500). Limited access of high-MW substrates to the active site of MMPs captured by alpha 2M presents the most likely explanation. Consistently, the high-MW inhibitor TIMP (MW approximately 28,000) was unable to inhibit MMP/alpha 2M enzyme activity, whereas the low-MW inhibitor BB94 (MW approximately 500) effectively suppressed enzyme activity. By using fluorogenic substrates with Dabcyl/Fluorescein as quencher/fluorophore combin-ation, sensitive MMP-activity assays in plasma were achieved. Spiking of active MMP-13 and MMP-13/alpha 2M complex, and inhibitor studies with TIMP-1 and BB94, indicated that active MMPs are efficiently captured by alpha 2M in plasma. MMP activity was even detected in control plasma, and was significantly increased in plasma from rheumatoid arthritis patients.

No therapeutic effect of plasmin antagonist tranexamic acid in rheumatoid arthritis. A double-blind placebo-controlled pilot study.

OBJECTIVE: In the present study, the effects of plasmin antagonist tranexamic acid (TEA) on urinary pyridinoline excretion rates were investigated in rheumatoid arthritis (RA) patients. METHODS: The study was set up as a double-blind placebo-controlled pilot study. Ten patients received tranexamic acid and 9 received placebo for 12 weeks. Urinary excretion rates of hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) were used as molecular markers of articular cartilage and bone degradation. In addition, clinical parameters of disease activity were assessed and CRP levels were measured. RESULTS: Treatment with TEA did not reduce pyridinoline excretion, nor was any effect observed on clinical parameters of disease activity or on CRP levels. CONCLUSION: The results of the present pilot study show no beneficial effect of TEA as adjuvant therapy in RA patients with respect to joint destruction or disease activity.

Amyloidosis mimicking rheumatoid arthritis.

A 49-year-old man presented a clinical picture suggesting seronegative rheumatoid arthritis. He developed severe joint contractions, pasty synovial swelling, macroglossia and proteinurie. Subsequent investigations disclosed light-chain multiple myeloma and A1-amyloid deposits in synovial tissue and skin. A1-amyloidosis should be considered in the differential diagnosis of patients with seronegative polyarthritis. Clues to the diagnosis of amyloid arthropathy are a carpal tunnel syndrome, early occurrence of joint contractures in combination with a relatively mild synovitis and a low ESR as well as the presence of other possible organ involvement with amyloidosis.

Rheumatic manifestations of hepatitis C virus infection.

Infection with hepatitis C virus (HCV) is a major cause of chronic hepatitis and has been associated with the occurrence of mixed cryoglobulinaemia. Treatment with interferon alpha can lower the titres of HCV, improve liver lesions and decrease cryoglobulins. In this report, a patient with HCV infection is described who developed arthritis, cutaneous vasculitis and sialoadenitis, together with hepatitis and cryoglobulinaemia. Clinical remission, particularly of the systemic symptoms, was achieved during treatment with interferon alpha.

The relationship between disease activity and depressive symptoms severity and optimism--results from the IMPROVED study.

To assess depressive symptoms severity and dispositional optimism in patients with recent onset arthritis both before and after 4 months treatment. Two hundred twenty-two patients with recent onset RA and undifferentiated arthritis in the IMPROVED study filled out the Beck Depression Inventory (BDI-II) to assess depressive symptoms severity and the Life Orientation Test Revised (LOT-R) to measure optimism before and after 4 months of treatment. All patients were treated with methotrexate 25 mg/week and prednisone 60 mg/day (tapered to 7.5 mg/day in 7 weeks). Linear regression analysis was used to assess the association between the disease activity score (DAS) and its components (tender joint count, general well-being measured with a visual analogue scale (VAS), swollen joint count, and erythrocyte sedimentation rate) with the BDI-II an LOT-R scores. In general, depressive symptoms were mild. The DAS was an independent predictor of depressive symptoms scores both at baseline and after 4 months follow-up, in particular tender joint count and VAS global health. Disease activity was not associated with the level of optimism. Nevertheless, patients who achieved clinical remission improved significantly more in both depression score and optimism score than patients who did not. Patients with early arthritis report improvement in depressive symptoms and optimism with improvement in disease activity and achieving clinical remission. Depression scores are associated with pain and unwell being but not with swollen joint counts and inflammatory parameters.

Changes in hand bone mineral density and the association with the level of disease activity in patients with rheumatoid arthritis: bone mineral density measurements in a multicenter randomized clinical trial.

