Centre for Epidemiology Versus Arthritis

PURPOSE: To estimate the prevalence of metabolic syndrome (MetS) in the US National Health and Nutrition Examination Survey (NHANES) 2011-18. METHODS: This study included 8183 eligible nonpregnant participants aged ≥20 years from the NHANES 2011-18. MetS was defined as the presence of at least three of the following components: central obesity, reduced high-density lipoprotein cholesterol, elevated triglycerides, elevated blood pressure, and elevated fasting blood glucose. The prevalence of MetS was estimated taking into account the complex sampling. The time trend was evaluated using logistic regression. RESULTS: The total prevalence of MetS increased from 37.6% [95% confidence interval (CI): 34.0%-41.4%] in 2011-12 to 41.8% (95% CI: 38.1%-45.7%) in 2017-18 (P for trend = .028). Among the MetS components, the prevalence of elevated glucose increased from 48.9% (95% CI: 45.7%-52.5%) in 2011-12 to 64.7% (95% CI: 61.4%-67.9%) in 2017-18 (P for trend <.001). The prevalence of MetS in participants with low educational attainment increased from 44.4% (95% CI: 38.8%-50.1%) in 2011-12 to 55.0% (95% CI: 50.8%-59.1%) in 2017-18 (P for trend = .01). CONCLUSION: The prevalence of MetS increased during 2011-18, notably in participants with low educational attainment. Lifestyle modification is needed to prevent MetS and the associated risks of diabetes and cardiovascular disease. Key messages What is already known on this topic: Prevalence of metabolic syndrome is an index of the cardiometabolic health of a population. What this study adds: The prevalence of metabolic syndrome in US adults increased during 2011-18, notably in participants with low educational attainment. How this study might affect research, practice, or policy: Lifestyle modification is needed to prevent metabolic syndrome and the associated risks of diabetes and cardiovascular disease.

OBJECTIVE: In systemic lupus erythematosus (SLE), disease activity and glucocorticoid (GC) exposure are known to contribute to irreversible organ damage. We aimed to examine the association between GC exposure and organ damage occurrence. METHODS: We conducted a literature search (PubMed (Medline), Embase and Cochrane January 1966-October 2021). We identified original longitudinal observational studies reporting GC exposure as the proportion of users and/or GC use with dose information as well as the occurrence of new major organ damage as defined in the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Meta-regression analyses were performed. Reviews, case-reports and studies with <5 years of follow-up, <50 patients, different outcomes and special populations were excluded. RESULTS: We selected 49 articles including 16 224 patients, 14 755 (90.9%) female with a mean age and disease duration of 35.1 years and of 37.1 months. The mean follow-up time was 104.9 months. For individual damage items, the average daily GC dose was associated with the occurrence of overall cardiovascular events and with osteoporosis with fractures. A higher average cumulative dose adjusted (or not)/number of follow-up years and a higher proportion of patients on GC were associated with the occurrence of osteonecrosis. CONCLUSIONS: We confirm associations of GC use with three specific damage items. In treating patients with SLE, our aim should be to maximise the efficacy of GC and to minimise their harms.

BACKGROUND: A European League Against Rheumatism (EULAR) taskforce was convened to develop recommendations for lifestyle behaviours in rheumatic and musculoskeletal diseases (RMDs). This paper reviews the literature on the effects of physical exercise and body weight on disease-specific outcomes of people with RMDs. METHODS: Three systematic reviews were conducted to summarise evidence related to exercise and weight in seven RMDs: osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis, systemic sclerosis and gout. Systematic reviews and original studies were included if they assessed exercise or weight in one of the above RMDs, and reported results regarding disease-specific outcomes (eg, pain, function, joint damage). Systematic reviews were only included if published between 2013-2018. Search strategies were implemented in the Medline, Embase, Cochrane Library of systematic reviews and CENTRAL databases. RESULTS: 236 articles on exercise and 181 articles on weight were included. Exercise interventions resulted in improvements in outcomes such as pain and function across all the RMDs, although the size of the effect varied by RMD and intervention. Disease activity was not influenced by exercise, other than in axSpA. Increased body weight was associated with worse outcomes for the majority of RMDs and outcomes assessed. In general, study quality was moderate for the literature on exercise and body weight in RMDs, although there was large heterogeneity between studies. CONCLUSION: The current literature supports recommending exercise and the maintenance of a healthy body weight for people with RMDs.

