Background Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA).... Show moreBackground Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). Objective To develop recommendations for achieving optimal therapeutic outcomes in RA. Methods A task force of rheumatologists and a patient developed a set of recommendations on the basis of evidence derived from a systematic literature review and expert opinion; these were subsequently discussed, amended and voted upon by >60 experts from various regions of the world in a Delphi-like procedure. Levels of evidence, strength of recommendations and levels of agreement were derived. Results The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow-up (every 1-3 months during active disease) with appropriate therapeutic adaptation to reach the desired state within 3 to a maximum of 6 months was recommended. Follow-up examinations ought to employ composite measures of disease activity which include joint counts. Additional items provide further details for particular aspects of the disease. Levels of agreement were very high for many of these recommendations (>= 9/10). Conclusion The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion. Show less
Objectives To summarise existing evidence on a target oriented approach for rheumatoid arthritis (RA) treatment. Methods We conducted a systematic literature search including all clinical trials... Show moreObjectives To summarise existing evidence on a target oriented approach for rheumatoid arthritis (RA) treatment. Methods We conducted a systematic literature search including all clinical trials testing clinical, functional, or structural values of a targeted treatment approach. Our search covered Medline, Embase and Cochrane databases until December 2008 and also conference abstracts (2007, 2008). Results The primary search yielded 5881 citations; after the selection process, 76 papers underwent detailed review. Of these, only seven strategic clinical trials were extracted: four studies randomised patients to routine or targeted treatment, two compared two different randomised targets and one compared targeted treatment to a historical control group. Five trials dealt with early RA patients. All identified studies showed significantly better clinical outcomes of targeted approaches than routine approaches. Disability was reported in two studies with no difference between groups. Four studies compared radiographic outcomes, two showing significant benefit of the targeted approach. Conclusion Only few studies employed randomised controlled settings to test the value of treatment to a specific target. However, they provided unanimous evidence for benefits of targeted approaches. Nevertheless, more data on radiographic and functional outcomes and on patients with established RA are needed. Show less
Lie, E.; Heijde, D. van der; Uhlig, T.; Heiberg, M.S.; Koldingsnes, W.; Rodevand, E.; ... ; Kvien, T.K. 2010
Objective To examine the effectiveness and 2-year retention rates of methotrexate (MTX) in MTX naive patients with psoriatic arthritis (PsA). Methods Data on 430 patients with PsA participating in... Show moreObjective To examine the effectiveness and 2-year retention rates of methotrexate (MTX) in MTX naive patients with psoriatic arthritis (PsA). Methods Data on 430 patients with PsA participating in an ongoing longitudinal observational multicentre study in Norway were analysed. 1218 MTX naive patients with rheumatoid arthritis (RA) from the same study served as a reference population. Assessments included measures of disease activity (28 joint counts, acute phase reactants), health status and utility scores. Six-month effectiveness data were compared both by crude analyses and with adjustments for age, sex and the respective baseline values. Two-year drug survival was compared by Kaplan-Meier and Cox regression analyses. Results After 6 months of MTX treatment, both patients with PsA and those with RA improved in most disease activity measures and patient reported outcomes. In the adjusted analysis, patients with PsA tended to have less improvement, but changes were in the same range as in patients with RA. Two-year retention rates of MTX therapy in patients with PsA and RA were 65% and 66%, respectively, with only minor differences in reported reasons for discontinuation. Lower age, longer disease duration and higher Modified Health Assessment Questionnaire (MHAQ) score and patient global assessment were independent predictors of MTX termination within the first 2 years of treatment. Conclusion In this real-life study, MTX treatment was associated with improvement in disease activity and health-related quality of life in patients with PsA after 6 months of treatment. Retention rates of MTX were similar in PsA and RA. Show less