OBJECTIVE: To determine if metacarpal bone mineral density (mBMD) gain occurs in patients with rheumatoid arthritis (RA). If mBMD loss is driven by inflammation, we expect to find mBMD gain in patients who are in remission. METHODS: mBMD was measured by digital x-ray radiogrammetry in consecutive radiographs of 145 patients with RA with either continuous high disease activity (HDA; Disease Activity Score [DAS] >2.4), low disease activity (LDA; 1.6 ≥ DAS ≤ 2.4), or continuous clinical remission (CR; DAS <1.6) during a 1-year observation period. The association of mBMD changes with disease activity was investigated with multinomial regression analysis. Next, clinical variables associated with mBMD gain were identified. RESULTS: Mean change in mBMD in CR patients was -0.03%, compared to -3.13% and -2.03% in HDA and LDA patients, respectively (overall, P < 0.001). Of the patients in CR, 32% had mBMD loss (less than or equal to -4.6 mg/cm2/year), compared to 62% and 66% of the patients with HDA or LDA, respectively, whereas 26% of the patients in CR had mBMD gain (≥4.6 mg/cm2/year), compared to 2% of the patients with HDA and 5% of the patients with LDA. Patients in CR had a higher chance of having mBMD gain, compared with LDA and HDA (relative risk [RR] 14.9, 95% confidence interval [95% CI] 3.0-18.7 and RR 4.7, 95% CI 1.2-6.3, respectively). CR, hormone replacement therapy, and lower age were significant independent predictors of mBMD gain. CONCLUSION: In RA, mBMD gain occurs primarily in patients in continuous (≥1 year) CR and rarely in patients with continuous HDA or LDA. This suggests that mBMD loss is driven by inflammation.

Motivation as a determinant of physical activity in patients with rheumatoid arthritis.

OBJECTIVE: A sufficient level of physical activity is important in reducing the impact of disease in rheumatoid arthritis (RA) patients. According to self-determination theory, the achievement and maintenance of physical activity is related to goal setting and ownership, which can be supported by health professionals. Our objective was to examine the association between physical activity and the extent to which RA patients 1) believe that physical activity is a goal set by themselves (autonomous regulation) or by others (coerced regulation) and 2) feel supported by rheumatologists (autonomy supportiveness). METHOD: A random selection of 643 RA patients from the outpatient clinics of 3 hospitals were sent a postal survey to assess current physical activity level (Short Questionnaire to Assess Health-Enhancing Physical Activity), regulation style (Treatment Self-Regulation Questionnaire), and the autonomy supportiveness of their rheumatologists (modified Health Care Climate Questionnaire). RESULTS: Of the 271 patients (42%) who returned the questionnaire, 178 (66%) were female, their mean +/- SD age was 62 +/- 14 years, and their mean +/- SD disease duration was 10 +/- 8 years. Younger age, female sex, higher education level, shorter disease duration, lower disease activity, and a more autonomous regulation were univariately associated with more physical activity. Hierarchical multiple regression analyses demonstrated that younger age and a more autonomous regulation were significantly associated with a higher physical activity level (P = 0.000 and 0.050, respectively). CONCLUSION: Regulation style was a significant determinant of physical activity in RA patients. This finding may contribute to further development of interventions to enhance physical activity in RA patients.

Exploring the public health impact of an intensive exercise program for patients with rheumatoid arthritis: a dissemination and implementation study.

OBJECTIVE: To evaluate the implementation of an intensive group exercise program in patients with rheumatoid arthritis (RA). METHODS: In 4 regions in The Netherlands, the Rheumatoid Arthritis Patients In Training exercise program was implemented on a limited scale. Evaluation using the RE-AIM model included: Reach, the proportion of the target population participating; Efficacy, effects on muscle strength, aerobic capacity, functional ability, and psychological functioning; Adoption, program adoption by stakeholders; Implementation, intervention quality (quality audits); and Maintenance, stakeholders' willingness to continue the program in the future. RESULTS: Twenty-five physical therapists from 14 practices were trained to provide the program. In total, 150 RA patients were recruited (by estimation, 2% of the target population). Of the 81 patients who had finished the 12-month intervention and were available for followup directly after the intervention, 62 patients provided clinical data. Muscle strength improved significantly, whereas aerobic capacity, functional ability, psychological functioning, and disease activity did not change. All 9 informed local patient organizations facilitated patient recruitment, and 35 of 51 rheumatologists involved referred one or more patients. All 10 approached health insurance companies funded the program for 12 months. The quality audits showed sufficient quality in 9 of 12 practices. All of the providers of the program were willing to provide the program in the future, whereas future reimbursement by health insurance companies remained unclear. CONCLUSION: The implementation of an intensive exercise program for RA patients on a limited scale can be considered successful regarding its reach, adoption, and implementation. The limited effectiveness and the limited data regarding maintenance warrant additional research.

