Treatment strategies in recent-onset rheumatoid arthritis : the best study

This thesis describes the outcomes of 2 year follow-up of the BeSt study (Behandel-Strategieen). This is a multicenter, randomized clinical trial comparing 4 different treatment strategies in patients with recent-onset active rheumatoid arthritis: 1. sequential monotherapy, starting with methotrexate, switching to another antirheumatic drug in case of an insufficient response; 2. step-up combination therapy, also starting with methotrexate, adding other antirheumatic drugs in case of an insufficient response; 3. initial combination therapy with methotrexate, sulphasalazine and high-dose tapered prednisone; 4. initial combination therapy with methotrexate and infliximab. In all groups the goal was to achieve a disease activity score (DAS) __2.4 (low disease activity). The DAS was measured 3-monthly by a research nurse, blinded for the allocated group. The physician then adjusted therapy according to the protocol. During the 2 year follow-up, groups 3 and 4 had a more rapid clinical response, less joint damage and less treatment adjustments than groups 1 and 2. Interestingly, groups 1 and 2 did better than expected. This is probably the result of aimimg for low disease activity. Most patients prefer treatment with the newest drug. The higher costs of infliximab can largely be compensated by savings on productivity.UBL - phd migration 201

Changes in hand and generalised bone mineral density in patients with recent-onset rheumatoid arthritis

Objectives: To evaluate changes in bone mineral density (BMD) in the hands, hip and spine after 1 and 2 years of follow-up, in relation to antirheumatic and antiresorptive therapies and disease and demographic variables in patients with recent-onset rheumatoid arthritis ( RA). Methods: Changes in BMD measured in metacarpals 2-4 by digital x-ray radiogrammetry and in the hip and spine by dual energy x-ray absorptiometry were assessed at baseline and after 1 and 2 years of follow-up in 218 patients with recent-onset RA from the BeSt study, who received one of four treatment strategies: sequential monotherapy ( group 1); step-up combination therapy ( group 2); initial combination therapy with tapered high-dose prednisone ( group 3); or initial combination therapy with infliximab (group 4). Results: After 1 and 2 years, there was significant BMD loss in all locations, with significantly greater BMD loss in the hands than generalised BMD loss in the hip and spine. Initial combination therapy with prednisone or infliximab were associated with less hand BMD loss compared with initial monotherapy after 1 and 2 years (-0.9 and -1.6%, -0.6 and -1.4%, -1.7 and -3.3%, and -2.6 and -3.6% for group 4-1 after 1 and 2 years, overall p = 0.001 and p = 0.014, respectively). Progression in erosions was independently associated with increased BMD loss both in the hands and hip after 1 year. The use of bisphosphonates protected only against generalised BMD loss in the hip and spine. Conclusions: The association between joint damage progression and both hand and generalised BMD loss in RA suggests common pathways between these processes, with hand BMD loss occurring earlier in the disease course than generalised BMD los

The perspective of people with axial spondyloarthritis regarding physiotherapy : room for the implementation of a more active approach

Objectives. Physiotherapy is recommended in the management of people with axial spondyloarthritis (axSpA), with new insights into its preferred content and dosage evolving. The aim of this study was to describe the use and preferences regarding individual and group physiotherapy among people with axSpA. Methods. A cross-sectional survey was conducted among people with axSpA living in The Netherlands (NL) and Switzerland (CH). Results. Seven hundred and thirteen people with axSpA participated (56.7% male, median age 55 years, median Assessment of Spondyloarthritis International Society Health Index score 4.2). Response rates were 45% (n¼206) in NL and 29% in CH (n¼507). Of these participants, 83.3% were using or had been using physiotherapy. Individual therapy only was used or had been used by 36.7%, a combination of individual plus land- and water-based group therapy by 29.1% and group therapy by only 5.3%. Fewer than half of the participants attending individual therapy reported active therapy (such as aerobic, muscle strength and flexibility exercises). Although the majority (75.9%) were not aware of the increased cardiovascular risk, participants showed an interest in cardiovascular training, either individually or in a supervised setting. If supervised, a majority, in CH (75.0%) more than in NL (55.7%), preferred supervision by a specialized physiotherapist. Conclusion. The majority of people with axSpA use or have used physiotherapy, more often in an individual setting than in a group setting. The content of individual therapy should be more active; in both therapy settings, aerobic exercises should be promoted. In particular, enabling people with axSpA to perform exercises independently would meet their needs and might enhance their daily physical activity

