A Practical Approach to the Use of Conventional Synthetic, Biologic and Targeted Synthetic Disease Modifying Anti-Rheumatic Drugs for the Treatment of Inflammatory Arthritis in Patients with a History of Malignancy.

PURPOSE OF REVIEW: Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) have been used in the treatment of inflammatory arthritis (IA) for many years. More recently, biologic (bDMARDs) and targeted synthetic (tsDMARDs) DMARDs have further improved treatment. Due to increased patient longevity and effective oncology treatment, rheumatologists often encounter patients with IA and previous malignancy. The immunosuppressive effect of DMARDs causes concern regarding impaired tumour surveillance with a potential increased risk of malignancy. We reviewed the literature regarding the risk of malignancy in patients on cs-/b-/tsDMARDS and sought to provide practical advice regarding use of these drugs in patients with previous malignancy. RECENT FINDINGS: Data from randomised controlled trials is limited as patients with pre-existing malignancy are often excluded. Reassuringly, an increasing range of "real world" data from various national b/tsDMARD registries has not provided a convincing signal that these drugs increase tumour recurrence. Nevertheless, awareness of, and adherence to, national screening guidelines for malignancy is important. Given the improvement in quality of life achieved with these novel and well-tolerated therapeutic agents, the benefit/risk profile remains overwhelmingly favourable in most patients.

A practical approach to vaccination of patients with autoimmune inflammatory rheumatic diseases in Australia.

Autoimmune inflammatory rheumatic diseases (AIIRD), such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis are often complicated by infection, which results in significant morbidity and mortality. The increased risk of infection is probably due to a combination of immunosuppressive effects of the AIIRD, comorbidities and the use of immunosuppressive conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and more recently, targeted synthetic DMARDs and biologic DMARDs that block specific pro-inflammatory enzymes, cytokines or cell types. The use of these various DMARDs has revolutionised the treatment of AIIRD. This has led to a marked improvement in quality of life for AIIRD patients, who often now travel for prolonged periods. Many infections are preventable with vaccination. However, as protective immune responses induced by vaccination may be impaired by immunosuppression, where possible, vaccination may need to be performed prior to initiation of immunosuppression. Vaccination status should also be reviewed when planning overseas travel. Limited data regarding vaccine efficacy in patients with AIIRD make prescriptive guidelines difficult. However, a vaccination history should be part of the initial work-up in all AIIRD patients. Those caring for AIIRD patients should regularly consider vaccination to prevent infection within the practicalities of routine clinical practice.

Improving osteoporosis management following minimal trauma fracture in a regional setting: The Coffs Fracture Card Project.

OBJECTIVES: To improve osteoporosis (OSP) management following minimal trauma fracture (MTF) with few additional resources. DESIGN: Population intervention with serial cross-sectional analysis. SETTING: Regional setting involving primary care, base hospital and private hospital. PARTICIPANTS: Patients with MTF. INTERVENTION: A 'Fracture Card' prompting OSP management was provided to all patients post-MTF. Patients were encouraged to attend their general practitioner (GP) with this to discuss bone health issues. The 2-year intervention was supported by a public health education campaign. MAIN OUTCOME MEASURES: Number of (i) serum 25-OH vitamin D assays, (ii) dual-energy X-ray absorptiometry (DXA) scans, and (iii) new Pharmaceutical Benefits Scheme (PBS)-subsidised prescriptions for bone protective therapy (bisphosphonates, raloxifene, strontium, teriparatide, denosumab). RESULTS: The number of serum 25-OH vitamin D assays ordered in Coffs Harbour increased from 329 ± 15 per month (July 2009-June 2010) to 568 ± 21 (July 2010-June 2012; P < 0.001). The number of DXA scans performed per month increased from 192 ± 14 (July 2009-June 2010) to 296 ± 12 (July 2010-June 2012; P < 0.001). There was no difference in the number of new PBS-subsidised prescriptions for bone protective therapy in the Coffs statistical subdivision over that time (176 ± 3.8 per month, July 2009-June 2010 versus 180 ± 3.5, July 2010-June 2012, P > 0.05). CONCLUSIONS: The intervention was associated with an increased number of 25-OH vitamin D assays and DXA scans but not with more prescriptions for bone protective therapy. This suggests that a public health education campaign and provision of a 'prompt' for GPs was only partially successful at improving OSP management post-MTF. This has driven establishment of a Fracture Liaison Service.