Objectives Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous‐only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. Methods Genome‐wide meta‐analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single‐nucleotide polymorphism (SNP)–based heritability estimate (h 2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. Results We identified a novel genome‐wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10 −9 ), and key pathways that differentiate PsA from PsC, including NF‐κB signaling (adjusted P = 1.4 × 10 −45 ) and Wnt signaling (adjusted P = 9.5 × 10 −58 ). The heritability of PsA in this cohort was found to be moderate (h 2 SNP = 0.63), which was similar to the heritability of PsC (h 2 SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data. Conclusion Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

OBJECTIVE: The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow-up. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. RESULTS: Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244-566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80-6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05-3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43-20.39). CONCLUSION: Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five-year mortality.

OBJECTIVES: To examine associations between PsA and psoriasis vs lifestyle factors and comorbidities by triangulating observational and genetic evidence. METHODS: We analysed cross-sectional data from the UK Biobank (1836 PsA, 8995 psoriasis, 36 000 controls) to describe the association between psoriatic disease and lifestyle factors (including BMI and smoking) and 15 comorbidities [including diabetes and coronary artery disease (CAD)] using logistic models adjusted for age, sex and lifestyle factors. We applied bidirectional Mendelian randomization (MR) to genome-wide association data (3609 PsA and 7804 psoriasis cases, up to 1.2 million individuals for lifestyle factors and 757 601 for comorbidities) to examine causal direction, using the inverse-variance weighted method. RESULTS: BMI was cross-sectionally associated with risk of PsA (OR 1.31 per 5 kg/m2 increase; 95% CI 1.26, 1.37) and psoriasis (OR 1.23; 1.20, 1.26), with consistent MR estimates (PsA OR 1.38; 1.14, 1.67; psoriasis OR 1.36; 1.18, 1.58). In both designs, smoking was more strongly associated with psoriasis than PsA. PsA and psoriasis were cross-sectionally associated with diabetes (OR 1.35 and 1.39, respectively) and CAD (OR 1.56 and 1.38, respective). Genetically predicted glycated haemoglobin (surrogate for diabetes) increased PsA risk (OR 1.18 per 6.7 mmol/mol increase; 1.02, 1.36) but not psoriasis. Genetic liability to PsA (OR 1.05; 1.003, 1.09) and psoriasis (OR 1.03; 1.001, 1.06) were associated with increased risk of CAD. CONCLUSION: Observational and genetic evidence converge to suggest that BMI and glycaemic control are associated with increased psoriatic disease risk, while psoriatic disease is associated with increased CAD risk. Further research is needed to understand the mechanism of these associations.

OBJECTIVES: To estimate prevalence rates and identify baseline predictors of adverse events (AEs) over the first year of treatment in patients with RA starting MTX. METHODS: Data came from the UK Rheumatoid Arthritis Medication Study (RAMS), a prospective cohort of patients with RA starting MTX. This analysis included patients aged ≥18 years with physician diagnosed RA and symptom duration ≤2 years, who were commencing MTX for the first time. AEs were recorded by interviewing patients at 6- and 12-month follow-up visits. The period prevalence rates of AEs are reported for 0-6 months, 6-12 months and 0-12 months of follow-up. The associations between baseline characteristics and AEs were assessed using multivariable logistic regression. RESULTS: A total of 1069 patients were included in the analysis. Overall, 77.5% experienced at least one AE. The most commonly reported AEs were: gastrointestinal (42.0%), neurological (28.6%), mucocutaneous (26.0%), pulmonary (20.9%), elevated alanine transaminase (18.0%) and haematological AEs (5.6%). Factors associated with increased odds of AEs were: women vs men (gastrointestinal, mucocutaneous, neurological) and alcohol consumption (nausea, alopecia, mucocutaneous). Older age, higher estimated glomerular filtration rate and alcohol consumption were associated with less reporting of haematological AEs. CONCLUSIONS: AEs were common among patients over the first year of MTX, although most were not serious. Knowledge of the rates and factors associated with AE occurrence are valuable when communicating risks prior to commencing MTX. This can help patients make informed decisions whether to start MTX, potentially increasing adherence to treatment.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. METHODS: We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. RESULTS: Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. CONCLUSION: We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

