Interpersonal process of dyadic coping in rheumatoid arthritis: a perspective from the Australian Rheumatology Association Database (ARAD).

OBJECTIVE: Dyadic coping, the process of coping that transpires between couples challenged by one partner's illness, is an important predictor of disease adjustment and patient wellbeing. However, dyadic coping in rheumatoid arthritis remains unclear. This study examines the effect of dyadic coping on psychological distress and relationship quality from both participants with rheumatoid arthritis as well as their spouse's perspective. METHODS: Participants and their spouses were invited to participate in an online survey study if they were 18+ years and had lived together for more than a year. The survey included the Dyadic Coping Inventory, Depression, Anxiety and Stress Scale and Dyadic Adjustment Scale. Participants and spouses completed the survey independently. The actor-partner interdependence model was used to analyze the dyadic data. RESULTS: 163 couples participated. Our findings showed that participants who reported higher supportive dyadic coping reported lower depression, anxiety, stress and higher relationship quality. While participants who reported higher negative dyadic coping reported higher depression, anxiety, stress and lower relationship quality. Spouses who reported higher supportive dyadic coping reported higher relationship quality but no impact on depression, anxiety and stress was observed. However, spouses who reported higher negative dyadic coping reported higher levels of depression, anxiety and stress and lower relationship quality. CONCLUSION: Participants and spouse's own views of supportive and negative dyadic coping they receive intimately affects their psychological distress and relationship quality. Also, having a partner with rheumatoid arthritis also seemed to impact the spouse especially when there was a negative dyadic coping pattern.

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded.

Trajectories of self-reported pain-related health outcomes and longitudinal effects on medication use in rheumatoid arthritis: a prospective cohort analysis using the Australian Rheumatology Association Database (ARAD).

OBJECTIVE: To determine distinct trajectories of self-reported pain-related health status in rheumatoid arthritis (RA), their relationship with sociodemographic factors and medication use. METHODS: 988 Australian Rheumatology Association Database participants with RA (71% female, mean age 54 years, mean disease duration 2.3 years) were included. Distinct multi-trajectories over 15-year follow-up for five different self-reported pain-related health outcome measures (Health Assessment Questionnaire Disability Index, visual analogue scores for pain, arthritis, global health and the Assessment of Quality of Life utility index) were identified using latent variable discrete mixture modelling. Random effects models were used to determine associations with medication use and biologic therapy modification during follow-up. RESULTS: Four, approximately equally sized, pain/health status groups were identified, ranging from 'better' to 'poorer', within which changes over time were relatively small. Important determinants of those with poorer pain/health status included female gender, obesity, smoking, socioeconomic indicators and comorbidities. While biologic therapy use was similar between groups during follow-up, biologic therapy modifications (plinear<0.001) and greater tendency of non-tumour necrosis factor inhibitor use (plinear<0.001) were observed in those with poorer pain/health status. Similarly, greater use of opioids, prednisolone and non-steroidal anti-inflammatory drugs was seen in those with poorer pain/health status. CONCLUSION: In the absence of disease activity information, distinct trajectories of varying pain/health status were seen from the outset and throughout the disease course in this RA cohort. More biologic therapy modifications and greater use in anti-inflammatories, opioids and prednisolone were seen in those with poorer pain/health status, reflecting undesirable lived experience of persistent pain in RA.

Mortality estimates and excess mortality in rheumatoid arthritis.

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.

COVID-19 vaccine hesitancy in inflammatory arthritis patients: serial surveys from a large longitudinal national Australian cohort.

OBJECTIVES: To determine COVID-19 vaccine hesitancy rates in inflammatory arthritis patients and identify factors associated with changing vaccine hesitancy over time. METHODS: This investigation was a prospective cohort study of inflammatory arthritis patients from community and public hospital outpatient rheumatology clinics enrolled in the Australian Rheumatology Association Database (ARAD). Two surveys were conducted, one immediately prior to (pre-pandemic) and another approximately 1 year after the start of the pandemic (follow-up). Coronavirus disease 2019 (COVID-19) vaccine hesitancy was measured at follow-up, and general vaccine hesitancy was inferred pre-pandemic; these were used to identify factors associated with fixed and changing vaccine beliefs, including sources of information and broader beliefs about medication. RESULTS: Of the 594 participants who completed both surveys, 74 (12%) were COVID-19 vaccine hesitant. This was associated with pre-pandemic beliefs about medications being harmful (P < 0.001) and overused (P = 0.002), with stronger beliefs resulting in vaccine hesitancy persistent over two time points (P = 0.008, P = 0.005). For those not vaccine hesitant pre-pandemic, the development of COVID-19 vaccine hesitancy was associated with a lower likelihood of seeking out vaccine information from health-care professionals (P < 0.001). COVID-19 vaccine hesitancy was not associated with new influenza vaccine hesitancy (P = 0.138). CONCLUSION: In this study of vaccine beliefs before and during the COVID-19 pandemic, factors associated with COVID-19 vaccine hesitancy in inflammatory arthritis patients varied, depending on vaccine attitudes immediately prior to the start of the pandemic. Fixed beliefs reflected broader views about medications, while fluid beliefs were highly influenced by whether they sought out information from health-care professionals, including rheumatologists.

