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Objectives To determine long-term (20 year) survival in RA patients enrolled in the Australian Rheumatology Association Database (ARAD). Methods ARAD patients with RA and data linkage consent who were diagnosed from 1995 onwards were included. Death data were obtained through linkage to the Australian National Death Index. Results were compared with age-, gender- and calendar year–matched Australian population mortality rates. Analysis included both the standardized mortality ratio (SMR) and relative survival models. Restricted mean survival time (RMST) at 20 years was calculated as a measure of life lost. Cause-specific SMRs (CS-SMRs) were estimated for International Classification of Diseases, Tenth Revision cause of death classifications. Results A total of 1895 RA patients were included; 74% were female, baseline median age 50 years (interquartile range 41–58), with 204 deaths. There was no increase in mortality over the first 10 years of follow up, but at 20 years the SMR was 1.49 (95% CI 1.30, 1.71) and the relative survival was 94% (95% CI 91, 97). The difference between observed (18.41 years) and expected (18.68 years) RMST was 4 months. Respiratory conditions were an important underlying cause of death in RA, primarily attributable to pneumonia [CS-SMR 5.2 (95% CI 2.3, 10.3)] and interstitial lung disease [CS-SMR 7.6 (95% CI 3.0, 14.7)], however, coronary heart disease [CS-SMR 0.82 (95% CI 0.42, 1.4)] and neoplasms [CS-SMR 1.2 (95% CI 0.89, 1.5)] were not. Conclusion Mortality risk in this RA cohort accrues over time and is moderately increased at 20 years of follow-up. Respiratory diseases may have supplanted cardiovascular diseases as a major contributor to this mortality gap.

To examine the relationship between corticosteroid use and herpes zoster risk.With data from a large cohort of adults (the 45 and Up Study) recruited between 2006 and 2009 and linked to health data sets, the effect of corticosteroid use on zoster risk was analyzed by Cox proportional hazards models, adjusting for age, sex, and other characteristics.During 602,152 person-years (median, 7.36 years) of follow-up, there were 20,048 new systemic corticosteroid users and 6294 incident herpes zoster events among 94,677 participants (zoster incidence, 11.0 per 1000 person-years). Compared with nonusers, the risk of zoster was 59% higher in those using systemic corticosteroids (adjusted hazard ratio [aHR], 1.59; 95% CI, 1.48 to 1.71) and greater with higher cumulative doses: aHR of 1.32 (95% CI, 1.17 to 1.48), 1.74 (95% CI, 1.55 to 1.95), and 1.80 (95% CI, 1.61 to 2.02) for use of less than 500 mg, 500 mg to less than 1000 mg, and 1000 mg or more prednisolone equivalents, respectively (P value for trend,.001). Compared with nonusers, zoster risk increased significantly (aHR, 6.00; 95% CI, 4.85 to 7.42) in the month after a single prescription of systemic corticosteroids and returned to levels similar to those in nonusers by the third month after dispensing (aHR, 0.91; 95% CI, 0.49 to 1.69).Practitioners should be alert to the increased risk of zoster among patients taking systemic corticosteroids. Given the significant morbidity from zoster, particularly in older adults, these findings support judicious prescribing of corticosteroids, including using as low a dose and as short a course as possible.

Objectives To examine the association between DMARD use and subsequent risk of herpes zoster in a large, heterogeneous and prospective population-based cohort. Methods Using data from a cohort of adults (45 and Up Study) recruited between 2006 and 2009 and linked to pharmaceutical, hospital and death data (2004–2015), the effect of DMARD use on zoster risk was analysed using Cox proportional hazards models, adjusting for sociodemographic characteristics, comorbidities and corticosteroid use. Results Among 254 065 eligible participants, over 1 826 311 person-years follow-up, there were 6295 new DMARD users and 17 024 incident herpes zoster events. Compared with non-users, the risk of zoster was higher in those who used biologic (b)DMARDs, either alone or in combination with conventional synthetic (cs)DMARDs than in those who only used csDMARDs (adjusted hazard ratio [aHR] 2.53 [95% CI: 2.03, 3.16]) for bDMARDs vs 1.48 [95% CI: 1.33, 1.66] for csDMARDs, P-heterogeneity Conclusions The risk of zoster was high among bDMARD and cyclophosphamide users. Also, the risk was increased in those using hydroxychloroquine alone and in combination with methotrexate but not methotrexate alone. Preventative strategies such as zoster vaccination or antiviral therapies should be considered in these populations if not contraindicated.

Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms).

Objective The aim of this study was to describe treatment patterns in RA, including the frequency and reasons for switching or stopping biologic and targeted synthetic DMARDs (b/tsDMARDs). Methods The reasons for switching or stopping b/tsDMARDs were extracted from the Australian Rheumatology Association Database (ARAD) from 2003 to 2018 for RA participants. Switching patterns for each b/tsDMARD and time on first-, second- and third-line b/tsDMARDs were evaluated using Sankey diagrams and survival methods. Results A total of 2839 participants were included in the analysis. The first-line b/tsDMARDs were etanercept (n = 1414), adalimumab (n = 1024), infliximab (n = 155), golimumab (n = 98), abatacept (n = 66), certolizumab (n = 38), tocilizumab (n = 21) and tofacitinib (n = 23). Of those starting first-, second- and third-line biologic therapy, 24.0%, 31.8% and 24.4% switched to another b/tsDMARD within 12 months, respectively. Inefficacy or adverse effects were the most common reasons for stopping therapy, irrespective of line of treatment. Compared with first-line etanercept, participants were more likely to stop adalimumab [Hazard ratio (HR) 1.16, 95% CI: 1.04, 1.29] and infliximab (HR 1.77, 95% CI: 1.46, 2.16). No differences were seen for other b/tsDMARDs. For second-line therapies compared with etanercept, the risk of stopping was lower for tocilizumab (HR 0.41, 95% CI: 0.25, 0.70), rituximab (HR 0.51, 95% CI: 0.30, 0.85) and tofacitinib (HR 0.29, 95% CI: 0.15, 0.57). Participants taking rituximab, tocilizumab and tofacitinib were also less likely to stop third-line therapy in comparison with participants taking etanercept. Conclusions Switching between b/tsDMARDs was common among ARAD participants with RA, most commonly due to inefficacy or adverse effects. Durability of exposure and reasons for switching varied between b/tsDMARDs.