The initial 18 months of the first multi-disciplinary regional Pulmonary Arterial Hypertension Clinic in Australia.

OBJECTIVE: To report the initial 18 months experience of the first multi-disciplinary regional Pulmonary Arterial Hypertension (PAH) Clinic in Australia. DESIGN: Prospective cohort study. SETTING: Community setting on the mid-north coast of New South Wales. PARTICIPANTS: A total of 47 patients (mean age±standard error of the mean: 71.8±1.8 years; male/female ratio 13/34). MAIN OUTCOME MEASURES: Diagnosis of PAH, exclusion of other causes of pulmonary hypertension, commencement of PAH-specific pharmacotherapy. RESULTS: Twenty-three (49%) patients were discharged back to their GP with pulmonary hypertension from a combination of ischaemic heart and/or lung disease. Three (6%) patients died from connective tissue disease (CTD)-related PAH with one death (2%) from ischaemic heart disease. Five (11%) patients remain on treatment (n=2, Bosentan for congenital heart disease-related PAH; n=1 Bosentan for CTD-related PAH; and n=1 Bosentan and n=1 Sildenafil for primary PAH). Fifteen (32%) patients have ongoing review for PAH related to CTD (n=11), carcinoid (n=1) and uncertain cause (n=3). CONCLUSION: Patients with CTD-related PAH have a poor prognosis. PAH should be considered in anyone with dyspnoea without obvious features of cardiac or pulmonary disease, especially in the setting of a CTD. Regional population centres are under-resourced with PAH specialty medical services. We have sought to address this by establishment of the first regional multi-disciplinary PAH Clinic in Australia.

Assessing the readability and patient comprehension of rheumatology medicine information sheets: a cross-sectional Health Literacy Study.

OBJECTIVES: Patients are often provided with medicine information sheets (MIS). However, up to 60% of patients have low health literacy. The recommended readability level for health-related information is ≤grade 8. We sought to assess the readability of MIS given to patients by rheumatologists in Australia, the UK and Canada and to examine Australian patient comprehension of these documents. DESIGN: Cross-sectional study. SETTING: Community-based regional rheumatology practice. PARTICIPANTS: Random sample of patients attending the rheumatology practice. OUTCOME MEASURES: Readability of MIS was assessed using readability formulae (Flesch Reading Ease formula, Simple Measure of Gobbledygook scale, FORCAST (named after the authors FORd, CAylor, STicht) and the Gunning Fog scale). Literal comprehension was assessed by asking patients to read various Australian MIS and immediately answer five simple multiple choice questions about the MIS. RESULTS: The mean (±SD) grade level for the MIS from Australia, the UK and Canada was 11.6±0.1, 11.8±0.1 and 9.7±0.1 respectively. The Flesch Reading Ease score for the Australian (50.8±0.6) and UK (48.5±1.5) MIS classified the documents as 'fairly difficult' to 'difficult'. The Canadian MIS (66.1±1.0) were classified as 'standard'. The five questions assessing comprehension were correctly answered by 9/21 patients for the adalimumab MIS, 7/11 for the methotrexate MIS, 6/28 for the non-steroidal anti-inflammatory MIS, 10/11 for the prednisone MIS and 13/24 for the abatacept MIS. CONCLUSIONS: The readability of MIS used by rheumatologists in Australia, the UK and Canada exceeds grade 8 level. This may explain why patient literal comprehension of these documents may be poor. Simpler, shorter MIS with pictures and infographics may improve patient comprehension. This may lead to improved medication adherence and better health outcomes.

Pilot study assessing the novel use of musculoskeletal ultrasound in patients with rheumatoid arthritis to improve patient attitudes and adherence to medication.