Patterns of biologic and targeted-synthetic disease-modifying antirheumatic drug use in rheumatoid arthritis in Australia.

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.

A Versatile, Secure, and Sustainable All-in-One Biobank-Registry Data Solution: The A3BC REDCap Model.

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 multisite biobank registry with complex longitudinal sample and data requirements. Materials and Methods: We assessed several international commercial and nonprofit software platforms using standardized system requirement criteria and follow-up interviews. Vendor compliance scoring was prioritized to meet our project-critical requirements. Consumer/end-user codesign was integral to refining our system requirements for optimized adoption. Customization of the selected software solution was performed to optimize field auto-population between participant timepoints and forms, using modules that are transferable and that 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 nonprofit license agreement terms), highly configurable, and customizable 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: (1) best practice data security measures (incl. multisite access login using institutional user credentials), (2) permission-to-contact and dynamic itemized electronic consent, (3) a complete chain of custody from consent to longitudinal biospecimen data collection to publication, (4) complex longitudinal patient-reported surveys, (5) integration of record-level extracted/linked participant data, (6) significant form auto-population for streamlined data capture, and (7) native dashboards for operational visualizations. 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.

Serum urate as a proposed surrogate outcome measure in gout trials: From the OMERACT working group.

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).

Corticosteroid Use and Risk of Herpes Zoster in a Population-Based Cohort.

OBJECTIVE: To examine the relationship between corticosteroid use and herpes zoster risk. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Use of disease-modifying antirheumatic drugs and the subsequent risk of herpes zoster in older adults.

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 < 0.001; reference: non-users). Among users of csDMARDs, compared with non-users, zoster risks were highest in those using exclusively cyclophosphamide (aHR 2.69 [95% CI: 1.89, 3.83]), more moderate in those using azathioprine (aHR 1.57 [95% CI: 1.07, 2.30]) and hydroxychloroquine (aHR 1.43 [95%CI: 1.11, 1.83]) and not elevated in users of methotrexate (aHR 1.24 [95% CI: 0.98, 1.57]), sulfasalazine (aHR 1.00 [95% CI: 0.71, 1.42]) and leflunomide (aHR 0.41 [95% CI: 0.06, 2.88]). 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.

Healthcare access and attitudes towards telehealth during the early phase of the COVID-19 pandemic among an Australian cohort with inflammatory arthritis.

Community restrictions due to COVID-19 have changed healthcare, including increased telehealth use. During the early pandemic phase, a cohort of Australian patients with inflammatory arthritis was surveyed. Self-reported access to healthcare was maintained and physical health was more likely to be self-rated poorly than mental health. There was a high level of support for telehealth during and after the pandemic.

Oral Complementary Medicine Use among People with Inflammatory Arthritis: An Australian Rheumatology Association Database Analysis.

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.

Bias, coverage, and asymptotic behaviour of random effects meta-analysis: a clinically driven simulation study.

AIMS: The 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. METHODS: With 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. RESULTS: Bias, 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. CONCLUSION: The 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.

Factors associated with commencing and ceasing opioid therapy in patients with rheumatoid arthritis.

OBJECTIVE: To determine factors associated with opioid use in rheumatoid arthritis (RA) patients. METHODS: 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. RESULTS: 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 (p < 0.001), 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. CONCLUSIONS: 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.

Investigating Dimensions of Stiffness in Rheumatoid and Psoriatic Arthritis: The Australian Rheumatology Association Database Registry and OMERACT Collaboration.

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.

Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: an update from the Australian Rheumatology Association Database (ARAD) prospective cohort study.

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.

Biologics and cardiovascular events in inflammatory arthritis: a prospective national cohort study.

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.

Comorbidity in psoriatic arthritis and rheumatoid arthritis.

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.

Protocol of the randomised placebo controlled pilot trial of the management of acute sciatica (SCIATICA): a feasibility study.

INTRODUCTION: Acute 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 ANALYSIS: SCIATICA 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 DISSEMINATION: The study has been approved by South Eastern Sydney Local Health District Human Research Ethics Committee (HREC/15/331/POHW/586). TRIAL REGISTRATION NUMBER: NCT03240783; Pre-results.

Serum urate as surrogate endpoint for flares in people with gout: A systematic review and meta-regression analysis.

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; R2 = 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 <2 were excluded. Using the remaining 6 studies there was an association between proportion of individuals achieving SU < 6mg/dL and gout flares (over patient years). Duration of ULT was inversely associated with the proportion of patients experiencing a flare. Study duration and variability in reporting of outcomes limited the analysis. Observational studies supported the trend of fewer flares in those with lower SU. 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.