Search

ObjectivesSome adults with rheumatic and musculoskeletal diseases (RMDs) are at increased risk of COVID-19-related death. Excluding post-COVID-19 multisystem inflammatory syndrome of children, children and young people (CYP) are overall less prone to severe COVID-19 and most experience a mild or asymptomatic course. However, it is unknown if CYP with RMDs are more likely to have more severe COVID-19. This analysis aims to describe outcomes among CYP with underlying RMDs with COVID-19.MethodsUsing the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database, we obtained data on CYP with RMDs who reported SARS-CoV-2 infection (presumptive or confirmed). Patient characteristics and illness severity were described, and factors associated with COVID-19 hospitalisation were investigated.Results607 CYP with RMDs ConclusionsThis is the most significant investigation to date of COVID-19 in CYP with RMDs. It is important to note that the majority of CYP were not hospitalised, although those with severe systemic RMDs and obesity were more likely to be hospitalised.

BackgroundThe COVID-19 pandemic disrupted healthcare and may have impacted ethnic inequalities in healthcare. We aimed to describe the impact of pandemic-related disruption on ethnic differences in clinical monitoring and hospital admissions for non-COVID conditions in England.MethodsWe conducted a cohort study using OpenSAFELY (2018-2022). We grouped ethnicity (exposure), into five categories: White, South Asian, Black, Other, Mixed. We used interrupted time-series regression to estimate ethnic differences in clinical monitoring frequency (e.g., blood pressure measurements) before and after 23rd March 2020. We used multivariable Cox regression to quantify ethnic differences in hospitalisations related to: diabetes, cardiovascular disease, respiratory disease, and mental health before and after 23rd March 2020.FindingsOf 14,930,356 adults in 2020 with known ethnicity (92% of sample): 86.6% were White, 7.3% Asian, 2.6% Black, 1.4% Mixed ethnicity, and 2.2% Other ethnicities. Clinical monitoring did not return to pre-pandemic levels for any ethnic group. Ethnic differences were apparent pre-pandemic, except for diabetes monitoring, and remained unchanged, except for blood pressure monitoring in those with mental health conditions where differences narrowed during the pandemic. For those of Black ethnicity, there were seven additional admissions for diabetic ketoacidosis per month during the pandemic, and relative ethnic differences narrowed during the pandemic compared to White. There was increased admissions for heart failure during the pandemic for all ethnic groups, though highest in White ethnicity. Relatively, ethnic differences narrowed for heart failure admission in those of Asian and Black ethnicity compared to White. For other outcomes the pandemic had minimal impact on ethnic differences.InterpretationOur study suggests ethnic differences in clinical monitoring and hospitalisations remained largely unchanged during the pandemic for most conditions. Key exceptions were hospitalisations for diabetic ketoacidosis and heart failure, which warrant further investigation to understand the causes.FundingLSHTM COVID-19 Response Grant (DONAT15912).Research in contextEvidence before this studyWe searched MEDLINE from inception to 7th September 2022, for articles published in English, including the title/abstract search terms (healthcare disruption OR indirect impact OR miss* diagnos* OR delayed diagnos* OR service disruption) AND (sars-cov-2 OR covid-19 OR pandemic OR lockdown) AND (ethnic*). Of the seven studies identified, two broadly investigated the indirect impacts of the pandemic on non-COVID outcomes and reported ethnic differences. However, these two only included data until January 2021 at the latest. Other studies investigated just one disease area such as dementia or diabetes and frequently did not have the power to investigate specific ethnic groups.Added value of this studyThis is one of the largest studies to describe how the pandemic impacted ethnic differences in clinical monitoring at primary care and hospital admissions for non-COVID conditions (across four disease areas: cardiovascular disease, diabetes mellitus, respiratory disease and mental health) in England. A study population of nearly 15 million people, allowed the examination of five ethnic groups, and data until April 2022 allowed the evaluation of impacts for a longer period than previous studies.We showed that clinical monitoring had still not returned to pre-pandemic levels even by April 2022. Ethnic differences in clinical monitoring were seen pre-pandemic, though not in diabetes measures, these differences were either not impacted or reduced during the pandemic. We also showed that there were ethnic differences in hospital admissions, for many outcomes the pandemic did not impact these differences but there were some exceptions, in particular for diabetic ketoacidosis admissions in those of Black ethnicity and heart failure admissions for those of Black and Asian ethnicities.Implications of all the available evidenceWe found that the pandemic reduced ethnic inequalities for some outcomes (in hospitalisations for diabetic ketoacidosis and heart failure). However, these were driven by greater absolute increases in admissions for black and asian groups (diabetic ketoacidosis) and white groups (heart failure), which warrant further investigation to understand the underlying causes.