Objective.It is not known how the experience of stiffness varies between diagnoses or how best to measure stiffness. The aims of our study were to (1) compare stiffness in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) using patient-reported outcomes, (2) investigate how dimensions of stiffness are associated with each other and reflect the patient experience, and (3) analyze how different dimensions of stiffness are associated with physical function.Methods.An online survey was sent to Australian Rheumatology Association Database participants (158 PsA, and 158 age- and sex-matched RA), assessing stiffness severity, duration, impact, importance, coping, and physical function [modified Health Assessment Questionnaire (mHAQ)]. Scores were compared between diagnoses and correlations among stiffness dimensions calculated. Multivariate regression was performed for stiffness severity, impact, and duration on mHAQ, adjusting for age, sex, disease duration, obesity, and pain. Cognitive debriefing was conducted through semistructured telephone interviews.Results.Overall, 240/316 (75.9%) responded [124/158 RA (78.5%) and 116/158 PsA (73.4%)], with no significant difference in stiffness ratings between diagnoses. Scores for all stiffness dimensions were strongly correlated (r = 0.52–0.89), and severity and impact were associated with mHAQ in both diagnoses. Stiffness duration was not associated with mHAQ in RA. In cognitive debriefing, participants described stiffness severity and impact by their effect on daily activities (10/16 and 14/16 participants, respectively).Conclusion.Stiffness ratings were similar between PsA and RA. Different dimensions of stiffness were strongly correlated. Stiffness severity and impact both independently predicted mHAQ. Stiffness was important to participants; however, measuring multiple dimensions of stiffness may have minimal additive value.

Introduction: A key element in the big data revolution is large-scale biobanking and the associated development of high-quality data collections and supporting informatics solutions. As such, in establishing the Australian Arthritis and Autoimmune Biobank Collaborative (A3BC), we sought to establish a low-cost, nation-scale data management system capable of managing a multi-site biobank-registry with complex longitudinal sample and data requirements. Materials and Methods: We assessed several international commercial and non-profit software platforms using standardised system requirement criteria and follow-up interviews. Vendor compliance scoring was prioritised to meet our project-critical requirements. Consumer / end-user co-design was integral to refining our system requirements for optimised adoption. Customisation of the selected software solution was performed to optimise field auto-population between participant timepoints and forms, using modules that are transferable and do not impact core code. Institutional and independent testing was used to ensure data security. Results: We selected the widely used research web application Research Electronic Data Capture (REDCap) which is “free” (under non-profit license agreement terms), highly configurable and customisable to a variety of biobank and registry needs, and can be developed/ maintained by biobank users with modest IT skill, time and cost. We created a secure, comprehensive participant-centric biobank-registry database that includes: (a) best practice data security measures (incl. multi-site access login using institutional user credentials), (b) permission-to-contact and dynamic itemised e-consent, (c) a complete chain of custody from consent to longitudinal biospecimen-data collection to publication, (d) complex longitudinal patient-reported surveys, (e) integration of record-level extracted/ linked participant data, (f) significant form auto-population for streamlined data capture, and (g) native dashboards for operational visualisations. Conclusion: We recommend the versatile, reusable and sustainable informatics model we have developed in REDCap for prospective chronic disease biobanks or registry-biobanks (of local to national complexity) supporting holistic research into disease prediction, precision medicine and prevention strategies. Published version: Craig Willers, Tom Lynch, Vibhasha Chand, Mohammad Islam, Marissa Lassere, and Lyn March.Biopreservation and Biobanking. https://doi.org/10.1089/bio.2021.0098

AimsThe study of foundational features of meta-analysis is incomplete and continues to remain important. Using simulations we study bias and coverage and the asymptotic behaviour of the DerSimonian and Laird (D&L) meta-analysis with varying trial numbers and sizes, levels of risk, and extent of treatment effects.MethodsWith simulated data we model risk of untoward events in randomized controlled trials in meta-analyses. Treatment effect is expressed as relative risk reduction, with effect size estimated by the odds ratio which is then compared with the known population odds ratio. Performance is measured as bias, standardized bias and coverage, with thresholds for desirable results being prespecified.ResultsBias, standardized bias, and coverage varied substantially across meta-analyses of different trial size and number, risk mean and distribution, and relative risk reduction. Although improvements were observed with increasing trial size and number, there was widespread lack of satisfactory performance. Performance using normal risk distributions was worse compared with performance using constant or narrow uniform risk distributions. Asymptotic behaviour using very large trial numbers failed to show bias that appeared to approach zero for any distribution.ConclusionThe D&L random effects meta-analysis method performed modestly at best. We were unable to demonstrate asymptotic normality. These results question the validity of the random effects method. The findings need replication and extension, which, if confirmed, would warn against generic use of the D&L method.

Objectives. To describe oral complementary medicine (CM) use in people with inflammatory arthritis, associations with use, and changes in use over time. Methods. Demographic, clinical, and patient-reported outcome data from 5,630 participants with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) were extracted from the Australian Rheumatology Association Database (ARAD), a national observational database. CM use at entry into ARAD was ascertained for participants recruited between 2002 and 2018. CM was categorised according to the NIH/Cochrane schema (fatty acids, herbs, or supplements). Logistic regression was used to assess associations between demographic characteristics and CM use. Change in CM use between 2006 and 2016 was investigated using a nonparametric test for trend of rate by year. Results. 2,156 (38.3%) ARAD participants were taking CM at enrolment (RA: 1,502/3,960 (37.9%), AS: 281/736 (38.2%), PsA: 334/749 (44.6%), and JIA: 39/185 (21.1%)). CM use was more prevalent in women (OR 1.3; 95% CI: 1.13-1.50), those with tertiary education (OR 1.32; 95% CI: 1.13-1.55), private health insurance (OR 1.26; (95% CI: 1.10-1.44), drinking alcohol sometimes (OR 1.22; 95% CI: 1.05-1.43), poorer function (HAQ) (OR 1.13; 95% CI: 1.02-1.24), use of NSAID (OR 1.32; 95% CI 1.17-1.50), weak (OR 1.21; 95% CI 1.05-1.41) but not strong opioids, and less prevalent in current smokers (OR 0.76; 95%: CI 0.63-0.91). CM use was not associated with pain, disease activity, or quality of life. The most common CMs were fish oils (N=1,489 users) followed by glucosamine (N=605). Both declined in use over time between 2006 and 2016 (27.5% to 21.4%, trend p=0.85 and 15.5% to 6.4%, trend p<0.01), respectively. Conclusion. Oral CM use is common among Australians with inflammatory arthritis. Its use is greater among women and those with tertiary education. Fish oil and glucosamine, the most common CMs, both declined in use over time.