OBJECTIVE: To determine if showing patients with rheumatoid arthritis (RA) ultrasound (US) images of their inflamed joints: (i) increased belief in the necessity of medication; (ii) encouraged patient activation, that is, confidence and understanding in managing their health; and (iii) facilitated medication adherence. METHOD: Eighteen patients aged ≥ 18 years old with active RA (DAS28 [Disease Activity Score of 28 joints] > 2.6) requiring increased immunosuppression were included. The following questionnaires were administered at baseline (T1), 3 days post-US (T2) and 10 days post-US (T3): (i) Beliefs about Medicines Questionnaire (BMQ) to measure the cost-benefit analysis made by patients regarding the necessity versus concern of medication; (ii) Patient Activation Measure (PAM-13) to assess patient activation; (iii) Compliance Questionnaire-Rheumatology (CQR) to measure medication adherence; and (iv) Routine Assessment of Patient Index-3 (RAPID3) to assess physical function, pain and global status. US of ≥ 1 clinically affected joints was performed on one occasion with an explanation of findings. RESULTS: Patient cost-benefit decisions shifted positively following US, that is, favored belief in the necessity of medication with a mean ± SD cost-benefit ratio (possible range - 20 to + 20) at T1 of 1.17 ± 6.10 which increased to 2.54 ± 5.38 at T2 and 4.06 ± 5.76 at T3, P = 0.043 by analysis of variance (anova). PAM-13, CQR and RAPID3 scores remained stable (all P > 0.05 by anova). CONCLUSION: Showing patients with RA 'real-time' US images of clinically inflamed joints resulted in a more favorable cost-benefit analysis, that is, increased patient belief in the necessity of medication versus concern about taking medication. There was no change in patient activation, medication adherence or disease severity.

How well do patients understand written instructions?: health literacy assessment in rural and urban rheumatology outpatients.

The aim of this study was to assess health literacy (word recognition and comprehension) in patients at a rural rheumatology practice and to compare this to health literacy levels in patients from an urban rheumatology practice.Inclusion criteria for this cross-sectional study were as follows: ≥18-year-old patients at a rural rheumatology practice (Mid-North Coast Arthritis Clinic, Coffs Harbour, Australia) and an urban Sydney rheumatology practice (Combined Rheumatology Practice, Kogarah, Australia). Exclusion criteria were as follows: ill-health precluding participation; poor vision/hearing, non-English primary language. Word recognition was assessed using the Rapid Estimate of Adult Literacy in Medicine (REALM). Comprehension was assessed using the Test of Functional Health Literacy in Adults (TOFHLA). Practical comprehension and numeracy were assessed by asking patients to follow prescribing instructions for 5 common rheumatology medications.At the rural practice (Mid-North Coast Arthritis Clinic), 124/160 patients agreed to participate (F:M 83:41, mean age 60.3 ±â€Š12.2) whereas the corresponding number at the urban practice (Combined Rheumatology Practice) was 99/119 (F:M 69:30, mean age 60.7 ±â€Š17.5). Urban patients were more likely to be born overseas, speak another language at home, and be employed. There was no difference in REALM or TOFHLA scores between the 2 sites, and so data were pooled. REALM scores indicated 15% (33/223) of patients had a reading level ≤Grade 8 whereas 8% (18/223) had marginal or inadequate functional health literacy as assessed by the TOFHLA. Dosing instructions for ibuprofen and methotrexate were incorrectly understood by 32% (72/223) and 21% (46/223) of patients, respectively.Up to 15% of rural and urban patients had low health literacy and <1/3 of patients incorrectly followed dosing instructions for common rheumatology drugs.There was no significant difference in word recognition, functional health literacy, and numeracy between rural and urban rheumatology patients.

Measures of rheumatoid arthritis disease activity in Australian clinical practice.

Objectives. To investigate which rheumatoid arthritis (RA) disease activity measures are being collected in patients receiving glucocorticoids, non-biologic or biologic disease-modifying antirheumatic drugs (DMARDs) in Australian rheumatology practice. Methods. A retrospective audit of medical records was conducted from eight rheumatology practices around Australia. Each rheumatologist recruited 30 consecutive eligible patients into the review, 10 of whom must have been receiving a biological agent for rheumatoid arthritis. Disease activity measures and radiographic assessments were collected from each patient's last consultation. For biologic patients, disease activity measures were also collected from when the patient was first initiated on the biological agent. Results. At last consultation, the disease measures that were recorded most often were ESR (89.2%), haemoglobin (87.5%), and CRP (84.2%). DAS28 was infrequently recorded (16.3%). The rate of recording disease activity measures for patients receiving biologic DMARDs decreased over time (mean 27 months). Conclusion. This review has shown inconsistency of RA activity measures being recorded in Australian rheumatology clinical practice. An accurate assessment of the disease process is necessary to effectively target rheumatoid arthritis patients to treat in order to achieve optimal outcomes.

Predictors of clinical response to intraarticular Hylan injections -- a prospective study using synovial fluid measures, clinical outcomes, and magnetic resonance imaging.