Objective The incidence and prevalence of JIA was last estimated in the UK in 1994. Since then the disease has been reclassified, the specialty of paediatric rheumatology has evolved and there has been a significant shift in disease management with new advanced therapies. This study aimed to provide up-to-date national estimates of this disease. Methods Children and young people (CYP) with JIA were identified in the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases, which source data from the two most commonly used primary care electronic health record systems in the UK. These databases were combined and the cohort was identified (2000–18) using predefined code lists. Validation was performed through linkage to the England Hospital Episode Statistics. Annual incidence and prevalence rates were calculated and stratified by gender, age group and nation of the UK. Direct standardization to the UK population was performed and 5 year incidence rates were calculated between 2003 and 2018. Results The age-standardized incidence rate was 5.61 per 100 000 population. The age-standardized prevalence rate in 2018 was 43.5 per 100 000. Rates were higher in Scotland compared with England: incidence rate ratio 1.27 (95% CI 1.11, 1.46). The 5 year incidence rates did not change significantly over time. Conclusions This study has provided the first contemporaneous estimates of occurrence of JIA in the UK in 25 years. These data provide important estimates to inform resource allocation and health service development for management of JIA.

Introduction/Background It is estimated that juvenile idiopathic arthritis (JIA) persists into adulthood in at least one-third of patients, but it is unclear how frequently hospital services are used as young people move from paediatric to adult specialist services. This study aimed to describe characteristics related to continued specialist care in young people (YP) with JIA using electronic health records (EHR) in England. Description/Method YP with JIA were identified from primary care EHR (Clinical Practice Research Datalink GOLD and Aurum databases combined) between 2003 and 2018. JIA was identified if they had a Read code for JIA and either > =3 Hospital Episode Statistics (HES) outpatient specialist care (rheumatology/ophthalmology) appointments or a HES inpatient admission coded with JIA, prior to age 16. Further, cases needed to have linkage to HES data, registration at the same GP for >1 year beyond age 18. Cases were followed from the earliest of first Read code or first HES outpatient appointment until leaving their GP or end of 2018. Continuity of specialist care was categorised into 3 groups by age of last specialist care appointment: prior to 16 years, 16 to 17 years, and 18 years and beyond. YP were considered discharged from specialist care (a proxy for disease remission) if they had > =1 year between the last appointment and end of study follow-up. Multinomial logistic regression model assessed if any demographic or comorbidity variables were associated with continuing specialist care category. Discussion/Results Of 666 YP eligible, 427 (64%) received specialist care beyond age 18, 90 (13%) had their last recorded contact between 16-17 years and 149 (22%) did not continue after 16 years. Patients characteristics are described in Table 1. Of those continuing beyond 18, 35% (n = 153) were subsequently discharged by study end date. Of all those discharged, 32% had a missed appointment recorded after the last visit attended suggesting failure to attend. In the regression model, female gender and a childhood diagnosis of uveitis were associated with continuing specialist care beyond age 18 compared to those discharged before age 16; respective adjusted odds ratio (95% confidence intervals) 1.84 (1.25, 2.72) and 2.23 (1.14, 4.35). Key learning points/Conclusion Over two-third of patients with JIA continue to have hospital visits beyond age 18. Of those, however, approximately one-third were subsequently discharged or lost to follow up from adult specialist care. These data provide important information for YP with JIA and their families, as well as clinicians running, developing and planning young adult services in paediatric and adult rheumatology.

