Change In DAS28 Research Articles

FRI0039 Modulation of the ACPA Fine Specificity in Patients with RA Treated with Either Abatacept or Adalimumab in the AMPLE Study

BackgroundAnti-citrullinated protein antibodies (ACPAs) are markers of RA and emerging evidence suggests they may play a role in disease progression. Analysis of biomarkers from AMPLE provides a unique opportunity to...

THU0144 The Influence of the Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism on Methotrexate Treatment Outcome in Patients with Rheumatoid Arthritis in the EAST Bohemian Region

BackgroundIdentifying genetic predictors of methotrexate (MTX) therapy response in patients with rheumatoid arthritis (RA) may have importance for clinical benefit optimalization. MTX therapeutic effect is achieved by inhibiting enzymes of...

Association of FCGR2A with the response to infliximab treatment of patients with rheumatoid arthritis

We aimed to assess a functional polymorphism in FCGR2A H131R, for association with the treatment response to Fc-containing inhibitors of tumor necrosis factor (TNF). A total of 429 biologic-naive patients with rheumatoid arthritis collected in two sets (299 and 130) were treated during standard care with infliximab (INX), etanercept, or adalimumab. Response to the treatment was evaluated at 3, 6, and 12 months of follow-up as the change in the Disease Activity Score (DAS) 28 from baseline and as the response by the European League Against Rheumatism (EULAR) criteria. These variables were analyzed for association with linear and logistic regression models that included sex, inhibitors of TNF, and baseline DAS28 as covariates. Significant association was found between the FCGR2A H131R polymorphism and the response to treatment with INX, but not with the other two TNF inhibitors. The 131R allele was associated with a lower change in DAS28 (P=0.04-0.008 at different times) in the first set of patients and confirmed in the second group of patients (P=0.026 at 3 months of follow-up). Association was also found in the comparison between nonresponders and responders to INX by the EULAR criteria. We found an association of the FCGR2A 131R allele with poor response to INX. This finding could be of utility to understand the mechanisms behind treatment failure and contribute to biomarker panels for INX response prediction.

Are there differences between young- and older-onset early inflammatory arthritis and do these impact outcomes? An analysis from the CATCH cohort

The aim of this study was to determine the impact of age on disease and remission in suspected early RA (ERA). Data from the Canadian Early Arthritis Cohort (CATCH) were examined at baseline, 6 and 12 months. Patients were divided into three groups based on age. Analysis of variance (ANOVA) and regression models were performed to determine the impact of age on the 28-joint DAS (DAS28) and remission at 12 months. A total of 1809 patients were initially assessed: 442 (24.4%) young (<42 years), 899 (49.7%) middleaged (542<64 years) and 468 (25.9%) old (564 years); 72.9% female; 63.8% met 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA; symptom duration at first visit 186.0 days; DAS28 4.9; HAQ 1.0; 25.3% had baseline erosions. A significant correlation existed between older age and a lower percentage of females, less positive RF and CCP, fewer meeting RA criteria, shorter symptom duration, more erosions at first visit, higher DAS28 and HAQ at baseline and 12 months and fewer DAS28 remission at 12 months (all P<0.003). The age group did not affect the change in DAS28 and HAQ from 0 to 12 months. Co-morbidities increased with age; more DMARDs, including MTX and steroids, and fewer biologics were used in older age. Age and female had a lesser chance of remission in the regression model. In suspected ERA, older-onset patients start and end their first year worse in terms of DAS28 and HAQ, with fewer meeting RA criteria, less remission, more DMARDs and steroids use but less biologics use. However, there were no differences between age groups in the change in DAS28.