BACKGROUND Comorbid conditions are common and impact outcomes in people with rheumatoid arthritis (RA), but less data are available for psoriatic arthritis (PsA). AIMS To describe baseline demographics and prevalence of comorbidities in participants with PsA in an Australian cohort using data from the Australian Rheumatology Association Database (ARAD) and to compare the prevalence of comorbidities in ARAD participants with PsA with those with RA. METHODS ARAD is a voluntary national registry for inflammatory arthritis. Data, including demographic details, medication use, history of comorbid medical illnesses and patient-reported outcomes, all self-reported, were extracted from questionnaires completed at the time of database enrolment for participants with PsA and RA. Demographic information and prevalence of comorbidities were summarised using descriptive statistics. Prevalence of comorbidities in PsA and RA were compared using logistic regression, adjusting for age, gender, disease duration, education, employment and prednisone use. RESULTS There were 490 participants with PsA, 59.2% female, mean (standard deviation (SD)) age 50.4 (21.1) years and disease duration 16.4 (9.7) years, and 57.8% reported having two or more comorbidities. Hypertension (38.2%) and depression (35.9%) were the most common. Compared with RA, participants with PsA had greater odds of depression (adjusted OR (95% CI): 2.1 (1.7-2.6)), hypertension (1.7 (1.4-2.1)), hyperlipidaemia (2.0 (1.6-2.5)), diabetes (2.2 (1.6-3.0)) and a history of ischaemic heart disease (2.0 (1.3-2.9)). CONCLUSIONS High rates of comorbidity were found in ARAD participants with PsA. The prevalence of depression, cardiovascular risk factors and other comorbidities were higher in PsA than RA participants in our Australian cohort.

Background Glucocorticoids (GCs) are used in ~ 60% of patients with rheumatoid arthritis (RA). Although disease-modifying, they also have significant adverse effects. Understanding factors associated with GC use may help minimise exposure. The aims of the present study were to describe oral GC use in RA; determine any change in use over time; and determine factors associated with oral GC use, commencement or cessation. Methods Adult patients with RA were identified in the Australian Rheumatology Association Database (ARAD), a national Australian registry that collects long-term outcome data from patients with inflammatory arthritis. Patients were categorised by their ARAD date of entry (DOE), with population-averaged logistic regression and transition state analysis used to determine any change in GC use over time. Fixed-effects panel regression was used to examine whether GC current use was associated with pain/arthritis activity/Health Assessment Questionnaire (HAQ) scores or medication use. Transition state analysis was used to assess whether these factors influenced the commencement or cessation of GCs. Results A total of 3699 patients with RA completed a baseline ARAD questionnaire (73% female, mean age 57 years). The probability of GC use decreased over time according to ARAD DOE: September 2001 to March 2005, 55% (95% CI 52–58%); March 2005 to September 2008, 47% (45–49%); September 2008 to March 2012, 42% (39–45%); and March 2012 to October 2015, 39% (34–43%) (p

Background: Tumour necrosis factor-αlpha inhibitors (TNFαi) are the main biologics (b-MARDs) used to treat active rheumatoid arthritis (RA) in patients that have failed disease modifying treatment (DMARD). However, 10% of patients with rheumatoid arthritis, TNFα inhibitors do not work at all. Patients are continued on this treatment for several months risking side-effects in the hope that the treatment will work. Another 40% of patients respond partially to this treatment and have to also be treated with other drugs such as methotrexate and prednisone in addition to treatment with TNFαi. Biomarkers offer an opportunity to identify before starting or soon after starting treatment with TNFαi which patients will be responders and whether prednisone and other drugs can be reduced and optimise the risk-benefit of treatment. Objectives: We undertook a series of experiments with the following objectives: determine whether cytokine biomarkers will predict which patients with rheumatoid arthritis are: (a) sustained DMARD early treatment responders (b) sustained TNFαi early treatment responders, (c) TNFαi early treatment failures. Methods: We used the Millipore’s MILLIPLEX MAP Human Th17 Magnetic Bead kit for the simultaneous quantification of the following cytokines: IL-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL- 12p70, IL-13, IL-15, IL-17A, IL-17E/IL-25, IL-17F, IL-21, IL-22, IL-23, IL-27, IL-28A, IL-31, IL-33, GMCSF, IFNγ, MIP-3α, TNFα and TNFβ. γ, MIP-3α, TNFα and TNFβ. We evaluated 14 patients with RA starting on a DMARD and 26 patients with RA starting on a TNFαi after failing DMARDs. These cytokines were assayed monthly 2 or 3 months prior to starting a TNFαi to evaluate month-to-month cytokine variability and every month up to 5 months after initiation of treatment. RA disease activity was measured using the RA Disease Activity Score (DASCRP28) which includes joint counts, CRP and a patient-reported outcome of health status. All samples were blocked with Heteroblock to reduce rheumatoid factor and other heterophilic antibodies. Rheumatoid factor was measured before and after blocking. The same negative and positive controls were included across all plate runs. All assays were done in singlet to accommodate longitudinal samples. Mixing studies were undertaken to evaluate whether cytokine results could be analysed using quantitative statistics. Results: We had 67 serum samples in the DMARD treated group and 202 serum samples in the TNFαi treated group because of the longitudinal study design. Using mixed effects linear regression to account for longitudinal data in a model that included all 25 cytokines, treatment-time and treatment type (DMARD or TNFαi+/-DMARD), we found that in patients on DMARDs, IL-6, IL-1β, IL-28A, and TNFβ were associated with treatment response. However, in TNFαi treated patients, TNF-a, GM-CSF and IL-6 were associated with treatment response. Only p values Conclusion: In this study of treatment response comparing DMARDs and TNFαi in a longitudinal cohort of 26 patients with a total of 202 samples measuring TNFα and GM-CSF may predict early TNFαi responders. Disclosure of Interests: Marissa Lassere Grant/research support from: I have received research support with educational grant funding from Sanofi-Aventis, Pfizer, MSD, Abbvie, Sue Baker: None declared, Jenny Gu: None declared DOI: 10.1136/annrheumdis-2019-eular.6445

Background Tumour necrosis factor inhibitor (TNFi) therapy has been available for rheumatoid arthritis (RA) patients for several decades but data on the long-term risk of malignancy associated with its use is limited. Our aims were to assess malignancy risk in a cohort of Australian RA patients relative to the Australian population and to compare cancer risk for patients exposed to TNFi therapy versus a biologic-naïve group. Methods Demographic data for RA participants enrolled in the Australian Rheumatology Association Database (ARAD) before 31 Dec 2012 were matched to national cancer records in May 2016 (linkage complete to 2012). Standardised incidence ratios (SIRs) were used to compare malignancy incidence in TNFi-exposed and biologic-naïve ARAD participants with the Australian general population using site-, age- and sex-specific rates by calendar year. Malignancy incidence in TNFi-exposed participants and biologic-naïve RA patients, were compared using rate ratios (RRs), adjusted for age, sex, smoking, methotrexate use and prior malignancy. Results There were 107 malignancies reported after 10,120 person-years in the TNFi-exposed group (N = 2451) and 49 malignancies after 2232 person-years in the biologic-naïve group (N = 574). Compared with the general population, biologic-naïve RA patients showed an increased risk for overall malignancy (SIR 1.52 (95% confidence interval (CI) 1.16, 2.02) prostate cancer (SIR 2.10, 95% CI 1.18, 4.12). The risk of lung cancer was increased for both biologic naïve and TNFi-exposed patients compared with the general population (SIR 2.69 (95% CI 1.43 to 5.68) and SIR 1.69 (95% CI 1.05 to 2.90) respectively). For the TNFi-exposed patients there was an increased risk of lymphoid cancers (SIR 1.82, 95% CI 1.12, 3.18). There were no differences between the exposure groups in the risk of cancer for any of the specific sites examined. Conclusions Overall malignancy incidence was elevated for biologic-naïve RA patients but not for those exposed to TNFi. TNFi exposure did not increase malignancy risk beyond that experienced by biologic-naïve patients. Lung cancer risk was increased for both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status or RA treatments other than TNFi may be responsible in some way.