Background/Aims Juvenile idiopathic arthritis (JIA) is a chronic inflammatory condition affecting children and young people (CYP) with onset Methods CYP Results There were 1649 cases and 4748 controls included in this study. Most cases (1048, 64%) were female with median (interquartile range (IQR)) age at first JIA code 8.49 (4.20-12.05) years. Amongst cases, males were older at first JIA code, median (IQR) 9.80 (6.09-12.68) years, compared to females 7.55 (3.45-11.70) years. In both cases and controls, the proportion of CYP was highest in the most deprived quintile (IMD 1), 375/1649 (22.7%) and 1108/4738 (23.4%) respectively, and proportions remained similar in the remaining quintiles. There was no association identified between IMD quintile and occurrence of JIA, the multivariable odds ratio (95% CI) comparing most and least deprived groups was 0.98 (0.83-1.17). However, amongst cases there was an association between older age at diagnosis and higher SES [ß(95%CI) 0.15 years (0.01-0.29)] such that CYP in the IMD 5 quintile (highest SES) were on average 8 months older at their first JIA code compared to CYP in IMD 1. Conclusion This study found CYP from higher socio-economic groups appeared to be diagnosed at an older age than those from the least deprived backgrounds. Factors such as later presentation to healthcare after disease onset, delays in referrals to specialist care, delays in diagnosis by specialist care or differences in population demographics across IMD quantiles may all contribute to the older age of diagnosis in high SES group. Further research is required to explore these factors. Disclosure Y. Tan: None. R. Costello: None. K. Hyrich: None. J. Humphreys: None.

Glucocorticoids (GCs) are widely used to effectively treat inflammatory disease, however GCs have a number of recognised side effects. It has been shown that patients and clinicians view these side effects differently, with clinicians most concerned with serious side effects such as osteoporosis and diabetes. Consequently these side effects are well researched with clinical guidelines and recommendations. A side effect shown to be of particular concern to patients is weight gain, however this topic has not been well researched and consequently clinicians find it difficult to provide patients with accurate information about the potential of weight gain. The aim of this review is to provide an overview of GC use specifically in rheumatic disease, patient views on GC therapy and GC-induced weight gain. We will discuss the evidence including the extent and the impact of weight gain on the patient, and highlight areas that warrant further investigation.