Assistive devices: usage in patients with rheumatoid arthritis.

We describe the usage of various assistive devices and identify factors associated with usage in patients with rheumatoid arthritis (RA). A cross-sectional, multicentre study was performed in three outpatient rheumatology clinics in the Netherlands. Two hundred forty patients with RA participated in the study. The main measures were questionnaires and a semi-structured interview regarding the possession and usage of 21 common assistive devices in the ISO9999 categories orthopaedic footwear, personal care, mobility, household and adaptations for housing. Potential factors associated with usage included sociodemographic variables, health status, quality of life, coping strategies, self-efficacy, outcome expectations and satisfaction. Out of 240 patients, 213 (89%) had one or more assistive devices in possession (median number of devices 3.0, interquartile range 3.0). The proportions of patients never using a device in possession varied between 8% for orthopaedic insoles and 23% for grab bars. The main factors related to usage varied among categories, but common determinants were a specific impairment or disability, satisfaction with the device or related services, self-efficacy and the number of devices in possession. In conclusion, in patients with RA, possession rates are high, with 23% or less of the devices in possession being abandoned. Overall, satisfaction rates were high. Factors associated with usage varied among categories and comprised, apart from the number of devices in possession and variables related to health status, also aspects of satisfaction with the device or related services or self-efficacy. The latter findings underline the need for a systematic evaluation of the outcomes of assistive devices by prescribing health professionals or suppliers in every individual case.

Progression of joint damage in early rheumatoid arthritis: association with HLA-DRB1, rheumatoid factor, and anti-citrullinated protein antibodies in relation to different treatment strategies.

OBJECTIVE: To determine the association of HLA-DRB1, rheumatoid factor (RF), and anti-citrullinated protein antibody (ACPA) status with progression of joint damage in early rheumatoid arthritis (RA) treated according to different treatment strategies. METHODS: The present study was conducted using data from the BeSt study (Behandelstrategieën voor Reumatoide Artritis [treatment strategies for rheumatoid arthritis]), a randomized trial comparing 4 targeted (toward achievement of a Disease Activity Score [DAS] of < or =2.4) treatment strategies: sequential monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with methotrexate, sulfasalazine, and prednisone (group 3), and initial combination therapy with methotrexate and infliximab (group 4), in 508 patients with early RA. Multivariate logistic regression analysis was used to predict progressive disease (increase of Sharp/van der Heijde score over 2 years beyond the smallest detectable change [4.6]) according to the presence or absence of the shared epitope (SE), DERAA, RF, and ACPA, with correction for other baseline characteristics. RESULTS: Progressive disease could not be predicted by presence of the SE: the odds ratio in groups 1, 2, 3, and 4, respectively, was 1.4, 2.6, 1.9, and 3.0. DERAA carriership did not protect against progressive disease (odds ratio 0.4, 1.4, 0.9, and 0.9 in groups 1, 2, 3, and 4, respectively). RF positivity and ACPA positivity predicted progressive disease in group 1 (odds ratio 4.7 [95% confidence interval 1.5-14.5] for RF and 12.6 [95% confidence interval 3.0-51.9] for ACPA), but not in groups 2-4 (for RF, odds ratio [95% confidence interval] 1.5 [0.5-4.9], 1.0 [0.3-3.3], and 1.4 [0.4-4.8] in group 2, group 3, and group 4, respectively; for ACPA, odds ratio [95% confidence interval] 3.4 [0.8-14.2], 1.7 [0.5-5.4], and 1.8 [0.5-6.8] in group 2, group 3, and group 4). CONCLUSION: In patients with early RA treated with the goal of tight control of the DAS, no significant association between HLA-DRB1 status and radiographic progression was found. RF and ACPA were predictive of progressive disease only in patients treated with sequential monotherapy. These observations suggest that effective treatment can prevent radiographic progression, even in patients with risk factors for severe damage.