To determine factors associated with opioid use in rheumatoid arthritis (RA) patients.Adult RA patients (n = 3225, 73% female, mean age 57 years, median follow-up 54 months) were recruited into the Australian Rheumatology Association Database (ARAD) between 2001-2015. A logistic regression examining both within- and between-patient effect sizes for time-varying covariates, and transition-state analysis for covariates associated with opioid commencement or cessation were used to examine determinants of current opioid use.The population-averaged prevalence of any opioid use was 33% (95%CI 32-34), 9% (95% CI 8, 10) for high potency opioid use, and 62% (95% 60, 64) of patients reported opioid ever-use after five years of follow-up. Opioid use was higher in females and decreased with older baseline age. Within-patients opioid use was associated with higher self-reported pain and HAQ scores (p0.001), and NSAID (OR 1.88; 1.67-2.10), oral glucocorticoid (2.23;1.93-2.58), csDMARD (2.08;1.78-2.44) and bDMARD (1.22;1.06-1.40) treatment. Younger baseline age, higher pain scores, HAQ scores and oral GC use were important determinants of change in opioid use, associated with both a higher probability of commencing opioid use, and a lower probability of cessation. Paradoxically, NSAID and DMARD treatments were associated with both a lower probability of commencing opioids, and a lower probability of cessation.There was a high prevalence of opioid use among RA patients, which was associated with pain, function and GC treatment. NSAID, and DMARD treatments obviate the need for opioids in some, but not all, patients.

Background Inflammatory arthritides including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are associated with increased risk of cardiovascular disease. This process may be driven by systemic inflammation, and the use of tumour necrosis factor (TNF) inhibitors could therefore potentially reduce cardiovascular risk by reducing this inflammatory burden. The aims of this study were to evaluate whether the risk of cardiovascular events (CVEs) in patients with inflammatory arthritis is associated with treatment with anti-TNF therapy, compared with other biologics or non-biologic therapy, and to compare the CVE risk between participants with RA, PsA and AS. Methods Data from consecutive participants in the Australian Rheumatology Association Database with RA, PsA and AS from September 2001 to January 2015 were included in the study. The Cox proportional hazards model using the counting process with time-varying covariates tested for risk of having CVEs, defined as angina, myocardial infarction, coronary artery bypass graft, percutaneous coronary intervention, other heart disease, stroke/transient ischaemic attack or death from cardiovascular causes. The model was adjusted for age, sex, diagnosis, methotrexate use, prednisone use, non-steroidal anti-inflammatory use, smoking, alcohol consumption, hypertension, hyperlipidaemia, diabetes and functional status (Health Assessment Questionnaire Disability Score). Results There were 4140 patients included in the analysis, totalling 19,627 patient-years. After multivariate adjustment, the CVE risk was reduced with anti-TNF use (HR 0.85, 95% CI 0.76–0.95) or other biologic therapies (HR 0.81, 95% CI 0.70–0.95), but not in those who had ceased biologic therapy (HR 0.96, 95% CI 0.83–1.11). After adjustment, no significant difference in CVE risk was observed between participants with RA and PsA (HR 0.92, 95% CI 0.77–1.10) or AS (HR 1.14, 95% CI 0.96–1.36). Conclusions Current biologic use was associated with a reduction in major CVEs. No reduction in CVE risk was seen in those who had ceased biologic therapy. After adjustment, the CVE risk was not significantly different between RA, AS or PsA.

IntroductionAcute sciatica (symptom duration less than 4 weeks), a major cause of pain and disability, is a common presentation to medical practices and hospital emergency departments. Selective CT fluoroscopy transforaminal epidural steroid injection is often used with the hope of reducing pain and improving function. Recently, there has been interest in using systemic corticosteroids in acute sciatica. However, there is limited evidence to inform management of selective CT fluoroscopy transforaminal epidural steroid in subacute and chronic sciatica and there is no evidence in acute sciatica, even though the practice is widespread. There is also limited evidence for the use of systemic corticosteroids in acute sciatica. Furthermore, the management of selective CT fluoroscopy transforaminal epidural steroid versus systemic steroids has never been directly studied.Methods and analysisSCIATICA is a pilot/feasibility study of patients with acute sciatica designed to evaluate the feasibility of undertaking a blinded four-arm randomised controlled intervention study of (1) selective CT fluoroscopy transforaminal epidural steroid (arm 1), (2) selective CT fluoroscopy transforaminal epidural saline (arm 2), (3) 15 days tapering dose of oral steroids (arm 3) and (4) a sham epidural and oral placebo control (arm 4). This feasibility study is designed to evaluate head-to-head, route versus pharmacology of interventions. The primary outcome measure is the Oswestry Disability Index (ODI) at 3 weeks. Secondary outcome is the ODI at 48 weeks. Other outcomes include numerical rating scale for leg pain, Pain DETECT Questionnaire, quality of life, medication use, rescue procedures or surgery, and adverse events. Results of outcomes from this randomised controlled trial will be used to determine the feasibility, sample size and power calculations for a large multicentre study.Ethics and disseminationThe study has been approved by South Eastern Sydney Local Health District Human Research Ethics Committee (HREC/15/331/POHW/586).Trial registration numberNCT03240783; Pre-results.

Background Chronic inflammatory arthritis is associated with increased cardiovascular (CV) morbidity and mortality. Pharmacological management and healthy lifestyle modification is recommended to manage these risks, but it is not known how often these are utilised and whether there is any difference in their use between patients with different types of arthritis. The aim of this study was to determine and compare the proportion of participants with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) receiving pharmacological or lifestyle management strategies for CV risk factors. The secondary objective was to identify factors associated with use of management strategies. Methods A survey was sent to online participants in the Australian Rheumatology Association Database, a voluntary national registry for inflammatory arthritis. Participants were asked whether they took medications for hypertension, hyperlipidaemia and diabetes, and to report their height, weight, level of physical activity, and dietary changes made. The use of management strategies was compared between participants with RA and PsA. Logistic regression analyses were performed to identify factors associated with physical activity and dietary changes. Results There were 858 respondents with RA and 161 with PsA (response rate 64.5%). Pharmacological treatment was reported by 93% of participants with hypertension and 70% with hyperlipidaemia. All participants with diabetes reported being managed with dietary modification, pharmacological treatment, or a combination of both. Adequate physical activity was reported by 50.8%. Only 27% of overweight or obese participants reported making any dietary change for their health in the past year. There was no difference between RA and PsA in reported utilisation of management strategies. Hyperlipidaemia and being overweight were associated with making dietary change. Obesity and arthritis disease activity were negatively associated with physical activity. Conclusions Most participants with RA and PsA reported using pharmacological treatment for CV risk factors. Relatively few reported using lifestyle modifications. Targeted lifestyle interventions should be implemented for RA and PsA patients. Electronic supplementary material The online version of this article (10.1186/s41927-018-0032-9) contains supplementary material, which is available to authorized users.