Background First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) have a fourfold increased risk of developing RA. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire was developed to document symptoms in persons at risk of RA. The aims of this study were (1) to describe symptoms in a cohort of FDRs of patients with RA overall and stratified by seropositivity and elevated CRP and (2) to determine if patient characteristics were associated with symptoms suggestive of RA. Methods A cross-sectional study of FDRs of patients with RA, in the PREVeNT-RA study, who completed a study questionnaire, provided a blood sample measured for rheumatoid factor, anti-CCP and CRP and completed the SPARRA questionnaire. Moderate/severe symptoms and symmetrical, small and large joint pain were identified and described. Symptoms associated with both seropositivity and elevated CRP were considered suggestive of RA. Logistic regression was used to determine if symptoms suggestive of RA were associated with patient characteristics. Results Eight hundred seventy participants provided all data, 43 (5%) were seropositive and 122 (14%) had elevated CRP. The most frequently reported symptoms were sleep disturbances (20.3%) and joint pain (17.9%). Symmetrical and small joint pain were 11.3% and 12.8% higher, respectively, in those who were seropositive and 11.5% and 10.7% higher in those with elevated CRP. In the logistic regression model, seropositivity, older age and feeling depressed were associated with increased odds of small and symmetrical joint pain. Conclusions This is the first time the SPARRA questionnaire has been applied in FDRs of patients with RA and has demonstrated that the presence of symmetrical and small joint pain in this group may be useful in identifying people at higher risk of developing RA.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Background Elective total knee replacement (TKR) is a safe and cost-effective surgical procedure for treating severe knee osteoarthritis (OA). Although complications following surgery are rare, prediction tools could help identify those patients who are at particularly high risk who could then be targeted with preventative interventions. We aimed to develop a simple model to help inform treatment choices. Methods We trained and externally validated adverse event prediction models for patients with TKR using electronic health records (EHR) and claims data from the US (OPTUM, CCAE, MDCR, and MDCD) and general practice data in the UK (IQVIA Medical Research Database ([IMRD], incorporating data from The Health Improvement Network [THIN], a Cegedim database). The target population consisted of patients undergoing a primary TKR, aged ≥40 years and registered in any of the contributing data sources for ≥1 year before surgery. LASSO logistic regression models were developed for four adverse outcomes: post-operative (90-day) mortality, venous thromboembolism (VTE), readmission, and long-term (5-year) revision surgery. A second model was developed with a reduced feature set to increase interpretability and usability. Findings A total of 508,082 patients were included, with sample size per data source ranging from 1,853 to 158,549 patients. Overall, 90-day mortality, VTE, and readmission prevalence occurred in a range of 0.20%-0.32%, 1.7%-3.0% and 2.2%-4.8%, respectively. Five-year revision surgery was observed in 1.5%-3.1% of patients. The full model predicting 90-day mortality yielded AUROC of 0.78 when trained in OPTUM and yielded an AUROC of 0.70 when externally validated on THIN. We then developed a 12 variable model which achieved internal AUROC of 0.77 and external AUROC of 0.71 in THIN. The discriminative performances of the models predicting 90-day VTE, readmission, and 5-year revision were consistently poor across the datasets (AUROC Interpretation We developed and externally validated a simple prediction model based on sex, age, and 10 comorbidities that can identify patients at high risk of short-term mortality following TKR. Our model had a greater discriminative ability than the Charlson Comorbidity Index in predicting 90-day mortality. The 12-feature mortality model is easily implemented and the performance suggests it could be used to inform evidence based shared decision-making prior to surgery and for appropriate precautions to be taken for those at high risk. The other outcomes examined had low performance. Funding This activity under the European Health Data & Evidence Network (EHDEN) has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 806968. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The sponsor of the study did not have any involvement in the writing of the manuscript or the decision to submit it for publication. The research was supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). DPA is funded by a National Institute for Health Research Clinician Scientist award (CS-2013-13-012). TDS is funded by the Department of Health of the Generalitat de Catalunya under the Strategic Plan for Research and Innovation in Health (PERIS; SLT002/16/00308). The views expressed in this publication are those of the authors and not those of the NHS, the National Institute for Health Research or the Department of Health. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Key Points Question Is it possible to predict adverse events following total knee replacement? Findings Mortality was the only adverse event studied that we were able to predict with adequate performance. We produced a 12 variable prediction model for 90-day post-operative mortality that achieved an AUROC of 0.77 on internal test validation (Optum) and 0.71 when externally validated in THIN. The model also showed adequate calibration. Meaning Patients can now be presented with an accurate risk assessment for short term mortality such that they are well-informed before the decision for surgery is taken. Importance Total Knee Replacement is generally a safe, effective procedure that is performed on thousands of patients each year. However, a small number of those patients will experience adverse events. Due to the surgery’s elective nature, a well calibrated, high performing risk model could pre-emptively inform the patient and clinician decision making process and help to guide preventative treatment.

Objectives Patients with RA are frequently treated with glucocorticoids (GCs), but evidence is conflicting about whether GCs are associated with hypertension. The aim of this study was to determine whether GCs are associated with incident hypertension in patients with RA. Methods A retrospective cohort of patients with incident RA and without hypertension was identified from UK primary care electronic medical records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use, dose and cumulative dose, with a 3 month attribution window. Hypertension was identified through either: blood pressure measurements >140/90 mmHg, or antihypertensive prescriptions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards regression models were fitted to determine whether there was an association between GC use and incident hypertension. Results There were 17 760 patients in the cohort. A total of 7421 (42%) were prescribed GCs during follow-up. The incident rate of hypertension was 64.1 per 1000 person years (95% CI: 62.5, 65.7). The Cox proportional hazards model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio 1.17; 95% CI: 1.10, 1.24). When categorized by dose, only doses above 7.5 mg were significantly associated with hypertension. Cumulative dose did not indicate a clear pattern. Conclusion Recent GC use was associated with incident hypertension in patients with RA, in particular doses ≥7.5 mg were associated with hypertension. Clinicians need to consider cardiovascular risk when prescribing GCs, and ensure blood pressure is regularly monitored and treated where necessary.

