Adherence to a treat-to-target strategy in early rheumatoid arthritis:results of the DREAM remission induction cohort

INTRODUCTION: Clinical trials have demonstrated that treatment-to-target (T2T) is effective in achieving remission in early rheumatoid arthritis (RA). However, the concept of T2T has not been fully implemented yet and the question is whether a T2T strategy is feasible in daily clinical practice. The objective of the study was to evaluate the adherence to a T2T strategy aiming at remission (Disease Activity Score in 28 joints (DAS28) < 2.6) in early RA in daily practice. The recommendations regarding T2T included regular assessment of the DAS28 and advice regarding DAS28-driven treatment adjustments. METHODS: A medical chart review was performed among a random sample of 100 RA patients of the DREAM remission induction cohort. At all scheduled visits, it was determined whether the clinical decisions were compliant to the T2T recommendations. RESULTS: The 100 patients contributed to a total of 1,115 visits. The DAS28 was available in 97.9% (1,092/1,115) of the visits, of which the DAS28 was assessed at a frequency of at least every three months in 88.3% (964/1,092). Adherence to the treatment advice was observed in 69.3% (757/1,092) of the visits. In case of non-adherence when remission was present (19.5%, 108/553), most frequently medication was tapered off or discontinued when it should have been continued (7.2%, 40/553) or treatment was continued when it should have been tapered off or discontinued (6.2%, 34/553). In case of non-adherence when remission was absent (42.1%, 227/539), most frequently medication was not intensified when an intensification step should have been taken (34.9%, 188/539). The main reason for non-adherence was discordance between disease activity status according to the rheumatologist and DAS28. CONCLUSIONS: The recommendations regarding T2T were successfully implemented and high adherence was observed. This demonstrates that a T2T strategy is feasible in RA in daily clinical practice

Psychophysiological Responses to Stress after Stress Management Training in Patients with Rheumatoid Arthritis

Contains fulltext : 97274.pdf (publisher's version ) (Open Access)BACKGROUND: Stress management interventions may prove useful in preventing the detrimental effects of stress on health. This study assessed the effects of a stress management intervention on the psychophysiological response to stress in patients with rheumatoid arthritis (RA). METHODS: Seventy-four patients with RA, who were randomly assigned to either a control group or a group that received short-term stress management training, performed a standardized psychosocial stress task (Trier Social Stress Test; TSST) 1 week after the stress management training and at a 9-week follow-up. Psychological and physical functioning, and the acute psychophysiological response to the stress test were assessed. RESULTS: Patients in the intervention group showed significantly lower psychological distress levels of anxiety after the training than did the controls. While there were no between-group differences in stress-induced tension levels, and autonomic (alpha-amylase) or endocrine (cortisol) responses to the stress test 1 week after the intervention, levels of stress-induced tension and cortisol were significantly lower in the intervention group at the 9-week follow-up. Overall, the response to the intervention was particularly evident in a subgroup of patients with a psychological risk profile. CONCLUSION: A relatively short stress management intervention can improve psychological functioning and influences the psychophysiological response to stress in patients with RA, particularly those psychologically at risk. These findings might help understand how stress can affect health and the role of individual differences in stress responsiveness. TRIAL REGISTRATION: TrialRegister.nl NTR1193

Effectiveness of tocilizumab with and without synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis : results from a European collaborative study

Objectives To examine the effectiveness of tocilizumab (TCZ) with and without synthetic disease-modifying antirheumatic drugs (sDMARDs) in a large observational study. Methods Patients with rheumatoid arthritis treated with TCZ who had a baseline visit and information on concomitant sDMARDs were included. According to baseline data, patients were considered as taking TCZ as monotherapy or combination with sDMARDs. Main study outcomes were the change of Clinical Disease Activity Index (CDAI) and TCZ retention. The prescription of TCZ as monotherapy was analysed using logistic regression. CDAI change was analysed with a mixed-effects model for longitudinal data. TCZ retention was analysed with a stratified extended Cox model. Results Multiple-adjusted analysis suggests that prescription of TCZ as monotherapy varied according to age, corticosteroid use, country of the registry and year of treatment initiation. The change of disease activity assessed by CDAI as well as the likelihood to be in remission were not significantly different whether TCZ was used as monotherapy or in combination with sDMARDs in a covariate-adjusted analysis. Estimates for unadjusted median TCZ retention were 2.3 years (95% CI 1.8 to 2.7) for monotherapy and 3.7 years (lower 95% CI limit 3.1, upper limit not estimable) for combination therapies. In a covariate-adjusted analysis, TCZ retention was also reduced when used as monotherapy, with an increasing difference between mono and combination therapy over time after 1.5 years (p=0.002). Conclusions TCZ with or without concomitant sDMARDs resulted in comparable clinical response as assessed by CDAI change, but TCZ retention was shorter under monotherapy of TCZ.Peer reviewe