Objective.To describe the ways in which serum urate (SU) and gout flares are reported in clinical trials, and to propose minimum reporting requirements.Methods.This analysis was done as part of a systematic review aiming to validate SU as a biomarker for gout. The ways in which SU and flares were reported were extracted from each study by 2 reviewers.Results.A total of 22 studies (10 randomized controlled trials, 3 open-label extension studies, and 9 observational studies) were identified. There were 3 broad categories of SU reporting: percentage at target SU, mean SU, and change in SU. A median of 2 (range 1–3) categories were reported across all studies. The most common method of reporting SU was percentage at target in 17/22 (77.3%) studies, with all studies reporting a target of SU < 6 mg/dl. There were 12/22 (54.5%) studies reporting mean SU at some time after study entry, with 7 (58.3%) of these reporting at more than just the final study visit. Two ways of reporting gout flares were identified: mean flare rate and percentage of participants with flares. There was variability in time periods over which flares rates were reported.Conclusion.There is inconsistent reporting of SU and flares in gout studies. Reporting the percentage of participants who achieve a target SU reflects international treatment guidelines. SU should also be reported as a continuous variable with a relevant central and dispersion estimate. Gout flares should be reported as both percentage of participants and mean flare rates at each timepoint.

There is no published support of validity of progression-free survival (PFS) in metastatic renal cell (mRCC) disease. We determine the surrogate threshold effect, the PFS difference needed to predict with 95% confidence an overall survival (OS) benefit in targeted therapy trials. A new such trial with a 3.9 month PFS difference can claim OS benefit. Regulatory use of PFS evidence in mRCC is reviewed. Background In metastatic renal cell cancer (mRCC) trials, progression-free survival (PFS) is increasingly used instead of overall survival (OS) as the approval end point. Unlike other solid tumors, there is no published demonstration of what PFS is needed across and by treatment class in mRCC. We determine this and evaluate drug approval decisions in mRCC targeted therapy. Methods We identified all randomized, controlled trials reporting PFS and OS in mRCC. Surrogacy metrics were the coefficient of determination and surrogate threshold effect (STE)—the PFS difference needed to predict, with 95% confidence, an OS difference. Data from regulatory commentaries, briefing documents and transcripts were extracted. Results No exclusively chemotherapy trial met criteria. Of 30 qualifying trials, 11 trials (13 comparisons) used targeted therapy. The all-trials and immunotherapy-only trials analysis failed to demonstrate a STE. The targeted trials, using the more conservative regression analysis demonstrated an STE of 3.9 months and anR2 of 0.44. Crossover upon progression, control to active treatment, was common. Regulatory approval, accelerated or regular, labeling, interim analyses, and adjudication were context specific. Conclusions A new targeted therapy trial showing a PFS difference of 3.9 months can claim an OS benefit in mRCC. PFS surrogacy for OS in metastatic renal cell is not generalizable across all drug classes.

Aim To determine whether exposure to tumour necrosis factor (TNF)-α inhibitors increases the risk of herpes zoster (HZ) among people with rheumatoid arthritis (RA). Methods We performed a cohort study of people with RA participating in the Australian Rheumatology Association Database. We identified self-reported cases of HZ and verified using medical records. For the primary analysis, we only included doctor-verified cases. For TNF-α inhibitor exposed groups, we excluded HZ episodes that occurred before TNF-α inhibitor initiation, and for the control group we excluded HZ episodes that occurred prior to 2000 or RA diagnosis. The risk of HZ among participants exposed versus not exposed to TNF-α inhibitors was compared using Cox proportional hazards models including significant covariates affecting the risk. Adjusted hazard ratios (HR) were calculated for TNF inhibitors as a class and for individual agents. Results Among 2157 active RA participants, there were 442 self-reported cases of HZ. From 346 responses from doctors, 249 cases were verified and four were false positives (false positive rate 1.6%). Crude incidence of verified HZ in the entire RA cohort was 15.9/1000 person-years (95% confidence interval (CI): 13.5–18.8). An increased risk of HZ was found for all TNF-α inhibitors combined (fully adjusted HR 1.71; 95% CI: 1.00–2.92) and adalimumab (fully adjusted HR 2.33; 95% CI: 1.22–4.45), but in the fully adjusted model was not increased with etanercept (fully adjusted HR 1.65; 95% CI: 0.90–3.03). No increased risk was found with infliximab (HR 1.29; 95% CI: 0.37–4.47). Conclusions TNF-α inhibitors are associated with an increased risk of HZ in people with RA compared with those who have not been exposed.

OBJECTIVES: The primary efficacy outcome in trials of urate lowering therapy (ULT) for gout is serum urate (SU). The aim of this study was to examine the strength of the relationship between SU and patient-important outcomes to determine whether SU is an adequate surrogate endpoint for clinical trials.METHODS: Multiple databases through October 2017 were searched. Randomized controlled trials comparing any ULT in people with gout with any control or placebo, ≥three months duration were included. Open label extension (OLE) trial data were included in secondary analyses. Standardized data elements were extracted independently by two reviewers.RESULTS: Ten RCTs and 3 OLE studies were identified. From the RCTs (maximum duration 24 months) meta-regression did not reveal an association between the relative risk of a gout flare and the difference in proportions of individuals with SU < 6mg/dL (P = 0.47; R 2 = 8%). In a post hoc analysis, the ratio of the time in months at which the proportion of individuals having a flare was reported/time in months at which the proportion of individuals with SU < 6mg/dL was reported was calculated and studies where the ratio was CONCLUSIONS: Based on aggregate clinical trial-level data an association between SU and gout flare could not be confirmed. However, based on observational ecological study design data-including longer duration extension studies-SU < 6mg/dL was associated with reduced gout flares.