Background Oral glucocorticoids (GC) are frequently prescribed to patients with rheumatoid arthritis (RA), however GC use is associated with several potential side effects. Hypertension is cited as a possible side effect, but few studies have specifically investigated GC-associated hypertension in patients with RA with conflicting results. The aim of this study was to determine whether GCs were associated with an increased risk of incident hypertension in a cohort of patients with RA. Methods A retrospective cohort of patients with incident RA and no hypertension at RA diagnosis were identified from UK primary care electronic health records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use and dose, categorised as: no use, >0-4.9 mg/day, 5-7.4 mg/day, 7.5-14.9 mg/day, ≥15mg/day. A 3-month risk attribution model was used where patients continued to remain at risk for 3 months after the end of prescriptions. Hypertension was identified if a patient had either: 1) 2 consecutive systolic blood pressure (BP) measurements >140mmHg within a year, 2) 2 consecutive diastolic BP measurements >90mmHg within a year or 3) antihypertensive prescriptions on at least two occasions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards (PH) regression models were fitted to determine if there was an association between GC use and hypertension. Results There were 17,760 patients with incident RA and no hypertension. The cohort had a mean age of 56.3 ± 12.7 years and were predominantly female (68%). 7,421 (42%) were prescribed GCs during follow-up. There were 6,243 cases of incident hypertension. The Cox PH model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio: 1.17 (95% CI 1.10 to 1.24)). When categorised by dose, only doses above 7.5mg were significantly associated with hypertension (Table 1). Conclusion In this large cohort of patients with RA and without hypertension, recent GC use was associated with incident hypertension. Doses ≥7.5mg were associated with hypertension while the association with lower doses was inconclusive. Clinicians need to consider cardiovascular risk when prescribing GCs and ensure BP is regularly monitored. Disclosures R.E. Costello None. M. Jani None. B.B. Yimer None. W.G. Dixon None.

Background Patients with rheumatoid arthritis (RA) have increased cardiovascular (CV) and mortality risk. Patients with RA are also frequently prescribed glucocorticoids (GCs) which have been associated with increased risk of mortality. In addition, for patients who have concomitant diabetes mellitus (DM), GCs are known to worsen glycaemic control and hence may further increase CV and mortality risk. This study aimed to understand the relationship between GCs, DM and mortality in patients with RA. Methods This was a retrospective cohort study of patients with incident RA identified from UK primary care electronic medical records. Patients with linkage to Office for National Statistics (ONS) for mortality data (N = 9085) were included. DM was identified through Read codes, prescriptions and blood tests, and GC use was identified through prescriptions. Mortality rate ratios (RR) and rate differences (RD) were calculated across the different exposure groups. Cox proportional hazards regression models were used to estimate interaction on the multiplicative and additive scales. Results In those without DM GC use had a 4.4-fold increased all-cause mortality RR (95% confidence interval (CI): 3.77 to 5.07) compared to non-use, whilst those with DM had a lower RR for GC use (2.99 (95% CI: 2.32, 3.87)). However, those with DM had a higher RD associated with GC use because of their higher baseline risk. In those with DM, GC use was associated with an additional 44.9 deaths/1000 person-years (pyrs) (95% CI: 32.9 to 56.8) compared to non-use, while in those without DM GC use was associated with an additional 34.4 deaths/1000 pyrs (95% CI: 30.1 to 38.7) compared to non-use, while in those without DM GC use was associated with an additional 36.2 deaths/1000 pyrs (95% CI: 31.6 to 40.8). A similar pattern was seen for CV mortality. The adjusted Cox proportional hazards model showed no evidence of multiplicative interaction, but additive interaction indicated a non-significant increased risk. For CV mortality there was no interaction on either scale. Conclusions GC use was associated with higher mortality rates in people with comorbid DM compared to people without DM, despite apparently reassuring similar relative risks. Clinicians need to be aware of the higher baseline risk in patients with DM, and consider this when prescribing GCs in patients with RA and comorbid DM.

