Using big data from real-world Australian rheumatology encounters to enhance clinical care and research.

OBJECTIVES: OPAL (Optimising Patient outcomes in Australian rheumatoLogy) Rheumatology is an independent not for profit Australian clinical research organisation which is the custodian of one of the largest datasets of patients with rheumatic diseases in the world, containing real-world clinical data from more than >175,000 unique patients collected over more than 900,000 clinical consultations. We describe the evolution and outcomes of the OPAL dataset, with particular reference to the use of big data derived from real-world clinical encounters to enhance clinical care and research. METHODS: De-identified data are regularly extracted and aggregated from the electronic medical records (EMR) of consenting patients treated by approximately 100 rheumatologists around Australia. The EMR shared by OPAL clinicians was specifically customised for rheumatology and collects comprehensive information on demographics, disease history, activity and severity, co-morbidities, pathology, and medication use. In addition, OPAL captures multifaceted outcomes data from the patient perspective through a novel electronic patient-reported outcome (ePRO) delivery system which allows for health-related quality of life measures to be matched with clinical indices. RESULTS: Since inception in 2009, OPAL has produced 35 publications and abstracts. OPAL also provides real-world data to determine drug utilisation, efficacy and safety, elucidate the natural history of disease, highlight areas of unmet need, guide medical affairs and commercial strategy, and to support regulatory and reimbursement submissions. CONCLUSIONS: The extensive, evolving and organic OPAL dataset reflects the complexities of clinical rheumatological practice. It provides unique opportunities to enhance clinical care and research.

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.

A multi-center, observational study shows high proportion of Australian rheumatoid arthritis patients have inadequate disease control.

OBJECTIVES: To evaluate the disease activity and current pharmacological interventions used to achieve remission in rheumatoid arthritis (RA) patients in Australia. METHODS: Rheumatoid arthritis patients treated in participating Australian clinics were included in the study. Patient demographics, disease onset, medications and disease measures were analyzed. Data, de-identified to the patient, clinic and clinician were captured using an electronic clinical management program. The disease activity score (DAS28) was used to classify patients into the disease activity states of remission, low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA). Choice of therapy was at the discretion of the treating clinician. RESULTS: A total of 5686 patients, 72.9% female, 26.9% male, with mean age 61.1 (SD 13.6) years and mean disease duration of 11.5 (SD 10.5) years were analyzed. DAS28 ESR (erythrocyte sedimentation rate) scores were recorded for 2973 patients, with 41.6% in remission, 18.6% LDA, 31.6% MDA and 8.2% HDA. Of those in remission, 17% received a biological disease modifying anti-rheumatic drug (bDMARD), 73% methotrexate (MTX), 19% leflunomide (LEF) and 28% prednisolone. Of the patients with MDA, 20% received a bDMARD, 76% MTX, 24% LEF and 39% prednisolone. Of the patients in HDA, 27% received a bDMARD, 78% MTX, 31% LEF and 60% with prednisolone. CONCLUSIONS: Cross-sectional assessment of this large cohort of Australian RA patients found a large proportion remain in moderate or high disease activity; suggesting a considerable evidence-practice gap. Improvement in disease control in this group may reduce future health burdens.

Dramatic regulation of heparanase activity and angiogenesis gene expression in synovium from patients with rheumatoid arthritis.

OBJECTIVE: Although heparanase is recognized as a proangiogenic factor, the involvement of heparanase in rheumatoid arthritis (RA) is unclear. In this study, we assessed heparanase activity in synovial fluid (SF) and synovial tissue (ST) from patients with RA or osteoarthritis (OA), and analyzed the expression of angiogenic pathway-focused genes in ST from RA and OA patients. METHODS: SF and ST were obtained from the knees of patients with either RA or OA and from asymptomatic donors with no documented history of degenerative or inflammatory joint diseases. Heparanase activity was determined by an enzymatic assay using a radiolabeled substrate, and the presence of heparanase in ST was demonstrated by Western blotting. The expression of angiogenesis genes, including heparanase, in ST was analyzed by real-time quantitative polymerase chain reaction. RESULTS: Heparanase activity was dramatically higher (>100-fold) in SF and ST from RA patients than in SF and ST from OA patients and asymptomatic donors. Active heparanase enzyme was detected and heparanase messenger RNA was up-regulated in ST from RA patients. We also found that angiogenesis gene expression was significantly regulated in RA synovium, and was correlated with heparanase activity. CONCLUSION: These findings are novel and contribute to our understanding of joint destruction in RA, suggesting that heparanase may be a reliable prognostic factor for RA progression and an attractive target for the treatment of RA.

Methotrexate in the management of granulomatous mastitis.

Granulomatous mastitis is a rare benign inflammatory breast disease that often clinically simulates carcinoma. Surgical resection of the entire lesion has been the main method of treatment but recurrence, infection, sinus formation and delayed wound healing can occur relatively commonly. Corticosteroids are also effective in recurrent or resistant cases but are associated with side-effects and relapse of disease after steroid withdrawal. A low weekly oral dose of methotrexate was used in five resistant cases after surgery plus corticosteroid. All cases achieved remission, withdrawal of corticosteroid without relapse and no methotrexate side-effect.