Effect of immunogenicity on efficacy of long-term treatment of rheumatoid arthritis with adalimumab

BackgroundAdalimumab is a monoclonal antibody that targets the inflammatory cytokine tumour necrosis factor α and is effective in the treatment of rheumatoid arthritis. However efficacy of treatment with monoclonal antibodies can decrease over time after initial response. One explanation is the development of immunogenicity leading to the development of antibodies against the drug. Radioimmunoassay (RIA) is a sensitive method to detect anti-drug antibodies and has been previously reported to predict long-term efficacy. Our aim was to evaluate the occurrence of antibodies against adalimumab in a cohort of patients with rheumatoid arthritis followed longitudinally from therapy initiation and to test the association with treatment response. MethodsIn a prospective, multicentre study, serum samples from patients with rheumatoid arthritis treated with adalimumab were collected at 3, 6, and 12 months after treatment initiation. Antibodies to adalimumab were measured with RIA at each timepoint, with the disease activity score in 28 joints (DAS28) measured at baseline and each visit (high disease activity >5·1, moderate 3·2–5·1, low <3·2, in remission <2·6). The change in DAS28 scores at 12 months from baseline was defined as the primary outcome. Findings125 adalimumab-treated patients were available with clinical and biological samples at 3, 6, and 12 months for evaluation of immunogenicity. Mean age was 56 years (SD 12, 70% women). At treatment onset with adalimumab, most patients had never previously received a biological drug (112/125 [90%]), with 109 patients (87%) receiving concomitant disease modifying treatment. Mean DAS28 score at baseline was 5·8 (SD 0·3). Anti-adalimumab antibodies were detected in 31 patients (24%) at one or more timepoints after 12 months of treatment. By 12 months, patients who had developed anti-drug antibodies showed less improvement in disease activity than did patients without antibodies (mean change in DAS28=2·35, 95% CI 1·67–3·03 vs 3·15, 2·86–3·35; p=0·022). InterpretationSerum antibodies against adalimumab are associated with poorer response to treatment in rheumatoid arthritis. Anti-drug antibodies were detected using RIA, even though trough serum samples were not always obtained, reflecting a pragmatic clinical approach. Pharmacological monitoring to detect anti-drug antibodies in patients with rheumatoid arthritis on monoclonal antibody biological therapy might be useful in the prediction of long-term treatment response. FundingUK Medical Research Council [grant number G1000417/94909], ICON, GlaxoSmithKline, AstraZeneca, the Medical Evaluation Unit, Arthritis Research UK (grant number 20385).

Lack of validation of genetic variants associated with anti–tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis

IntroductionIn this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations.MethodsThe four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients.ResultsNone of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis.ConclusionOur data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes.

Ultrasound evaluation of synovitis in RA: Correlation with clinical disease activity and sensitivity to change in an observational cohort study

ObjectiveTo evaluate the correlation between clinical measures of disease activity and a ultrasound (US) scoring system for synovitis applied by many different ultrasonographers in a daily routine care setting within the Swiss registry for RA (SCQM) and further to determine the sensitivity to change of this US Score. MethodsOne hundred and eight Swiss rheumatologists were trained in performing the Swiss Sonography in Arthritis and Rheumatism (SONAR) score. US B-mode and Power Doppler (PwD) scores were correlated with DAS28 and compared between the clinical categories in a cross-sectional cohort of patients. In patients with a second US (longitudinal cohort), we investigated if change in US score correlated with change in DAS and evaluated the responsiveness of both methods. ResultsIn the cross-sectional cohort with 536 patients, correlation between the B-mode score and DAS28 was significant but modest (Pearson coefficient r=0.41, P<0.0001). The same was true for the PwD score (r=0.41, P<0.0001). In the longitudinal cohort with 183 patients we also found a significant correlation between change in B-mode and in PwD score with change in DAS28 (r=0.54, P<0.0001 and r=0.46, P<0.0001, respectively). Both methods of evaluation (DAS and US) showed similar responsiveness according to standardized response mean (SRM). ConclusionsThe SONAR Score is practicable and was applied by many rheumatologists in daily routine care after initial training. It demonstrates significant correlations with the degree of as well as change in disease activity as measured by DAS. On the level of the individual, the US score shows many discrepancies and overlapping results exist.