Heijde, D. van der; Braun, J.; Sieper, J.; Wishneski, C.; Vlahos, B.; Szumski, A.; ... ; Koenig, A. 2010
Objective. To determine the validity, reliability and responsiveness of the Work Productivity and Activity Impairment questionnaire in AS (WPAI:SpA). Methods. Baseline and Week-24 data from a... Show moreObjective. To determine the validity, reliability and responsiveness of the Work Productivity and Activity Impairment questionnaire in AS (WPAI:SpA). Methods. Baseline and Week-24 data from a randomized, double-blind study of adalimumab in patients with AS were used. Discriminative validity of WPAI: SpA absenteeism, presenteeism, overall work productivity loss and activity impairment scores was assessed relative to patient-reported outcomes: Bath AS Disease Activity Index (BASDAI), AS Quality of Life Questionnaire (ASQOL), Short-Form 36 Health Survey (SF-36), Physical and Mental Component Summaries (PCS and MCS, respectively) and Health Utilities Index Mark 3 (HUI-3). Responsiveness of the WPAI: SpA instrument was assessed for patients meeting the minimum clinically important differences (MCIDs) for ASQOL and BASDAI (i.e. quality of life and clinical responders, respectively) and quantified with standardized response mean (SRM) calculations. Results. Of 315 patients, 205 were employed at baseline. Patients with more severe AS (BASDAI > median) showed significantly greater impairment in work and daily activities than patients with lesser disease severity (P < 0.001). This trend was consistent for ASQOL, SF-36 PCS, SF-36 MCS and HUI-3. There were significant differences in WPAI: SpA scores for patients achieving BASDAI clinical response and ASQOL quality of life response vs non-responders. For responders, SRMs were large for work presenteeism, overall work impairment and activity impairment (-0.86 to -1.29 for BASDAI; -0.89 to -1.18 for ASQOL) and small for absenteeism (-0.25 for BASDAI; -0.31 for ASQOL). Conclusions. The WPAI: SpA is a valid, reliable and responsive tool for assessing work productivity for patients with AS. Show less
Objective. To evaluate how continuation of and alterations to initial year 1 combination etanercept-methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and... Show moreObjective. To evaluate how continuation of and alterations to initial year 1 combination etanercept-methotrexate (MTX) therapy and MTX monotherapy regimens affect long-term remission and radiographic progression in early, active rheumatoid arthritis. Methods. Subjects were randomized at baseline for the entire 2-year period; those who completed 1 year of treatment with combination or MTX monotherapy entered year 2. The original combination group either continued combination therapy (the EM/EM group; n = 111) or received etanercept monotherapy (the EM/E group; n = 111) in year 2; the original MTX monotherapy group either received combination therapy (the M/EM group; n = 90) or continued monotherapy (the M/M group; n = 99) in year 2. Efficacy end points included remission (a Disease Activity Score in 28 joints [DAS28] < 2.6) and radiographic nonprogression (change in the modified Sharp/van der Heijde score <= 0.5) at year 2. A last observation carried forward analysis from the modified intention-to-treat population (n = 398) and a post hoc nonresponder imputation (NRI) analysis (n = 528) were performed for remission. Results. At year 2, DAS28 remission was achieved by 62/108, 54/108, 51/88, and 33/94 subjects in the EM/EM, EM/E, M/EM, and M/M groups, respectively (P < 0.01 for the EM/EM and M/EM groups versus the M/M group). This effect was corroborated by a more conservative post hoc 2-year NRI analysis, with remission observed in 59/131, 50/134, 48/133, and 29/130 of the same respective groups (P < 0.05 for each of the EM/EM, EM/E, and M/EM groups versus the M/M group). The proportions of subjects achieving radiographic nonprogression (n = 360) were 89/99, 74/99, 59/79, and 56/83 in the EM/EM (P < 0.01 versus each of the other groups), EM/E, M/EM, and M/M groups, respectively. No new safety signals or between-group differences in serious adverse events were seen. Conclusion. Early sustained combination etanercept-MTX therapy was consistently superior to MTX monotherapy. Combination therapy resulted in important clinical and radiographic benefits over 2 study years, without significant additional safety risk. Show less