Objective To compare the relative effectiveness of anti–tumor necrosis factor (anti-TNF) therapies on health-related quality of life (HRQOL) by inflammatory arthritis types. Methods Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) who had anti-TNF therapy (etanercept, adalimumab, or infliximab) in the Australian Rheumatology Association Database during 2001–2011 were assessed using the Medical Outcomes Study Short Form 36 (SF-36), Assessment of Quality of Life (AQoL), and Health Assessment Questionnaire (HAQ) disability index (DI) on a biannual basis. Linear regression was used for the analysis; the lack of independence in outcomes for multiple assessments in the same patient was taken into account using generalized estimating equations. Results There were 18,119 assessments (first-time drug use n = 12,274, subsequent use n = 3,098, and no use n = 2,747) provided by 3,033 patients (2,240 RA, 507 AS, and 286 PsA patients) with the anti-TNF therapies. The effects of subsequent use versus first-time use were reduced on the SF-36 physical component summary, AQoL, and HAQ DI scores among RA patients. After adjusting for therapy order, calendar year, sex, age, smoking status, and various medication uses, the 3 anti-TNF preparations had similar effects on the HRQOL measures for patients with RA, AS, or PsA. However, differences between anti-TNF therapies were observed in the AQoL score among PsA patients (infliximab versus etanercept: −0.06 [95% confidence interval (95% CI) −0.12, −0.004]) and in the SF-36 mental component summary score among RA patients (adalimumab versus etanercept: −1.17 [95% CI −1.88, −0.46]). Conclusion This study revealed similar effectiveness of etanercept, adalimumab, and infliximab on the HRQOL measures among Australians with RA, AS, and PsA.

Background There is an excess of mortality in patients with rheumatoid arthritis (RA) but no long-term Australian cohort data. Aims To determine median life years lost, all-cause standardised mortality ratio (SMR) and cause-specific SMR, their predictors and secular change in Australian patients with RA. Methods Study population was all patients seen by a rheumatologist between 1990 and 1994. Record linkage with Australian National Death Index was performed to determine fact and cause of death up to 2004. All-cause and cause-specific SMR, and median life years lost were determined. Results There were 35 (31%) deaths in the early 1990s cohort (n = 113), SMR 1.31 (95% 0.93, 1.80). There were 216 (44%) deaths in the pre-1990s established cohort (n = 495), SMR 1.73 (1.49, 1.95). Median life years lost in the early cohort was 6 years for males and 7 years for females compared with 8 and 10 years, respectively, in the established cohort. Patients with low disease activity score at baseline (DAS < 3.2), SMR was 0.8 (0.3, 2.2) and 1.5 (1.1, 2.2) for the early and established cohorts, and if DAS ≥3.2, SMR was 1.4 (1.02, 1.98) and 1.8 (1.5, 2.1) respectively. Primary cause of death was cardiovascular disease (SMR 1.43 (1.17, 1.74). Patients at most risk were those age 45–54 years. RA was listed as a comorbid condition on the death certificate in only 16% of patients. Conclusions Within a period of 14 years, median life expectancy of patients with RA with disease onset in the early 1990s is reduced by 6–7 years. However, our results also suggest a secular reduction in excess mortality.

Aims The aim of this study was to evaluate whether a real-time (RT) colour pictorial radiation dose monitoring system reduces patient skin and total radiation dose during coronary angiography and intervention. Methods and results Patient demographics, procedural variables and radiation parameters were recorded before and after institution of the RT skin dose recording system. Peak skin dose as well as traditionally available measures of procedural radiation dose were compared. A total of 1,077 consecutive patients underwent coronary angiography, of whom 460 also had PCI. Institution of the RT skin dose recording system resulted in a 22% reduction in peak skin dose after accounting for confounding variables. Radiation dose reduction was most pronounced in those having PCI but was also seen over a range of subgroups including those with prior coronary artery bypass surgery, high BMI, and with radial arterial access. This was associated with a significant reduction in the number of patients placed at risk of skin damage. Similar reductions in parameters reflective of total radiation dose were also demonstrated after institution of RT radiation monitoring. Conclusions Institution of an RT skin dose recording reduced patient peak skin and total radiation dose during coronary angiography and intervention. Consideration should be given to widespread adoption of this technology.

Contains fulltext : 171906.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Gout is the most common inflammatory arthritis in men over 40 years of age. Long-term urate-lowering therapy is considered a key strategy for effective gout management. The primary outcome measure for efficacy in clinical trials of urate-lowering therapy is serum urate levels, effectively acting as a surrogate for patient-centred outcomes such as frequency of gout attacks or pain. Yet it is not clearly demonstrated that the strength of the relationship between serum urate and clinically relevant outcomes is sufficiently strong for serum urate to be considered an adequate surrogate. Our objective is to investigate the strength of the relationship between changes in serum urate in randomised controlled trials and changes in clinically relevant outcomes according to the 'Biomarker-Surrogacy Evaluation Schema version 3' (BSES3), documenting the validity of selected instruments by applying the 'OMERACT Filter 2.0'. METHODS AND ANALYSIS: A systematic review described in terms of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will identify all relevant studies. Standardised data elements will be extracted from each study by 2 independent reviewers and disagreements are resolved by discussion. The data will be analysed by meta-regression of the between-arm differences in the change in serum urate level (independent variable) from baseline to 3 months (or 6 and 12 months if 3-month values are not available) against flare rate, tophus size and number and pain at the final study visit (dependent variables). ETHICS AND DISSEMINATION: This study will not require specific ethics approval since it is based on analysis of published (aggregated) data. The intended audience will include healthcare researchers, policymakers and clinicians. Results of the study will be disseminated by peer-reviewed publications. TRIAL REGISTRATION NUMBER: CRD42016026991.

Objective.In rheumatoid arthritis (RA), radiographic progression may occur despite clinical remission. This may be explained by subclinical inflammation. Magnetic resonance imaging (MRI) provides a greater sensitivity than clinical examination and radiography for assessing disease activity. Our objective was to determine the MRI characteristics of RA patients in clinical remission or low disease activity (LDA) state.Methods.Databases from 6 cohorts were collected from 5 international centers. RA patients in clinical remission according to Disease Activity Score28-C-reactive protein (DAS28-CRP < 2.6; n = 213) or LDA-state (2.6 ≤ DAS28-CRP < 3.2; n = 81) with available MRI data were included. MRI were assessed according to the OMERACT RA MRI scoring system (RAMRIS).Results.Patient characteristics: 70% women, median age 55 (interquartile range, IQR 43–63) years, disease duration 2.3 (IQR 0.7–5.1) years, DAS28-CRP 2.2 (IQR 1.8–2.6), Simplified Disease Activity Index, SDAI, 3.9 (IQR 1.9–6.5), Clinical Disease Activity Index, CDAI, 3.1 (IQR 1.5– 5.8), rheumatoid factor/anti-cyclic citrullinated peptide positivity 57%/54%, presence of radiographic erosions: 66%. Wrist and metacarpophalangeal MRI (MCP-MRI) data were available for 287 and 241 patients, respectively. MRI inflammatory activity in wrist and/or MCP joints was observed in the majority [synovitis: 95%, bone edema (osteitis): 35%] of patients. The median (IQR) RAMRIS score was 6 (3–9) for synovitis and 0 (0–2) for osteitis. Synovitis and osteitis were not less frequent in DAS28 clinical remission (synovitis/osteitis 96%/35%) than LDA (91/36). A trend towards lower frequencies of osteitis in patients in SDAI and CDAI remission was observed.Conclusion.Subclinical inflammation was identified by MRI in the majority of RA patients in clinical remission or LDA state. This may explain structural progression in such patients. Further work is required to understand the place of modern imaging in future remission criteria.