OBJECTIVE: To evaluate synovial fluid (SF) and clinical and imaging predictors of clinical response in patients receiving intraarticular Hylan GF-20 injections. METHODS: Thirty-two patients with mild to moderate osteoarthritis (OA) of the knee [OsteoArthritis Research Society International (OARSI) grades I-II] were followed over 6 months. SF and clinical and radiographic measures were assessed. Patella and tibial cartilage volume and cartilage defect scores were measured at baseline and 6 months using magnetic resonance imaging (MRI). The primary outcome measure was the relationship between SF measures and clinical response as defined by the OARSI-Outcome Measures in Rheumatology Clinical Trials responder criteria for OA ("High improvement" >or= 50% improvement in pain or function; absolute change >or= 20 NU on Western Ontario and McMaster University Osteoarthritis Index questionnaire). Secondary outcomes included MRI outcomes (change in cartilage volume and cartilage defect scores). RESULTS: Fifteen patients achieved "High improvement." High baseline SF hyaluronic acid (HA) concentration was a statistically significant predictor of clinical response with odds ratio (OR) 6.04 (p < 0.02). HA concentration was divided into tertiles and fitted to a univariate regression model against clinical response. A baseline HA concentration value of > 2 mg/ml provided the greatest tradeoff between sensitivity and specificity with values of 60% and 77%, respectively, a likelihood ratio of 2.55, and OR of 4.88. Baseline clinical and radiological measures did not predict clinical response in this cohort with mild to moderate OA. Nineteen subjects had MRI at both timepoints. No change was noted in cartilage volumes or cartilage defect scores over 6 months. There was no association between baseline HA concentration and baseline cartilage volume. CONCLUSION: Baseline SF HA concentration predicts clinical response in patients receiving intraarticular Hylan. This has implications for the selection of patients who are likely to respond to this therapy.

Longterm effects of intraarticular hyaluronan on synovial fluid in osteoarthritis of the knee.

OBJECTIVE: Intraarticular (IA) hylan injections constitute second-line therapy for osteoarthritis (OA) of the knee, but human studies suggesting a possible mechanism of action are lacking. We examined the effect of IA Hylan GF-20 injections on synovial fluid (SF) hyaluronan (HA) concentration, viscosity, and elasticity over a 6-month period in patients with mild to moderate OA of the knees. METHODS: Patients with symptomatic knee OA (Osteoarthritis Research Society International grade 1-2) had SF aspirated from the study knee pre- and 3 and 6 months post-Hylan injection. Primary endpoints included SF HA concentration, viscosity, and elasticity. SF HA concentration was determined using uronic acid assay, and rheology measured using a micro-Fourier rheometer. RESULTS: Sequential SF samples were available from 32 of 60 subjects injected at baseline (15 men, 17 women; mean age 65 yrs) at 3 months post-injection. The mean HA concentration had increased by 13% (p<0.0008), and the complex shear modulus had increased by 16% (p<0.03). Sufficient SF was also available from 19 of these subjects at 6 months post-injection when mean HA concentration was 2.24+/-0.62 mg/ml compared to their baseline mean of 2.02+/-0.52 mg/ml, an increase of 10% (p<0.053). CONCLUSION: This open-label study showed a statistically significant change from baseline in both SF HA concentration and complex shear modulus at 3 months following IA Hylan GF-20 injection among subjects with mild to moderate knee OA. These results suggest that one possible mechanism of action of viscosupplementation is to promote endogenous HA production. Longer-term studies are required to identify whether these changes in SF measures are important for modification of disease progression in knee OA.

Epidemiology of osteoarthritis in Australia.

Arthritis affects around 3 million people in Australia, representing about 15% of the population. Osteoarthritis is the leading cause of pain and disability among the elderly. Osteoarthritis is the third leading cause of life-years lost due to disability. Obesity and joint injury are important potentially modifiable risk factors for the development of osteoarthritis. Obesity is also an important predictor of progression of osteoarthritis. Currently, about 19000 hip and 20000 knee replacements are performed for osteoarthritis in Australia each year. Prevalence of osteoarthritis and the need for total joint replacement surgery are likely to increase because of a combination of increasing risk factors (age, obesity, injury), increasing expectations for improved quality of life, and improved surgical and anaesthetic techniques making surgery possible for more people. Services to provide these cost-effective procedures need to be increased. Primary and secondary prevention programs aimed at reducing obesity, preventing injury and improving rehabilitation and physical activity are urgently required.