The EULAR Study Group for Registers and Observational Drug Studies: comparability of the patient case mix in the European biologic disease modifying anti-rheumatic drug registers

Objective. Under the auspices of the European League Against Rheumatism (EULAR), a study group of investigators representing European biologic DMARD (bDMARD) registers was convened. The purpose of this initial assessment was to collect and compare a cross section of patient characteristics and collate information on the availability of potential confounders within these registers. Methods. Baseline characteristics of patients starting their first bDMARD in an arbitrary year (2008) for the treatment of RA, including demographic and disease characteristics, bDMARD drug details and co-morbidities, were collected and compared across 14 European bDMARD registers. Results. A total of 5320 patients were included. Half the registers had restricted recruitment to certain bDMARDs during the study year. All registers's collected data on age, gender, disease duration, seropositivity for IgM-RF and 28-joint DAS (DAS28). The mean DAS28 ranged from 4.2 to 6.6 and the mean HAQ from 0.8 to 1.9. Current smoking ranged from 9% to 34%. Nine registers reported co-morbidities with varying prevalence. Conclusion. In addition to demonstrating European-wide collaboration across rheumatology bDMARD registers, this assessment identified differences in prescribing patterns, recruitment strategies and data items collected. These differences need to be considered when applying strategies for combined analysis. The lack of a common data model across Europe calls for further work to harmonize data collection across register

Personal non-commercial use only

ABSTRACT. Objective. To compare the psychometric functioning of multidimensional disease-specific, multiitem generic, and single-item measures of fatigue in patients with rheumatoid arthritis (RA). Methods. Confirmatory factor analysis (CFA) and longitudinal item response theory (IRT) modeling were used to evaluate the measurement structure and local reliability of the Bristol RA Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the Medical Outcomes Study Short Form-36 (SF-36) vitality scale, and the BRAF Numerical Rating Scales (BRAF-NRS) in a sample of 588 patients with RA. Results. A 1-factor CFA model yielded a similar fit to a 5-factor model with subscale-specific dimensions, and the items from the different instruments adequately fit the IRT model, suggesting essential unidimensionality in measurement. The SF-36 vitality scale outperformed the BRAF-MDQ at lower levels of fatigue, but was less precise at moderate to higher levels of fatigue. At these levels of fatigue, the living, cognition, and emotion subscales of the BRAF-MDQ provide additional precision. The BRAF-NRS showed a limited measurement range with its highest precision centered on average levels of fatigue. Conclusion. The different instruments appear to access a common underlying domain of fatigue severity, but differ considerably in their measurement precision along the continuum. The SF-36 vitality scale can be used to measure fatigue severity in samples with relatively mild fatigue. For samples expected to have higher levels of fatigue, the multidimensional BRAF-MDQ appears to be a better choice. The BRAF-NRS are not recommended if precise assessment is required, for instance in longitudina

Fatigue assessment in RA Personal non-commercial use only

ABSTRACT. Objective. To compare the psychometric functioning of multidimensional disease-specific, multiitem generic, and single-item measures of fatigue in patients with rheumatoid arthritis (RA). Methods. Confirmatory factor analysis (CFA) and longitudinal item response theory (IRT) modeling were used to evaluate the measurement structure and local reliability of the Bristol RA Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ), the Medical Outcomes Study Short Form-36 (SF-36) vitality scale, and the BRAF Numerical Rating Scales (BRAF-NRS) in a sample of 588 patients with RA. Results. A 1-factor CFA model yielded a similar fit to a 5-factor model with subscale-specific dimensions, and the items from the different instruments adequately fit the IRT model, suggesting essential unidimensionality in measurement. The SF-36 vitality scale outperformed the BRAF-MDQ at lower levels of fatigue, but was less precise at moderate to higher levels of fatigue. At these levels of fatigue, the living, cognition, and emotion subscales of the BRAF-MDQ provide additional precision. The BRAF-NRS showed a limited measurement range with its highest precision centered on average levels of fatigue. Conclusion. The different instruments appear to access a common underlying domain of fatigue severity, but differ considerably in their measurement precision along the continuum. The SF-36 vitality scale can be used to measure fatigue severity in samples with relatively mild fatigue. For samples expected to have higher levels of fatigue, the multidimensional BRAF-MDQ appears to be a better choice. The BRAF-NRS are not recommended if precise assessment is required, for instance in longitudinal settings. (J Rheumatol First Release Jan 15 2015

The relationship between change in subjective outcome and change in disease: a potential paradox

