The CEDAR Study: A longitudinal study of the clinical effects of conventional DMARDs and biologic DMARDs in Australian rheumatology practice

Objectives. To observe the choices of conventional disease modifying antirheumatic drugs (cDMARDs) and biologic DMARDs (bDMARDs) in the management of rheumatoid arthritis (RA) in Australian routine clinical practice, to assess treatment survival and determine the effect of cDMARDs/bDMARDs on disease activity. Methods. Routinely collected, deidentified clinical data was sourced from 20 Australian rheumatology practices. RA patients aged ≥18 years, who had received cDMARDs/bDMARDs and a recorded subsequent visit, were included. A linear mixed model was used to determine the change over time and the percentage reduction in disease activity was summarized. Results. 12,526 RA patients were included: 72% females, mean age 62 years. cDMARDs and bDMARDs were used in 92% and 30% of patients, respectively. The most commonly prescribed cDMARD was methotrexate (76% patients); median time to stopping treatment was 337 months [95% CI: 279–ND]. Etanercept was the most commonly prescribed bDMARD (12% patients); median time to stopping treatment was 79 months [95% CI: 57–93]. Of 5,341 patients with a first change in medication (cDMARD or bDMARD), 87% had therapy escalation and 13% deescalation. Reduction in DAS28-ESR, 6-month post-DMARDs initiation ranged from 3%, adalimumab, to 14%, leflunomide and tocilizumab. Conclusions. In this large Australian cohort of unselected community RA patients, the choices of cDMARDs/bDMARDs are aligned with current international guidelinesThis work was supported by Roche Products Pty Limited (Australia)

The CEDAR Study: A Longitudinal Study of the Clinical Effects of Conventional DMARDs and Biologic DMARDs in Australian Rheumatology Practice

Objectives. To observe the choices of conventional disease modifying antirheumatic drugs (cDMARDs) and biologic DMARDs (bDMARDs) in the management of rheumatoid arthritis (RA) in Australian routine clinical practice, to assess treatment survival and determine the effect of cDMARDs/bDMARDs on disease activity. Methods. Routinely collected, deidentified clinical data was sourced from 20 Australian rheumatology practices. RA patients aged ≥18 years, who had received cDMARDs/bDMARDs and a recorded subsequent visit, were included. A linear mixed model was used to determine the change over time and the percentage reduction in disease activity was summarized. Results. 12,526 RA patients were included: 72% females, mean age 62 years. cDMARDs and bDMARDs were used in 92% and 30% of patients, respectively. The most commonly prescribed cDMARD was methotrexate (76% patients); median time to stopping treatment was 337 months [95% CI: 279–ND]. Etanercept was the most commonly prescribed bDMARD (12% patients); median time to stopping treatment was 79 months [95% CI: 57–93]. Of 5,341 patients with a first change in medication (cDMARD or bDMARD), 87% had therapy escalation and 13% deescalation. Reduction in DAS28-ESR, 6-month post-DMARDs initiation ranged from 3%, adalimumab, to 14%, leflunomide and tocilizumab. Conclusions. In this large Australian cohort of unselected community RA patients, the choices of cDMARDs/bDMARDs are aligned with current international guidelines

Methylation profiling RIN3 and MEF2C identifies epigenetic marks associated with sporadic early onset Alzheimer’s disease

A number of genetic loci associate with early onset Alzheimer’s disease (EOAD), however the drivers of this disease remains enigmatic. Genome wide association and in-vivo modelling have shown that loss-of-function e.g. ABCA7, reduced levels of SIRT1, MEFF2C or increases levels of PTK2β confer risk or link to the pathogenies. It is known that DNA methylation can profoundly affect gene expression and can impact on the composition of the proteome, therefore the aim of this study is to assess if genes associated with sporadic EOAD are differentially methylated. Epi-profiles of DNA extracted from blood and cortex were compared using a pyrosequencing platform. We identified significant group-wide hypomethylation in AD blood when compared to controls for 7 CpGs located within the 3’UTR of RIN3 (CpG1 P=0.019, CpG2 p=0.018, CpG3 p=0.012, CpG4 p=0.009, CpG5 p=0.002, CpG6 p=0.018 and CpG7 p=0.013 respectively; AD / Control n=22 / 26; Male / Female, 27 / 21). Observed effects were not gender specific. No group wide significant differences were found in the promoter methylation of PTK2β, ABCA7, SIRT1 or MEF2C, genes known to associate with LOAD. A rare and significant difference in methylation was observed for one CpG located upstream of the MEF2C promoter in one AD individual only (22% reduction in methylation, p=2.0E-10; Control n=26, AD n=25, Male / Female n=29 / 22). It is plausible aberrant methylation may mark sEOAD in blood and may manifest in some individuals as rare epi-variants for genes linked to sEOAD

Peripheral blood biomarkers in multiple sclerosis.

Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heteroge-neity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpre-dictable response to therapies. The major focus of the research on MS is the identification of biomarkers inbiologicalfluids, such as cerebrospinalfluid or blood, to guide patient management reliably. Because of the diffi-culties in obtaining spinalfluid samples and the necessity for lumbar puncture to make a diagnosis has reduced,the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However,currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkerscould radically alter the management of MS at critical phases of the disease spectrum, allowing for interventionstrategies that may prevent evolution to long-term neurological disability. This article provides an overview ofthis researchfield and focuses on recent advances in blood-based biomarker researc

Patients with rheumatoid arthritis in the Australian OPAL cohort show significant improvement in disease activity over 5 Years: a multicenter observational study

Objective: To evaluate disease activity trends in a large cohort of Australian patients with rheumatoid arthritis (RA) from 2009 to 2014. Methods: This is a multicenter, cross-sectional, noninterventional study of patients with RA treated in Australia. Patients with RA treated at participating OPAL (Optimising Patient outcome in Australian RheumatoLogy) clinics were included in the study. Data, deidentified by patient, clinic, and clinician, were identified using a purpose-written electronic medical record. Patient demographics, disease onset, medications, and disease measures were analyzed. The Disease Activity Score at 28 joints (DAS28) was used to classify patients into the disease activity states of remission: low disease activity, moderate disease activity (MDA), and high disease activity. Choice of therapy was at the discretion of the treating clinician. Results: At the time of analysis, the database contained 15,679 patients with RA, 8998 of whom fulfilled the inclusion criteria. Mean age was 63.2 years, mean disease duration was 13.8 years, and the majority were women (72.4%). A total of 37,274 individual DAS28-erythrocyte sedimentation rate scores were recorded for the 8998 patients. The frequency of remission increased significantly from 36.7% in 2009 to 53.5% in 2014 (p < 0.001), and that of MDA decreased from 33% (2009) to 22.2% (2014). The use of biologic disease-modifying antirheumatic drugs for the patients in remission increased from 17% in 2009 to 36.9% in 2014. Conclusion: Contemporary management of RA in Australia shows improvements in disease activity toward the target of remission over a 5-year period

Longitudinal study of clinical prognostic factors in patients with early rheumatoid arthritis: the PREDICT study

Aim: To assess the association between baseline clinical prognostic factors and subsequent Disease Activity Scoreof 28 joints (DAS28) remission in early rheumatoid arthritis (RA).Methods: Data were collected using point of care clinical software from participating rheumatology centres.Patients aged 18 years or over whose date of clinical onset of RA was within the previous 12–24 months, whohad at least 6 months of follow-up data and a DAS28-ESR (erythrocyte sedimentation rate) score recordedbetween 12 and 24 months from first being seen for RA were included. Data collected included baseline demo-graphics, mode of disease onset, pattern of joint involvement at onset, smoking status, DAS28, rheumatoid fac-tor (RF), anti-citrullinated peptide antibodies (ACPA), time from symptom onset to presentation and diseaseactivity at baseline. Univariate and multivariate logistic regression of DAS28-ESR remission between 12 and24 months after first assessment were performed.Results: Data from 1017 patients were analyzed: 70% female; mean age 60 years (SD: 14.7); 70% RF-positive,58% ACPA-positive. The strongest age and sex adjusted baseline predictors of DAS28-ESR remission at 12–24 months were remission at baseline (odds ratio [OR]: 4.49, 95% CI: 2.17 –9.29, P < 0.001), being male (OR:2.42, 95% CI: 1.46 –4.01, P < 0.001), abstaining from alcohol (P < 0.001) and being lower weight (OR: 0.98,95% CI: 0.97–1.00, P = 0.015). There was no statistically significant association between joint onset patterns,mode of onset, RF, ACPA or smoking status.Conclusion: In this observational study, patients with early RA at risk of not achieving remission include thosewith high disease activity at baseline, women, those who drink alcohol and those with higher body weight.The study was supported by Roche Products Pty Ltd (Australia)