Dose REduction strategy of subcutaneous TNF inhibitors in rheumatoid arthritis: design of a pragmatic randomised non inferiority trial, the DRESS study

BackgroundPreliminary, mostly uncontrolled studies suggest that dose reduction or discontinuation of tumour necrosis factor blockers can be achieved in a relevant proportion of patients with RA without loss of disease control. However, long term safety, cost effectiveness and feasibility in clinical practice remain uncertain.Methods/DesignThis study is a 18-months pragmatic, non-inferiority, cost minimalisation, randomized controlled trial on dose reduction and discontinuation of the subcutaneous tumour necrosis factor (TNF) blockers adalimumab and etanercept in RA patients with low disease activity. 180 RA patients with low disease activity (DAS28 < 3.2 or clinical judgment of the rheumatologist) are randomized 2:1 to either increased spacing and eventually discontinuation after 6 months of the TNF blocker, and usual care. Implementation is done in routine daily care, using treat to target and feedback implementation in both treatment arms. The primary outcome is non-inferiority (NI margin 20%) in cumulative incidence of persistent (> 3 months) RA flare, according to a recently validated DAS28 based flare criterion (DAS28 change > 1.2, or DAS28 increase of 0.6 and current DAS28 ≥ 3.2). Secondary outcomes include mean disease activity, function, radiographic progression, safety and cost effectiveness. Cost per quality adjusted life year (QALY) differences between groups are expressed as a decremental cost effectiveness ratio (DCER), i.e. saved costs divided by (possible) loss in QALY.DiscussionThe design of this study targeted several clinical and methodological issues on TNF blocker dose de-escalation, including how to taper the TNF blockers, the satisfactory control condition, how to define flare, implementation in clinical practice, and the choice of the non-inferiority margin. Pragmatic cost minimalisation studies using non-inferiority designs and DCERs will become more mainstream as cost effectiveness in healthcare gains importance.Trial registrationDutch Trial Register NTR3216, The study has received ethical review board approval (number NL37704.091.11)

Determining Best Practices in Early Rheumatoid Arthritis by Comparing Differences in Treatment at Sites in the Canadian Early Arthritis Cohort

To determine site variation by comparing outcomes across sites in an early rheumatoid arthritis cohort. Sites from the Canadian Early Arthritis Cohort database with at least 40 patients were studied. Comparisons were made among sites in change in 28-joint Disease Activity Score (DAS28), proportion of patients in DAS28 remission, and treatment strategies. The study included 1138 baseline patients at 8 sites, with baseline (SD) age 52 years (16.9); 72% women; 23% erosions; 54% ever smokers; 51% rheumatoid factor-positive; 37% anticitrullinated protein antibody-positive; disease duration 187 (203) days; DAS28 4.5 (1.4). Site had an effect on outcomes when adjusting for confounders. At 6 and 12 months, sites B and H, the 2 largest sites, had the best changes in DAS28 (-1.82 and -2.09, respectively, at 6 mos, and -2.27 for both at 12 mos; p < 0.001). Site H had the most patients in DAS28 remission at 6 months [64.5% compared to other sites that had from 34.1% to 51.7% (p < 0.001)], and at the last followup, sites B and H had the most in remission. Subcutaneous methotrexate was used more overall and earlier at sites B and H. Those sites used less steroid therapy, and site B had the second-highest use of triple disease-modifying antirheumatic drugs at any visit. Medications were increased more in 2 of the 3 smallest sites. Biologics were used by 9 months most in the smallest (50.0%) and then largest (19.6%) sites. Sites in an early inflammatory arthritis cohort yielded different outcomes. Better outcomes up to 12 months may result from initial treatment with early combination therapy and/or subcutaneous methotrexate.

The outcome and cost-effectiveness of nurse-led care in people with rheumatoid arthritis: a multicentre randomised controlled trial

ObjectiveTo determine the clinical effectiveness and cost-effectiveness of nurse-led care (NLC) for people with rheumatoid arthritis (RA).MethodsIn a multicentre pragmatic randomised controlled trial, the assessment of clinical effects followed a...

Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis

BackgroundIdentification of parameters for early diagnosis and treatment response would be beneficial for patients with early rheumatoid arthritis (ERA) to prevent ongoing joint damage. miRNAs have features of potential biomarkers,...