Contains fulltext : 87756.pdf (publisher's version ) (Closed access)BACKGROUND: Response shift theory suggests that improvements in health lead patients to change their internal standards and re-assess former health states as worse than initially rated when using retrospective ratings via the then-test. The predictions of response shift theory can be illustrated using prospect theory, whereby a change in current health causes a change in reference frame. Therefore, if health deteriorates, the former health state will receive a better rating, whereas if it improves, the former health state will receive a worse rating. OBJECTIVE: To explore the predictions of response shift and prospect theory by relating subjective change to objective change. METHODS: Baseline and 3-month follow-up data from a cohort of rheumatoid arthritis patients (N = 197) starting on TNFalpha-blocking agents were used. Objective disease change was classified according to a disease-specific clinical outcome measure (DAS28). Visual analogue scales (VAS) for general health (GH) and pain were used as self-reported measures. Three months after starting on anti-TNFalpha, patients used the then-test to re-rate their baseline health with regard to general health and pain. Differences between then-test value and baseline values were calculated and tested between improved, non-improved and deteriorated patients by the Student t-test. RESULTS: At 3 months, 51 (25.9%) patients had good improvement in health, 83 (42.1%) had moderate improvement, and 63 (32.0%) had no improvement or deteriorated in health. All patients no matter whether they improved, did not improve, or even became worse rated their health as worse retrospectively. The difference between the then-test rating and the baseline value was similarly sized in all groups. CONCLUSION: More positive ratings of retrospective health are independent of disease change. This suggests that patients do not necessarily change their standards in line with their disease change, and therefore it is inappropriate to use the then-test to correct for such a change. If a then-test is used to correct for shifts in internal standards, it might lead to the paradoxical result that patients who do not improve or even deteriorate increase significantly on self-reported health and pain. An alternative explanation for differences in retrospective and prospective ratings of health is the implicit theory of change which is more successful in explaining our results than prospect theory.1 september 201

A Replication Study of the Association between Rheumatoid Arthritis and Deletion of the Late Cornified Envelope Genes LCE3B and LCE3C

OBJECTIVE: Two recent studies, in a Spanish and a Chinese population, point to an association between rheumatoid arthritis (RA) risk and the deletion of the Late Cornified Envelope (LCE) 3B and 3C genes (LCE3C_LCE3B-del), a known risk factor for psoriasis. We aimed to replicate these studies in a large Dutch cohort. METHODS: 1039 RA cases and 759 controls were genotyped for LCE3C_LCE3B-del. Association analysis was performed for the complete cohort and after stratification for the serologic markers anti-cyclic citrullinated peptide and rheumatoid factor. A meta-analysis was performed combining our data with the Spanish and Chinese datasets, resulting in an analysis including 2466 RA cases and 2438 controls. RESULTS: In the Dutch cohort we did not observe a significant association of LCE3C_LCE3B-del (p = 0.093) with RA risk. A stratified analysis for the serologic positive and negative group did not show an association between the genetic variant and disease risk, either. The meta-analysis, however, confirmed a significant association (p<0.0001, OR = 1.31, 95% confidence interval 1.16-1.47). CONCLUSION: Our meta-analysis confirms the association of the LCE3 deletion with RA, suggesting that LCE3C_LCE3B-del is a common risk factor for (auto)immune diseases

Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort : data from the CERERRA collaboration

Background: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg x 2, but some data have suggested similar clinical efficacy with 500 mg x 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. Methods: Twelve European registries participating in the CERERRA collaboration (The European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis) submitted anonymized datasets with demographic, efficacy and treatment data for patients who had started RTX. Treatment effectiveness was assessed by DAS28 reductions and EULAR responses after 6 months. Results: Data on RTX dose were available for 2,873 patients, of whom 2,625 (91.4 %) and 248 (8.6 %) received 1000 mg x 2 and 500 mg x 2, respectively. Patients treated with 500 mg x 2 were significantly older, had longer disease duration, higher number of prior DMARDs, but lower number of prior biologics and lower baseline DAS28 than those treated with 1000 mg x 2. Fewer patients in the low-dose group received concomitant DMARDs but more frequently received concomitant corticosteroids. Both doses led to significant clinical improvements at 6 months. DAS28 reductions at 6 months were comparable in the 2 dose regimens [mean DeltaDAS28 +/- SD -2.0 +/- 1.3 (high dose) vs. -1.7 +/- 1.4 (low dose), p = 0.23 adjusted for baseline differences]. Similar percentages of patients achieved EULAR good response in the two dose groups, 18.4 % vs. 17.3 %, respectively (p = 0.36). Conclusions: In this large observational cohort initial treatment with RTX at 500 mg x 2 and 1000 mg x 2 led to comparable clinical outcomes at 6 months.Peer reviewe

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al