Being as Normal as Possible: How Young People Ages 16–25 Years Evaluate the Risks and Benefits of Treatment for Inflammatory Arthritis

Objective To explore how young people (ages 16–25 years) with inflammatory arthritis evaluate the risks and benefits of treatment, particularly treatment with biologic therapies. Methods This qualitative study involved in-depth interviews (n = 44) with young people, trusted others (e.g., parents), and health professionals; audio-recordings (n = 4) of biologic therapy–related consultations; and focus groups (n = 4). Analysis used techniques from grounded theory (open and focused coding, constant comparison, memoing, and mapping). Results Young people aspired to live what they perceived as a “normal” life. They saw treatment as presenting both an opportunity for and a threat to achieving this. Treatment changes were therefore subject to complex and ongoing evaluation, covering administration, associated restrictions, anticipated effects, and side effects. Information sources included expert opinion (of professionals and other patients) and personal experience. Previous treatments provided important reference points. Faced with uncertain outcomes, young people made provisional decisions. Both trusted others and health professionals expressed concern that young people were too focused on short-term outcomes. Conclusion Young people value treatment that helps them to live a “normal” life. There is more to this than controlling disease. The emotional, social, and vocational consequences of treatment can be profound and lasting: opportunities to discuss the effects of treatment should be provided early and regularly. While making every effort to ensure understanding of the long-term clinical consequences of taking or not taking medication, the wider impact of treatment should not be dismissed. Only through understanding young people's values, preferences, and concerns can a sustainable balance between disease control and treatment burden be achieved

Health-related quality of life and functional ability in patients with early arthritis during remission steered treatment: results of the IMPROVED study

INTRODUCTION: The aim of this study was to investigate patient reported outcomes (PROs) of functional ability and health related quality of life (HRQoL) in patients with early (rheumatoid) arthritis during one year of remission steered treatment. METHODS: In this study, 610 patients with early rheumatoid arthritis (RA) or undifferentiated arthritis (UA) were treated with methotrexate (MTX) and tapered high dose of prednisone. Patients in early remission (Disease Activity Score (DAS) <1.6 after 4 months) tapered prednisone to zero and when in persistent remission, also tapered MTX. Patients not in early remission were randomized to either MTX + hydroxychloroquine + sulphasalazine + prednisone (arm 1) or to MTX + adalimumab (arm 2). Every 4 months, patients filled out the Health Assessment Questionnaire (HAQ) and the McMaster Toronto Arthritis Patient Preference Questionnaire (MACTAR), the Short Form 36 (SF-36) and visual analogue scales (VAS). Change scores were compared between treatment groups. The association with achieving remission was analyzed using linear mixed models. RESULTS: During year 1, patients who achieved early remission had the most improvement in PROs with scores comparable to the general population. Patients in the randomization arms showed less improvement. Scores were comparable between the arms. There was a significant association between achieving remission and scores of HAQ, MACTAR and physical HRQoL. CONCLUSIONS: In early arthritis, PROs of functional ability and HRQoL after one year of remission steered treatment reach normal values in patients who achieved early remission. In patients not in early remission, who were randomized to two strategy arms, PROs improved less, with similar scores in both treatment arms. TRIAL REGISTRATIONS: ISRCTN11916566 and EudraCT2006-006186-1

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

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 monotherap

Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis

Introduction: To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years. Methods: In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years. Results: 68% of the patients had accelerated hand BMD loss (>-0.003 g/cm(2)) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage. Conclusions: In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.Pathophysiology and treatment of rheumatic disease