OBJECTIVES: Osteoarthritis (OA) of the ankle joint is associated with life-long joint pain and disability if not appropriately managed. There is a dearth of research concerning ankle OA and the impact on those living with the condition. AIM: To explore the experiences of people living with painful OA ankle and their views about the non-surgical management of this condition. DESIGN: Qualitative design, using semi-structured interviews. PARTICIPANTS: Nine participants, recruited from an orthopaedic clinic at a UK hospital and the general population. All had a clinical and radiographic diagnosis of OA ankle. Interviews were digitally recorded and transcribed verbatim. Thematic analysis was undertaken to identify emerging themes. Ethical approval was obtained. RESULTS: Nine semi-structured interviews were undertaken. Eight participants were male, median age=55 years (IQR=42.5-64.5). Mechanism of onset was due to trauma (falls, repeated inversion injuries or road traffic collisions) (n=7), or the effects of haemophilia (n=2). The median duration of symptoms was 2 years (IQR=1.5-10). Data saturation was achieved. Four themes were identified: CONCLUSIONS: This is the first study to explore the experiences of people with symptomatic OA ankle. Our findings suggest that those with OA ankle suffer with severe pain, which has a substantial negative impact on a person's physical and mental wellbeing. The findings of this study may be used to inform future research.

Objective: We aimed to explore the frequency of self-reported flares and their association with preceding symptoms collected through a smartphone app by people with RA. Methods: We used data from the Remote Monitoring of RA study, in which patients tracked their daily symptoms and weekly flares on an app. We summarized the number of self-reported flare weeks. For each week preceding a flare question, we calculated three summary features for daily symptoms: mean, variability and slope. Mixed effects logistic regression models quantified associations between flare weeks and symptom summary features. Pain was used as an example symptom for multivariate modelling. Results: Twenty patients tracked their symptoms for a median of 81 days (interquartile range 80, 82). Fifteen of 20 participants reported at least one flare week, adding up to 54 flare weeks out of 198 participant weeks in total. Univariate mixed effects models showed that higher mean and steeper upward slopes in symptom scores in the week preceding the flare increased the likelihood of flare occurrence, but the association with variability was less strong. Multivariate modelling showed that for pain, mean scores and variability were associated with higher odds of flare, with odds ratios 1.83 (95% CI, 1.15, 2.97) and 3.12 (95% CI, 1.07, 9.13), respectively. Conclusion: Our study suggests that patient-reported flares are common and are associated with higher daily RA symptom scores in the preceding week. Enabling patients to collect daily symptom data on their smartphones might, ultimately, facilitate prediction and more timely management of imminent flares.

BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

ABSTRACT Background The U.S. opioid epidemic has led to similar concerns about prescribed opioids in the U.K. In new users, escalation to more potent and high-dose opioids may contribute to long-term use as well as opioid-related morbidity/mortality. The scale of such escalation is unclear for non-cancer pain. Additionally, physician prescribing behaviour has been described as a key driver of rising opioid prescriptions and long-term opioid use. No studies have investigated the extent to which regions, practices, prescribers, vary in opioid prescribing, whilst accounting for case-mix. Methods Using a retrospective cohort study we used U.K. primary-care electronic health records from Clinical Practice Research Datalink to: (i)describe prescribing trends between 2006-17 (ii)evaluate the transition of opioid dose and potency in the first 2-years from initial prescription (iii)quantify and identify risk factors for long- term opioid use (iv)quantify the variation of long-term use attributed to region, practice and prescriber, accounting for case-mix and chance variation. Adult patients with a new prescription of an opioid without cancer were included. Findings 1,968,742 new-users of opioids were identified. Rates of codeine use were highest, increasing five-fold from 2006-2017, reaching up to 2,456 prescriptions/10,000 people/year. Morphine, buprenorphine and oxycodone prescribing rates continued to rise steadily throughout the study period. Of those who started on high (100-200 Morphine Milligram Equivalents [MME]/day) or very high dose opioids (&gt;200 MME/day), 4.9% and 10.3% remained in the same or higher MME/day category throughout 2-years, respectively. Following opioid initiation, 15% became long-term opioid users. In the fully adjusted model, MME at initiation, older- age, social deprivation, fibromyalgia, rheumatological conditions, substance abuse, suicide/self-harm and gabapentinoid use were associated with the highest odds of long-term use. After adjustment for case-mix, the North-West, Yorkshire, South- West; 103 practices (25.6%) and 540 prescribers (3.5%) were associated with a significantly higher risk of long-term use. Interpretation Patients commenced on high MMEs were more likely to stay in the same state for a subsequent 2-years and were at increased risk of long-term use. In the first UK study evaluating long-term opioid prescribing with adjustment for patient-level characteristics, variation in regions and especially practices and prescribers were observed. Our findings support greater calls for action for reduction in practice and prescriber variation by promoting safe practice in opioid prescribing. Funding Versus Arthritis and National Institute for Health Research Research in Context Evidence before this study Drug dependence and deaths due to opioids have led to an opioid-overdose crisis in several countries globally including the US and Canada, and subsequent concerns about overprescribing in the UK. Physician prescribing behaviour has implicated as a key driver of rising opioid prescriptions and long-term opioid use however this needs to be assessed in the context of region, GP practice and individual patients. We searched Pubmed and Google Scholar between January 2005 and November 2019, with the terms “opioid” AND/OR “opiate”, “chronic pain” AND/OR “non-cancer pain”, and UK AND/OR England AND/OR “Great Britain” AND/OR “NHS”. We also reviewed relevant reports from Public Health England and other national bodies. The more recent trends for opioid prescribing have included all prescriptions including those for cancer pain, and those that include primary care UK prescription data for non-cancer indications are several years out of date. No studies evaluated how opioid dose and potency changes over time in individual patients after starting an opioid for the first time to assess escalation or tapering. National variation in opioid prescribing reported thus far has not accounted for patient case-mix. No studies have assessed the effect of the prescriber on opioid prescribing adjusting for regional, practice level variation and for individual characteristics. Added value of this study There has been a substantial overall increase in opioid-prescribing for non-cancer pain with clear drug-specific trends between 2006-17. To our knowledge, this is the first UK study that has evaluated the sequential transition on how dose/potency vary when a patient is first prescribed an opioid in primary care. Furthermore we report for the first time the effect of individual risk factors, UK regions, GP practice and prescriber (whilst considering these elements together) on long-term opioid use. Implications of all the available evidence Our study highlights the key subpopulations in a UK primary care setting at risk of developing long-term opioid use and the need for closer monitoring of at risk patients. Marked variation between region, practice and prescribers still exists after adjusting for case-mix warranting evidence-based harmonised opioid prescribing guidelines with clearer MME/day thresholds. On a practice level, guidance on regular review and dose reduction, as well as using prescriber and practice variations as a proxy for quality of care through audit and feedback, to highlight unwarranted variation to prescribers, could help drive safer prescribing.

AIM: to determine the impact of frailty on patient-reported outcomes following hip and knee arthroplasty. METHODS: we used linked primary and secondary care electronic health records. Frailty was assessed using the electronic frailty index (categorised: fit, mild, moderate, severe frailty). We determined the association between frailty category and post-operative Oxford hip/knee score (OHS/OKS) using Tobit regression. We calculated the proportion of patients in each frailty category who achieved the minimally important change (MIC) in OHS (≥8 points) and OKS (≥7 points) and the proportion who reported a successful outcome (hip/knee problems either 'much better' or 'a little better' following surgery). RESULTS: About 42,512 people who had a hip arthroplasty and 49,208 who had a knee arthroplasty contributed data. In a Tobit model adjusted for pre-operative OHS/OKS, age, sex and quintile of index of multiple deprivation, increasing frailty was associated with decreasing post-operative OHS and OKS, respectively, β-coefficient (95% CI) in severely frail versus fit, -6.97 (-7.44, -6.49) and - 5.88 (-6.28, -5.47). The proportion of people who achieved the MIC in OHS and OKS, respectively, decreased from 92 and 86% among fit individuals to 84 and 78% among those with severe frailty. Patient-reported success following hip and knee arthroplasty, respectively, decreased from 97 and 93% among fit individuals to 90 and 83% among those with severe frailty. CONCLUSION: frailty adversely impacts on patient-reported outcomes following hip and knee arthroplasty. However, even among those with severe frailty, the large majority achieved the MIC in OHS/OKS and reported a successful outcome.