Objective To elicit patients’ views on whether they could contribute to improvements in their care by carrying their own health information to clinician encounters; and to consider the implications for the development of a patient-held health file (PHF). Background Increasing rates of chronic disease lead to health care being delivered by multiple care providers often at distributed geographic locations. As a way of increasing the availability of patient information to care providers our project will trial a PHF. Patients carry these files to doctors’ appointments where clinicians record data for other doctors or the patient. Increasing the availability of patient information is anticipated to enhance the safety and quality of care delivery and improve health outcomes. Study design Qualitative semi-structured interviews were conducted with 10 patients. Participants were evenly distributed in terms of gender, aged 60 years or greater and visited at least two specialists and one general practitioner. Findings In this exploratory study, patients who were currently active in decision making about their own health already recorded some health information. They were receptive to carrying their information and thought they should take some responsibility for their health. Patients who were more passive in making decisions about their health did not perceive a need to carry their own information and felt that their doctors communicated adequately. Conclusion Patient-held health files provide an opportunity for patients to access their health information. Such files have the potential to improve health outcomes for patients who adopt both active and passive roles in relation to their own health and engaging with their health information.

This narrative review outlines the work done in other fields with regards biomarker validation and qualification and the lessons that we may learn from this experience. Defining a universally agreed upon path for biomarker validation and qualification is urgently needed to circumvent many of the hurdles faced in OA therapeutic development irrespective of whether we are discussing biochemical markers, imaging markers or other measures. This review proposes a path that may be suitable for osteoarthritis and poses some logical next steps that will take us in this direction.

Magnetic resonance imaging (MRI) provides an important biomarker across a range of rheumatological diseases. At the Outcome Measures in Rheumatology (OMERACT) 11 meeting, the MRI task force continued its work of developing and improving the use of MRI outcomes for use in clinical trials. The breadth of pathology in the Rheumatoid Arthritis MRI Score has been strengthened with further work on the development of a joint space narrowing score, and a series of exercises presented at OMERACT 11 demonstrated good reliability and construct validity for this assessment. Understanding the importance of residual inflammation after RA treatment remains a major focus of the group’s work. Analyses were presented on defining the level of synovitis (using MRI scores of a single hand) that would predict absence of erosion progression. The development of the OMERACT Hand Osteoarthritis MRI score has continued with substantial work presented on its iterative development, including pathology definition, scaling, and subsequent reliability of the score. Optimizing the role of MRI as a robust biomarker and surrogate outcome remains a priority for this group.

Objective.Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) provides highly sensitive assessment of inflammatory and destructive changes in rheumatoid arthritis (RA) joints, but intravenous (IV) Gd injection prolongs examination time and increases cost, invasiveness, and patient discomfort. We explored to what extent RA joint pathologies in wrists and metacarpophalangeal (MCP) joints can be reliably assessed by unenhanced MRI images compared with Gd-enhanced MRI as the reference method.Methods.MRI data sets from 2 RA substudies were scored according to preliminary OMERACT RA MRI scoring system (RAMRIS): Substudy A included 1.0 T/1.5 T MR images from 40 RA patients, which were scored twice by 2 experienced readers. Substudy B included 0.2 T dedicated extremity MRI (E-MRI) images from 55 patients, scored twice by one experienced reader. The first reading included only unenhanced images, whereas complete image sets were available for the second reading.Results.Gd contrast injection appeared unimportant to MRI scores of bone erosions and bone edema in RA wrist and MCP joints. However, when post-Gd MRI was considered the standard reference, MRI without Gd provided only moderate to high agreement concerning assessment of synovitis, and omitting the post-Gd acquisitions increased the interreader variation on synovitis scores. Low-field (0.2 T) E-MRI in these exercises provided a lower sensitivity of unenhanced imaging for synovitis than MRI using higher-field strengths.Conclusion.Omitting IV contrast injection did not change scores of bone erosions and bone edema, but decreased the reliability of synovitis scores. However, this disadvantage may for some purposes be outweighed by the possibility to assess more joints and/or greater feasibility.

Background: The Australian Rheumatology Association Database (ARAD) is a voluntary national registry for monitoring the long-term benefits and safety of biological disease-modifying anti-rheumatic drugs (bDMARDs) for inflammatory arthritis. Both rheumatologists and patients contribute data to the ARAD. Objective: To evaluate the satisfaction of patients and rheumatologists with the ARAD. Methods: Cross-sectional surveys were distributed to a random sample of 100 community-dwelling ARAD patients in 2007 and to rheumatologists attending the 2007 Australian Rheumatology Association (ARA) annual scientific meeting. Survey questions included items about the usefulness of the ARAD, workload for participants, frequency of questionnaires, and experience of contact with ARAD staff. Results: A total of 92.5% of patients perceived the ARAD as very important (scoring 9–10 on a numeric rating scale). Patients reported minimal difficulty in completing questionnaires, and 95.0% indicated that a 6-month interval between questionnaires was reasonable. Of responding rheumatologists, 32.3%, 62.1%, and 53.8% indicated that the ARAD was very important (scoring 8–10) with respect to clinical information, research, and the profession, respectively, while 68% of those participating in the ARAD reported that the workload required to enroll patients was manageable and 30% found it difficult or onerous. Conclusion: Key stakeholders in the ARAD view it as an important resource and are satisfied with its operations. Efforts will be directed towards assisting those rheumatologists who find the associated workload difficult and to improving the perceived clinical value of information available from the ARAD.

Objective We describe a new statistical method called the surrogate threshold effect (STE) that estimates the threshold level of a surrogate needed in a clinical trial to predict a benefit in the target clinical outcome. In this article, we apply this method to the LDL-cholesterol biomarker surrogate and survival benefit-target outcome in statin trials. Study Design and Setting We identified randomized trials comparing statin treatment to placebo treatment or no treatment and reporting all-cause and cardiovascular mortality. Trials with fewer than five all-cause deaths in at least one arm were excluded. Multiple regression modeled the reduction in all-cause and cardiovascular mortality as a function of LDL-cholesterol difference. The 95% confidence and 95% prediction bands were calculated and graphed to determine the minimum LDL-cholesterol difference (the surrogate threshold) below which there would be no predicted survival benefit. Results In 16 qualifying trials, regression analysis yielded an all-cause mortality model whose prediction bands demonstrated no overall survival gain with LDL-cholesterol difference values below 1.5 mmol/L. The cardiovascular mortality model yielded prediction bands that demonstrated no cardiovascular survival benefit with LDL-cholesterol difference values below 1.4 mmol/L. Conclusions In a multitrial setting, the STE approach is a promising yet straightforward statistical method for evaluating the surrogate validity of biomarkers.