Interpretation of DAS28 and its components in the assessment of inflammatory and non-inflammatory aspects of rheumatoid arthritis

Background: DAS28 is interpreted as the inflammatory disease activity of RA. Non-inflammatory pain mechanisms can confound assessment. We aimed to examine the use of DAS28 components or DAS28-derived measures that have been published as indices of non-inflammatory pain mechanisms, to inform interpretation of disease activity. Methods: Data were used from multiple observational epidemiology studies of people with RA. Statistical characteristics of DAS28 components and derived indices were assessed using baseline and follow up data from British Society for Rheumatology Biologics Registry participants [1] commencing anti-TNF therapy (n = 10813), or [2] changing between non-biologic DMARDs (n=2992), [3] Early Rheumatoid Arthritis Network participants (n=813), and [4] participants in a cross-sectional study exploring fibromyalgia and pain thresholds (n=45). Repeatability was tested in 34 patients with active RA. Derived indices were the proportion of DAS28 attributable to patient-reported components (DAS28-P), tender-swollen difference and tender:swollen ratio. Pressure pain detection threshold (PPT) was used as an index of pain sensitisation. Results: DAS28, tender joint count, visual analogue scale, DAS28-P, tender-swollen difference and tender:swollen ratio were more strongly associated with pain, PPT and fibromyalgia status than were swollen joint count or erythrocyte sedimentation rate. DAS28-P, tender-swollen difference and tender:swollen ratio better predicted pain over 1 year than did DAS28 or its individual components. Conclusions: DAS28 is strongly associated both with inflammation and with patient-reported outcomes. DAS28-derived indices such as tender-swollen difference are associated with non-inflammatory pain mechanisms, can predict future pain and should inform how DAS28 is interpreted as an index of inflammatory disease activity in RA

Changes in disease characteristics and response rates among patients in the United Kingdom starting anti-tumour necrosis factor therapy for rheumatoid arthritis between 2001 and 2008

Objectives. Anti-TNF therapy has significantly improved outcomes for patients with severe RA. In the UK, changing financial restrictions and increasing experience with their use may have resulted in changes to the way physicians use anti-TNF therapies. The aim of this analysis was to examine changes in disease characteristics and response rates among patients starting anti-TNF therapy for RA over an 8-year period

Prevalence of vertebral fractures in a disease activity steered cohort of patients with early active rheumatoid arthritis

<p>Abstract</p> <p>Objective</p> <p>To determine the prevalence of vertebral fractures (VFs) after 5 years of disease activity score (DAS)-steered treatment in patients with early rheumatoid arthritis (RA) and to investigate the association of VFs with disease activity, functional ability and bone mineral density (BMD) over time.</p> <p>Methods</p> <p>Five-year radiographs of the spine of 275 patients in the BeSt study, a randomized trial comparing four treatment strategies, were used. Treatment was DAS-steered (DAS ≤ 2.4). A height reduction >20% in one vertebra was defined a vertebral fracture. With linear mixed models, DAS and Health Assessment Questionnaire (HAQ) scores over 5 years were compared for patients with and without VFs. With generalized estimating equations the association between BMD and VFs was determined.</p> <p>Results</p> <p>VFs were observed in 41/275 patients (15%). No difference in prevalence was found when stratified for gender, prednisone use and menopausal status. Disease activity over time was higher in patients with VFs, mean difference 0.20 (95% CI: 0.05-0.36), and also HAQ scores were higher, independent of disease activity, with a mean difference of 0.12 (95% CI: 0.02-0.2). Age was associated with VFs (OR 1.06, 95% CI: 1.02-1.09), mean BMD in spine and hip over time were not (OR 95% CI, 0.99: 0.78-1.25 and 0.94: 0.65-1.36, respectively).</p> <p>Conclusion</p> <p>After 5 years of DAS-steered treatment, 15% of these RA patients had VFs. Higher age was associated with the presence of VFs, mean BMD in hip and spine were not. Patients with VFs have greater functional disability over time and a higher disease activity, suggesting that VFs may be prevented by optimal disease activity suppression.</p