BACKGROUND: Previous research has shown older adults experience dynamic changes in frailty status. This study aimed to determine the occurrence of sustained frailty remission and how remission is associated with falls risk. METHODS: Participants who contributed data to the analysis were in the English Longitudinal Study of Ageing from Waves 1 to 8 (2002-2017). Frailty was defined across waves using the frailty index and categorised into robust, pre-frail and frail. We classified participants who improved their frailty category from Wave 1 (2002) to Wave 2 (2004) and sustained/improved category again into Wave 3 (2006) and compared them with those who were either robust or frail across Waves 1-3. Cox proportional hazard modelling was used to determine the risk of incident falls reported at Waves 4-8, with results expressed as hazard ratios and 95% confidence intervals. RESULTS: Of 2,564 participants, 389 (15·2%) improved frailty category and sustained this during Waves 2-3, 1,489 (58·1%) remained robust and 686 (26·8%) remained frail during Waves 1-3. During the 10-year period (Waves 4-8), a total of 549 participants reported a fall. Compared with those who remained frail during Waves 1-3, those who with sustained frailty remission had a lower risk of future falls (HR 0·41; 95% CI = 0·36-0·45). CONCLUSIONS: Frailty remission is possible and can be sustained across 5 years. There is a lower risk of future falls in those who sustain frailty remission compared with those who remain frail.

OBJECTIVE: This report from the NORD-STAR (Nordic Rheumatic Diseases Strategy Trials and Registries) trial aimed to determine if obesity is associated with response to conventional and biological antirheumatic treatment in early rheumatoid arthritis (RA). METHODS: . All participants were randomised 1:1:1:1 to one of four treatment arms: active conventional treatment, certolizumab-pegol, abatacept and tocilizumab. Clinical and laboratory measurements were performed at baseline and at 8, 12, 24 and 48-week follow-up. The primary endpoint for this report was response to treatment based on Clinical Disease Activity Index (CDAI) and Simple Disease Activity Index (SDAI) remission and Disease Activity Score with 28 joints using C-reactive protein (DAS28-CRP) <2.6 stratified by BMI. RESULTS: Out of 793 people included in the present report, 161 (20%) had obesity at baseline. During follow-up, participants with baseline obesity had higher disease activity compared with those with lower BMI, despite having similar disease activity at baseline. In survival analyses, obesity was associated with a lower likelihood of achieving response to treatment during follow-up for up to 48 weeks (CDAI remission, HR 0.84, 95% CI 0.67 to 1.05; SDAI, HR 0.77, 95% CI 0.62 to 0.97; DAS28-CRP <2.6, HR 0.78, 95% CI 0.64 to 0.95). The effect of obesity on response to treatment was not influenced by the treatment arms. CONCLUSION: In people with untreated early RA followed up for up to 48 weeks, obesity was associated with a lower likelihood of good treatment response, irrespective of the type of randomised treatment received. TRIAL REGISTRATION NUMBER: NCT01491815.

OBJECTIVES: To characterize the incidence of clinically diagnosed Paget's disease of bone in the UK during 1999-2015 and to determine variations in the incidence of disease by age, sex, geography and level of deprivation. METHODS: Incident cases of Paget's disease occurring between 1999 and 2015 were identified from primary care records. Overall crude incidence and incidence stratified by age and sex was calculated each year from 1999 to 2015. Direct age- and sex-standardized incidence was also calculated. We used Poisson regression to look at variations in incidence by deprivation and UK region. RESULTS: A total of 3592 incident cases of Paget's disease were identified between 1999 and 2015. Incidence increased with age and at all ages was greater in men than women. In women and men, respectively, crude incidence increased from 0.037 and 0.074/10 000 population per year among those 45-49 years of age to 3.7 and 6.3/10 000 population per year among those ≥85 years. The overall standardized incidence decreased from 0.75/10 000 person-years in 1999 to 0.20/10 000 person-years in 2015. After adjustment for age and sex, incidence was >30% higher in the most- compared with least-deprived quintile of deprivation. There was evidence of geographic variation, with the highest incidence in the North West of England, which persisted after adjustment for age, sex and level of deprivation. CONCLUSION: The incidence of clinically diagnosed Paget's disease has continued to decrease since 1999. The reason for the decline in incidence remains unknown, although the rapidity of change points to an alteration in one or more environmental determinants.