The five stages in the evolution of a new method or measure are discovery (by design or inadvertent), development, testing, standardization and application. However, measures may be accepted, disseminated and used before they have been formally evaluated and standardized. This chapter describes the properties of measurement in the medical sciences and the process of standardization. It includes an example of the development and standardization of a magnetic resonance imaging rheumatoid arthritis score, and ends with a matrix that can serve as a guide for systematic appraisal and standardization of outcome measures, such as imaging outcomes. Using the matrix, one can determine the gaps in knowledge and what further evaluation is needed in one or more domains or metrics.

Background: The Australian Rheumatology Association Database (ARAD), a voluntary national registry, has been established to collect health information from Australian patients with inflammatory arthritis for the purpose of monitoring the benefits and safety of new treatments, in particular the biological disease-modifying anti-rheumatic drugs (bDMARDs). These drugs are proving to be very effective, yet little is known of their long-term effectiveness or safety. Patient registries that systematically gather data on large cohorts of unselected patients are increasingly believed to be an essential means of answering questions of the long-term effectiveness and safety of new drugs. The aim of this report is to describe the role, development and structure of ARAD and provide some preliminary data. Methods: As of 1 August 2006, 563 patients with rheumatoid arthritis prescribedabDMARDhavebeenenrolledinARAD,involving105rheumatologists from across Australia. Results: The data collected will enable examination of multiple domains of patient responses to bDMARDs, including quality of life, health-care utilization, incidence of adverse events and the effects of therapy switching. Conclusion: Evidence-based information about the long-term outcome of bDMARD therapy is essential for clinicians, consumers, policy-makers, drug development companies and approval agencies, to enable better care and improved outcomes for patients with inflammatory arthritis.

Summary Introduction Arthroscopy has been used to evaluate articular cartilage (AC) pathology in osteoarthritis (OA) for outcome measurement and validation of non-invasive imaging. However, many fundamental aspects of arthroscopic assessment remain un-validated. Objectives This study evaluated arthroscopic estimates of extent of chondropathy. Methods Serial arthroscopic assessments were performed in a group of 15 sheep before and after bilateral stifle medial meniscectomy (MMx). Post-mortem assessments were performed in un-MMx sheep and 4 and 16 weeks post-MMx. Arthroscopic assessments of the extent of each grade of chondropathy were compared with a non-arthroscopic hybrid assessment that incorporated biomechanical, thickness and macroscopic assessments. Results Arthroscopy evaluated only 36% of AC and missed significant pathological changes, softening and chondro-osteophyte, occurring in peripheral regions. The patterns of change in arthroscopic assessments were similar to those of the non-arthroscopic assessment but there was a very strong tendency to over-estimate the extent of softened AC after MMx. In spite of these limitations arthroscopic assessments were responsive to change. Estimates of the extent of normal and softened AC were most responsive to change over time followed by estimates of superficial and deep fibrillation. Arthroscopy was as an excellent discriminator between normal and OA. Assessments of chondro-osteophyte and exposed bone were not responsive to change. Conclusions Arthroscopic estimates of extent of chondropathy are prone to substantial error. While experience and training may reduce these errors other approaches may more effectively improve performance.

Background Malignancy risk with tumour necrosis factor inhibitor (TNFi) therapy remains unclear. Our primary aim was to assess malignancy risk with TNFi therapy in a cohort of Australian patients with rheumatoid arthritis (RA). We also assessed risk in a biologic-naïve group. Methods Demographic data of all RA patients enrolled in the Australian Rheumatology Association Database before 25 October 2010 were matched to national cancer records in July 2010 (linkage complete to 2007). Verified self-reported malignancies occurring between 1 January 2008 and 25 October 2010 were also included in the analysis. Standardised incidence ratios (SIRs) were used to compare malignancy incidence in biologic-naïve and TNFi-exposed ARAD participants to the general population using site-, age- and sex-specific rates by calendar year. Rate ratios (RRs) were used to compare malignancy incidence in TNFi-exposed participants to biologic-naïve RA patients, and a composite RA cohort that included pre-TNFi person years, both adjusted for age, gender, smoking, methotrexate use and prior malignancy. Results Forty-four malignancies were reported after 5752 person-years in the TNFi-exposed group (N = 2145) and 32 malignancies were reported after 1682 person-years in the biologic-naïve group (N = 803). No overall increased risk of malignancy in TNFi-treated RA patients was found when compared with the general population or with biologic-naïve RA patients. Compared to the biologic naïve group, without the inclusion of pre-TNFi years in the comparator group, the relative risk of female breast cancer was reduced in TNFi-treated patients (RR 0.17 (95 % CI 0.03 to 0.95)). It was no longer significant when adding pre-TNFi years in the comparator group. The risk of melanoma was increased for both biologic naïve and TNFi-treated patients when compared with the general population (SIR 2.72 (95 % CI 1.13 to 6.53) and SIR 2.03 (95 % CI 1.09 to 3.78) respectively). The relative risk of melanoma was not increased in the TNFi-exposed group compared with biologic naïve patients (RR 0.54, 95 % CI 0.12, 2.40). Inclusion of pre-TNFi person years in the comparator group did not change these results. Conclusions Malignancy incidence was low in this RA cohort and biologic exposure did not increase the risk of malignancy. Melanoma risk was increased in both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible.

Objective To evaluate the performance characteristics of power Doppler ultrasound as a diagnostic and monitoring tool in the assessment of musculoskeletal disease through a systematic review of the literature. Methods Search Strategy: We performed a literature search of PUBMED (1966 to June 2005). Selection Criteria: Only original research reports written in English involving musculoskeletal disease and power Doppler ultrasound were included. Reviews were noted but not included. Data Extraction/Reporting: The design, subjects, methods, imaging protocols, and performance characteristics studied in the research papers were reported. Results Of 3568 identified reports, 139 involved power Doppler ultrasound of the musculoskeletal system. Fifty-three of these reports met the inclusion criteria. Ultrasound machine settings were specified in 63% of reports. Rheumatoid arthritis was the most commonly studied musculoskeletal disease (64% of papers). Validity was the most studied performance characteristic (94% of reports), while reliability and responsiveness were studied in 17 and 34%, respectively. Conclusions Although the majority of research reports of power Doppler ultrasound assessment of the musculoskeletal system evaluated validity, less than half reported reliability and responsiveness. Further work is needed to evaluate power Doppler ultrasound assessment of the musculoskeletal system before it can be used to guide clinical decisions or be used as an endpoint in clinical trials.