Syversen, S.W.; Goll, G.L.; Heijde, D. van der; Landewe, R.; Lie, B.A.; Odegard, S.; ... ; Kvien, T.K. 2010
Objectives: Anti-citrullinated peptide antibodies (ACPAs) are established as useful predictors of radiographic progression in rheumatoid arthritis (RA). The main objective of this study was to test... Show moreObjectives: Anti-citrullinated peptide antibodies (ACPAs) are established as useful predictors of radiographic progression in rheumatoid arthritis (RA). The main objective of this study was to test the prognostic capacity of the recently developed test for anti-mutated citrullinated vimentin (anti-MCV). Methods: A cohort of 238 patients with RA was followed longitudinally for 10 years; 125 patients with complete x ray sets were included in the main analyses. Radiographs were scored according to the van der Heijde modified Sharp score (SHS). Patients were analysed for anti-MCV and anti-cyclic citrullinated peptide (CCP), and were genotyped for human leukocyte antigen (HLA)-DRB1 "shared epitope'' (SE) and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) 1858T. Results: Anti-MCV and anti-CCP were strongly associated with regard to status and level. Both antibodies were associated with SE, but only anti-MCV was significantly associated with PTPN22 1858T. A positive anti-MCV test increased the odds of radiographic progression by 7.3 (95% confidence interval (CI) 3.2 to 16.5) compared to 5.7 (95% CI 2.6 to 12.5) for a positive anti-CCP. Presence of MCV antibodies gave an average increase in the total SHS of 30 U compared to an average increase of 25 U for the presence of CCP antibodies. Anti-MCVs were more strongly associated to progression in erosions than joint space narrowing. Associations remained after adjustment for other predictors of radiographic progression. The odds of progression increased with increasing anti-MCV level. Conclusions: Presence of anti-MCV predicted joint damage, and the strength of this prediction was at least as strong as for anti-CCP. Antibody status showed a stronger association to bone than to cartilage destruction. This study also indicates that higher anti-MCV levels add prognostic information compared to their mere presence or absence. Show less
Maksymowych, W.P.; Gooch, K.L.; Wong, R.L.; Kupper, H.; Heijde, D. van der 2010
Objective. To determine factors associated with work in patients with ankylosing spondylitis (AS). Methods. Three hundred fifteen patients with AS were enrolled in a 24-week, randomized controlled... Show moreObjective. To determine factors associated with work in patients with ankylosing spondylitis (AS). Methods. Three hundred fifteen patients with AS were enrolled in a 24-week, randomized controlled study Of adalimumab with a longterm, open-label, adalimumab extension phase. Patient-reported outcome (PRO) Measures included the Medical Outcome Study Short Form 36 Health survey (SF-36), AS Quality of Life Questionnaire (ASQOL). Health Utilities Index Mark 3 (HUI-3) and Work Productivity and Activity Impairment-Specific Health Problem Questionnaire (WPAI-SHP). Multivariate logistic regression Was used to analyze differences between working and nonworking patients. The relationships between PRO and WPAI-SHP scores were assessed Using Pearson correlation coefficients. Multivariate modeling was applied to determine factors associated with productivity while at work. WPAI-SHP was assessed through 3 years of adalimumab exposure. Results. Younger age (p = 0.002) and male sex (p < 0.001) were significantly and independently associated with working patients with AS. The SF-36 Physical Component Summary score (p < 0.001). ASQOL score (p < 0.001), HUI-3 scores (p < 0.001). and both Patient's global assessment of disease activity (p < 0.001) and nocturnal pain (p < 0.001) scores were independently associated with working status. Work absenteeism due to AS was weakly correlated with all PRO scores. WPAI-SHP components of work presenteeism (lack of productivity at work), activity impairment, and overall work productivity loss clue to AS were moderately correlated with quality of life as measured by file ASQOL, the SF-36 Physical Component Summary score, and the SF-36 Bodily Pain domain. Linear multivariate analyses indicated that work presenteeism was significantly associated with pain, functioning and disease activity. Longterm adalimumab treatment was associated With sustained improvements in WPAI-SHP scores. Conclusions. Quality of life and the Physical consequences associated with AS have a direct relationship with a patient's ability to work. Adalimumab sustains improvements in work outcomes in patients with AS. (First Release Dec 1 2009; J Rheumatol 2010:37:385-92 doi: 10.3999/jrheum.090242) Show less
