Recently diagnosed rheumatoid arthritis patients benefit from a treat-to-target strategy: results from the DREAM registry

Despite considerable evidence on the efficacy and safety of early aggressive treat-to-target (T2T) strategies in early rheumatoid arthritis (RA), a proportion of patients still fail to reach remission. The goal of this study is to examine remission rates and predictors of remission in a real life T2T cohort of consecutive patients with a recent diagnosis of RA. Baseline demographics, clinical, laboratory and patient-reported variables and 1-year follow-up disease activity data were used from patients with early RA included in the DREAM remission induction cohort II study. Survival analyses and simple and multivariable logistic regression analyses were used to examine remission rates and significant predictors of achieving remission. A total of 137 recently diagnosed consecutive RA patients were available for this study. During the first year after inclusion, DAS28 remission was achieved at least once in 77.2 % of the patients and the median time to first remission was 17 weeks. None of the examined baseline variables were robustly associated with achieving remission within 1 year and in the multivariable analysis only lower ESR (p = 0.005) remained significantly associated with achieving fast remission within 17 weeks. During the first year of their disease a high proportion of recently diagnosed RA patient achieved remission, with only a small percentage of patients needing bDMARD therapy. Combined with the absence of baseline predictors of remission, this suggests that clinicians in daily clinical practice may focus on DAS28 scores only, without needing to take other patients characteristics into account

Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis

ObjectivesPatients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA.MethodsIn 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions.Results5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics).ConclusionsIn a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA

Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for CD40 and CD39

This study was supported by Medical Research Council (MRC) MR/K015346/1 MATURA study. ARUK 20670 MATURA study. Publisher Copyright: © Author(s) (or their employer(s)) 2019.Objectives We sought to investigate whether genetic effects on response to TNF inhibitors (TNFi) in rheumatoid arthritis (RA) could be localised by considering known genetic susceptibility loci for relevant traits and to evaluate the usefulness of these genetic loci for stratifying drug response. Methods We studied the relation of TNFi response, quantified by change in swollen joint counts (ΔSJC) and erythrocyte sedimentation rate (ΔESR) with locus-specific scores constructed from genome-wide assocation study summary statistics in 2938 genotyped individuals: 37 scores for RA; scores for 19 immune cell traits; scores for expression or methylation of 93 genes with previously reported associations between transcript level and drug response. Multivariate associations were evaluated in penalised regression models by cross-validation. Results We detected a statistically significant association between ΔSJC and the RA score at the CD40 locus (p=0.0004) and an inverse association between ΔSJC and the score for expression of CD39 on CD4 T cells (p=0.00005). A previously reported association between CD39 expression on regulatory T cells and response to methotrexate was in the opposite direction. In stratified analysis by concomitant methotrexate treatment, the inverse association was stronger in the combination therapy group and dissipated in the TNFi monotherapy group. Overall, ability to predict TNFi response from genotypic scores was limited, with models explaining less than 1% of phenotypic variance. Conclusions The association with the CD39 trait is difficult to interpret because patients with RA are often prescribed TNFi after failing to respond to methotrexate. The CD39 and CD40 pathways could be relevant for targeting drug therapy.Peer reviewe

Changes in priorities for improvement in patients with rheumatoid arthritis during 1 year of anti-tumour necrosis factor treatment

Objectives: To examine priorities for health status improvement in patients with active rheumatoid arthritis (RA) during anti-tumour necrosis factor (TNF) treatment.\ud \ud Methods: Data were used from 173 patients with RA starting treatment with TNF-blocking agents. Outcome measures included assessment of health status with the Arthritis Impact Measurement Scales 2 (AIMS2) at baseline and after 3 and 12 months. The AIMS2 contains a priority list from which patients are asked to select from 12 areas of health the 3 in which they would most like to see improvement.\ud \ud Results: After 1 year of treatment, 10 out of 12 areas of health on the AIMS2 were significantly improved. The most commonly selected priorities for improvement at baseline were pain (88%), hand and finger function (57%), walking and bending (42%), mobility (33%), and work (29%). At group level, this priority ranking remained largely unchanged during treatment. After adjustment for multiple comparisons, only pain was selected significantly less often at 3 and 12 months (71% at both assessments). Within individual patients, however, priorities often changed. Changes in the priority of pain were related to the achieved level of patient-perceived pain and disease activity.\ud \ud Conclusions: This study shows that, at the group level, patients’ priorities for improvement are fairly stable during 12 months of anti-TNF therapy, despite major improvements in health status. Although pain reduction becomes somewhat less important, it remains the most commonly selected priority. In contrast, individual patient priorities are not stable over the course of treatment and appear to be associated with differences in disease state

Interchangeability of 28-joint disease activity scores using the erythrocyte sedimentation rate or the C-reactive protein as inflammatory marker

This paper aims to examine the interchangeability of the disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores in a diverse sample of rheumatoid arthritis (RA) patients and to evaluate generalizability over gender, age, and disease duration. A sample of 682 patients was drawn from the DREAM registry. Agreement between the two DAS28 scores was analyzed using the intraclass correlation coefficient (ICC), Bland Altman plots, and a matrix of classification agreement over DAS28 disease activity categories. Despite a strong linear correlation between the DAS28 scores and a high ICC value of 0.931, a considerable lack of individual agreement could be observed, with Bland-Altman 95 % limits of agreement ranging between -0.85 and +1.25 points. On average, DAS28-CRP scores were 0.20 points lower than DAS28-ESR scores, and data stratification on age and gender showed that this systematic bias was most severe in older women (0.39 points). The overall classification agreement across DAS28 categories was 76.69 %, with the agreement being lowest (35.37 %) in the low disease activity group. Patients were more easily classified as being in remission when using the DAS28-CRP measure. DAS28-ESR and DAS28-CRP scores are not interchangeable within individuals. The DAS28-CRP tends to yield lower values of disease activity than the DAS28-ESR, resulting in substantial classification differences

Comparison of internal and external responsiveness of the generic Medical Outcome Study Short Form-36 (SF-36) with disease-specific measures in rheumatoid arthritis

OBJECTIVE: To examine the comparative internal and external responsiveness of the generic Medical Outcome Study Short Form-36 Health Survey (SF-36) and disease-specific measures in patients with rheumatoid arthritis (RA).\ud METHODS: Data were collected from 280 RA patients starting anti-tumor necrosis factor treatment. A total of 168 patients completed a questionnaire including the SF-36, the Arthritis Impact Measurement Scales 2 (AIMS2), the Health Assessment Questionnaire (HAQ), a visual analog scale for general health (VAS-GH), and an 11-point numerical rating scale for pain (NRS pain) at baseline and after 12 months. Internal responsiveness was evaluated with paired samples t-tests and standardized response means (SRM). External responsiveness was investigated with receiver-operating characteristic statistics and Spearman rank-order correlation coefficients. A health transition item was used as the external indicator of change.\ud RESULTS: No significant differences in internal and external responsiveness were found between the SF-36 and disease-specific measures within the domains physical function, pain, and psychological function. In the domain social function, the SF-36 was more responsive than the AIMS2. In the domain general health, the SF-36 was less responsive (only internal) than the AIMS2 and VAS-GH.\ud CONCLUSION: Our study showed comparable internal and external responsiveness of the SF-36 compared with disease-specific measures (AIMS2, HAQ, NRS pain) in all health domains, except social function and general health domains. The assumption that disease-specific measures are more responsive to detect intervention-related changes over time is not confirmed by our data