OBJECTIVE: To quantify how well phase III randomised clinical trials in both SLE and lupus nephritis (LN) represents a real-world SLE cohort. METHODS: Literature reviews were performed of major published phase III SLE (n=12) and LN (n=6) clinical trials (ClinicalTrials.gov). Inclusion and exclusion criteria common across these trials were collated for non-renal SLE or LN trials, and applied to patients recruited to the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR) starting either biological or standard-of-care (SOC) therapies. RESULTS: We recruited 837 patients to the BILAG-BR from September 2010 to June 2018, starting either SOC (n=125, 15%) or a biological medication (n=712, 85%). Active LN, defined as a BILAG A in the renal domain occurred in 20% (n=166). Overall, 530 (63%) patients were ineligible to participate in non-renal SLE clinical trials and 72 (43%) patients with active LN would be ineligible for LN trials. The most common reasons for ineligibility from the non-renal lupus trials included active renal involvement (n=166, 20%) and low disease activity (n=114, 15%). For LN trials, the most common exclusion met was pre-existing renal impairment (n=15, 9%). Patients with fewer comorbidities were more likely to be eligible to participate in non-renal SLE trials. CONCLUSIONS: In this national register of patients with moderate-to-severe SLE, nearly two-thirds would not be eligible for recruitment to key SLE clinical trials nor would almost half of those with active LN. Eligibility criteria may excessively constrain enrolment and thus, how we can generalise trial results in a real-world setting.

OBJECTIVES: JIA is a heterogeneous group of rare autoimmune disorders characterized by chronic joint inflammation of unknown aetiology with onset under 16 years. Accurate estimates of disease rates help understand impacts on individuals and society, and provide evidence for health service planning and delivery. This study aimed to produce the first national estimates of incidence and prevalence by ethnic group using electronic health records. METHODS: Data from the Clinical Practice Research Datalink Aurum, a primary care electronic health record database in England, were used to estimate the incidence and prevalence of JIA by ethnic group amongst children and young people aged under 16 years between 2003 and 2018, with cases validated using Hospital Episode Statistics. χ2 was used to test the difference in proportions compared with the ethnic distribution of England. RESULTS: A total of 424 incident cases of JIA were identified, 389 validated using Hospital Episode Statistics records. Incidence of JIA was higher amongst those of white ethnic group (6.2 per 100 000 population) compared with mixed (3.0 per 100 000), Asian (2.7 per 100 000) and Black (2.9 per 100 000) communities. The ethnic group distribution of cases differed significantly compared with the general population (P < 0.0001). CONCLUSION: The incidence and prevalence of JIA differs between ethnic groups, and is different from the general population. This is likely to be due to a combination of genetic and equity factors. Further research to understand the underlying cause of these differences is important to enable targeted interventions and appropriate service provision.

BACKGROUND: There is a lack of data on SARS-CoV-2 vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data from adults with RMDs or CYP without RMDs. OBJECTIVES: To describe the safety of SARS-COV-2 vaccination in adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA). METHODS: We described patient characteristics, flares and adverse events (AEs) in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology COVAX registry. RESULTS: A total of 110 cases were reported to the registry. Thirty-six adolescent cases were reported from four countries, most with JIA (42%). Over half (56%) reported early reactogenic-like AEs. One mild polyarthralgia flare and one serious AE of special interest (malaise) were reported. No CYP reported SARS-CoV-2 infection postvaccination.Seventy-four adult JIA cases were reported from 11 countries. Almost two-thirds (62%) reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three female patients aged 20-30 years were diagnosed with SARS-CoV-2 postvaccination; all fully recovered. CONCLUSIONS: This is an important contribution to research on SARS-CoV-2 vaccine safety in adolescents with RMDs and adults with JIA. It is important to note the low frequency of disease flares, serious AEs and SARS-CoV-2 reinfection seen in both populations, although the dataset is limited by its size.

OBJECTIVE: To investigate the relationship between age and symptom duration at initial presentation to pediatric rheumatology for juvenile idiopathic arthritis (JIA). METHODS: In children and young people (CYP) enrolled in the Childhood Arthritis Prospective Study prior to March 2018, an association between age at presentation (&lt; 5, 5-11, and &gt; 11 yrs) and symptom duration was tested by multivariable linear regression. RESULTS: In 1577 CYP, 5- to 11-year-olds took 3.2 months longer and &gt; 11-year-olds 6.9 months longer to reach pediatric rheumatology than &lt; 5-year-olds. CONCLUSION: Adolescents take longer to reach pediatric rheumatology, potentially affecting their longer-term outcomes given the window of opportunity for JIA treatment.