Boonen, A.; Braun, J.; Bruinsma, I.E.V.; Huang, F.; Maksymowych, W.; Kostanjsek, N.; ... ; Heijde, D. van der 2010
Objective: To report on the results of a standardised consensus process agreeing on concepts typical and/or relevant when classifying functioning and health in patients with ankylosing spondylitis ... Show moreObjective: To report on the results of a standardised consensus process agreeing on concepts typical and/or relevant when classifying functioning and health in patients with ankylosing spondylitis (AS) based on the International Classification of Functioning and Health (ICF). Methods: Experts in AS from different professional and geographical backgrounds attended a consensus conference and were divided into three working groups. Rheumatologists were selected from members of the Assessment of SpondyloArthritis international Society (ASAS). Other health professionals were recommended by ASAS members. The aim was to compose three working groups with five to seven participants to allow everybody's contribution in the discussions. Experts selected ICF categories that were considered typical and/or relevant for AS during a standardised consensus process by integrating evidence from preceding studies in alternating working group and plenary discussions. A Comprehensive ICF Core Set was selected for the comprehensive classification of functioning and a Brief ICF Core Set for application in trials. Results: The conference was attended by 19 experts from 12 countries. Eighty categories were included in the Comprehensive Core Set, which included 23 Body functions, 19 Body structures, 24 Activities and participation and 14 Environmental factors. Nineteen categories were selected for the Brief Core Set, which included 6 Body functions, 4 Body structures, 7 Activities and participation and 2 Environmental factors. Conclusion: The Comprehensive and Brief ICF Core Sets for AS are now available and aim to represent the external reference to define consequences of AS on functioning. Show less
Hammer, H.B.; Odegard, S.; Syversen, S.W.; Landewe, R.; Heijde, D. van der; Uhlig, T.; ... ; Kvien, T.K. 2010
Background: Plasma levels of calprotectin, a major S100 leucocyte protein, are cross-sectionally associated with clinical and laboratory markers of inflammation and with radiographic damage in... Show moreBackground: Plasma levels of calprotectin, a major S100 leucocyte protein, are cross-sectionally associated with clinical and laboratory markers of inflammation and with radiographic damage in rheumatoid arthritis (RA). High amounts of calprotectin are found in synovial fluid from patients with RA. Objective: To examine whether calprotectin might be an independent predictor of joint destruction over time. Methods: 124 patients with RA were assessed at baseline and after 10 years with inflammatory markers (calprotectin, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)), serological variables (antibodies to cyclic citrullinated peptide (anti-CCP), IgA rheumatoid factor (RF) and IgM RF) and radiographic and clinical assessments of joint damage (hand radiographs and Rheumatoid Arthritis Articular Damage (RAAD) score). Progression of radiographic damage was assessed according to the van der Heijde modified Sharp score. Results: At both examinations the highest calprotectin levels were found in patients positive for anti-CCP, IgA and IgM RF. Calprotectin had moderate to good correlations with inflammatory and serological markers (r=0.41-0.67). Patients with normal baseline calprotectin levels had a lower degree of joint damage. High univariate associations were found between baseline calprotectin levels and progression in the Sharp score as well as the RAAD score. Baseline calprotectin was independently associated with progression in the Sharp score and with the RAAD score in multiple linear regression analyses, including baseline levels of CRP, ESR, anti-CCP in addition to demographic variables. Conclusion: Calprotectin was an independent predictor of clinical and radiographic joint damage after 10 years. These findings support the proposal that calprotectin may be a prognostic biomarker for erosive disease in patients with RA. Show less