Therapies for Active Rheumatoid Arthritis after Methotrexate Failure

BackgroundFew blinded trials have compared conventional therapy consisting of a combination of disease-modifying antirheumatic drugs with biologic agents in patients with rheumatoid arthritis who have active disease despite treatment with methotrexate — a common scenario in the management of rheumatoid arthritis.MethodsWe conducted a 48-week, double-blind, noninferiority trial in which we randomly assigned 353 participants with rheumatoid arthritis who had active disease despite methotrexate therapy to a triple regimen of disease-modifying antirheumatic drugs (methotrexate, sulfasalazine, and hydroxychloroquine) or etanercept plus methotrexate. Patients who did not have an improvement at 24 weeks according to a prespecified threshold were switched in a blinded fashion to the other therapy. The primary outcome was improvement in the Disease Activity Score for 28-joint counts (DAS28, with scores ranging from 2 to 10 and higher scores indicating more disease activity) at week 48.ResultsBoth groups had significant improvement over the course of the first 24 weeks (P=0.001 for the comparison with baseline). A total of 27% of participants in each group required a switch in treatment at 24 weeks. Participants in both groups who switched therapies had improvement after switching (P<0.001), and the response after switching did not differ significantly between the two groups (P=0.08). The change between baseline and 48 weeks in the DAS28 was similar in the two groups (−2.1 with triple therapy and −2.3 with etanercept and methotrexate, P=0.26); triple therapy was noninferior to etanercept and methotrexate, since the 95% upper confidence limit of 0.41 for the difference in change in DAS28 was below the margin for noninferiority of 0.6 (P=0.002). There were no significant between-group differences in secondary outcomes, including radiographic progression, pain, and health-related quality of life, or in major adverse events associated with the medications.ConclusionsWith respect to clinical benefit, triple therapy, with sulfasalazine and hydroxychloroquine added to methotrexate, was noninferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy. (Funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others; CSP 551 RACAT ClinicalTrials.gov number, NCT00405275.)

Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy. Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28. In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28. In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

FRI0077 Levels of mir-16 in serum associate with response to therapy in patients with early rheumatoid arthritis

BackgroundStudies have shown a beneficial effect of early treatment on clinical outcome and reduction in joint damage in patients with rheumatoid arthritis (RA). MiRNAs are stably present in cell-free form...

SAT0145 Timing and magnitude of initial response to certolizumab pegol in a broad population of patients with active rheumatoid arthritis predicts likelihood of LDA at week 28

BackgroundIt has previously been shown that the majority of patients (pts) with active rheumatoid arthritis (RA) have a rapid response to certolizumab pegol (CZP) and that lack of improvement in...

FRI0046 Characterization of nitrotyrosine as a clinical biomarker for arthritis and joint injury

BackgroundIncreased nitric oxide synthase (NOS) activity has been linked to joint injury and is associated with increased chondrocyte apoptosis, increased matrix metalloproteinase (MMP) activity, and decreased extracellular matrix synthesis. Osteoarthritis...

THU0174 Impact of IL-6R and IL-6ST Polymorphisms on Response to Anti-TNF Therapy in UK Patients – Results from the Braggss Cohort

BackgroundAnti-tumour necrosis factor (anti-TNF) biologic therapy is a highly effective yet expensive treatment for patients with Rheumatoid Arthritis (RA). Patient eligibility for therapy and response to treatment is assessed using...

AB0521 A single-arm, open-label study of the safety and effectiveness of tocilizumab in combination with methotrexate, in patients with rheumatoid arthritis in latin america – preliminary effectiveness results-ritmo study

ObjectivesTo present the preliminary effectiveness data of TCZ + MTX treatment, with regard to reduction in signs and symptoms over 6 months in Latin American pts with mod/severe RA, MTX-IR.MethodsRitmo...

AB0562 A double-blind, placebo-controlled, multicenter trial of tocilizumab in moderate to severe active RA patients with inadequate response to methotrexate in korean population

BackgroundInterleukin-6 (IL-6), a proinflammatory cytokine, is thought to play a major pathological role in rheumatoid arthritis (RA). Tocilizumab is humanized anti IL-6 receptor monoclonal antibody which has been shown to...

AB0571 Efficacy of tocilizumab prescribed as first line biologic: A 48-week post marketing observational study in romanian rheumatoid arthritis patients (stone) - interim analysis

BackgroundOptimal care of patients with Rheumatoid Arthritis (RA) requires an integrated approach of pharmacologic therapies which usually includes conventional DMARD’s and biological DMARD’s such as Tocilizumab (TCZ). In Romania, official...