Background There is uncertainty around whether to use unicompartmental knee replacement (UKR) or total knee replacement (TKR) for individuals with osteoarthritis confined to a single compartment of the knee. We aimed to emulate the design of the Total or Partial Knee Arthroplasty Trial (TOPKAT) using routinely collected data to assess whether the efficacy results reported in the trial translate into effectiveness in routine practice, and to assess comparative safety. Methods We did a population-based network study using data from four US and one UK health-care database, part of the Observational Health Data Sciences and Informatics network. The inclusion criteria were the same as those for TOPKAT; briefly, we identified patients aged at least 40 years with osteoarthritis who had undergone UKR or TKR and who had available data for at least one year prior to surgery. Patients were excluded if they had evidence of previous knee arthroplasty, knee fracture, knee surgery (except diagnostic), rheumatoid arthritis, infammatory arthropathies, or septic arthritis. Opioid use from 91–365 days after surgery, as a proxy for persistent pain, was assessed for all participants in all databases. Postoperative complications (ie, venous thromboembolism, infection, readmission, and mortality) were assessed over the 60 days after surgery and implant survival (as measured by revision procedures) was assessed over the 5 years after surgery. Outcomes were assessed in all databases, except for readmission, which was assessed in three of the databases, and mortality, which was assessed in two of the databases. Propensity score matched Cox proportional hazards models were fitted for each outcome. Calibrated hazard ratios (cHRs) were generated for each database to account for observed differences in control outcomes, and cHRs were then combined using meta-analysis. Findings 33 867 individuals who received UKR and 557 831 individuals who received TKR between Jan 1, 2005, and April 30, 2018, were eligible for matching. 32 379 with UKR and 250 377 with TKR were propensity score matched and informed the analyses. UKR was associated with a reduced risk of postoperative opioid use (cHR from meta-analysis 0·81, 95% CI 0·73–0·90) and a reduced risk of venous thromboembolism (0·62, 0·36–0·95), whereas no difference was seen for infection (0·85, 0·51–1·37) and readmission (0·79, 0·47–1·25). Evidence was insufficient to conclude whether there was a reduction in risk of mortality. UKR was also associated with an increased risk of revision (1·64, 1·40–1·94). Interpretation UKR was associated with a reduced risk of postoperative opioid use compared with TKR, which might indicate a reduced risk of persistent pain after surgery. UKR was associated with a lower risk of venous thromboembolism but an increased risk of revision compared with TKR. These findings can help to inform shared decision making for individuals eligible for knee replacement surgery.

Background First degree relatives (FDRs) of people with rheumatoid arthritis (RA) have a four-fold increased risk of developing RA. The Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire was developed to document symptoms in persons at risk of RA. Objectives To describe i) symptoms in a cohort of FDRs of patients with RA using the SPARRA questionnaire and (ii) the proportion of these symptoms in participants with detectable autoantibodies or elevated CRP. Methods The PRe-clinical EValuation of Novel Targets in RA (PREVeNT-RA) study is a cohort of FDRs of patients with RA, who are without inflammatory arthritis and aged ≥30 years at recruitment. Consented participants completed a study questionnaire and provided a blood sample for measurement of Rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP) and C-reactive protein (CRP). Those who agreed to future contact were asked to complete the SPARRA questionnaire. This questionnaire asks about a variety of joint symptoms, other symptoms and severity of joint pain in specific parts of the body, allowing identification of symmetrical, small and large joint pain. We identified subjects with moderate/severe symptoms and rheumatoid distribution (symmetrical, small and large joints). We also stratified these groups by 1) seropositivity (RF or anti-CCP positive) and 2) elevated CRP. Results By July 2018, 1866 participants had completed the study questionnaire and provided a blood sample. Of those 870 (47%) returned the SPARRA questionnaire and in this subgroup, 43 (5%) were seropositive and 122 (14%) had elevated CRP. The most frequently reported symptoms were sleep problems (20%), joint pain (18%) and fatigue (17%). The proportion with joint stiffness, symmetrical joint pain or small joint pain was higher in the seropositive and elevated CRP groups. This difference was statistically significant in those with elevated CRP, respective difference in proportions (95% CI) of small and symmetrical joint involvement were 10.7 (1.9 to 19.5) and 11.5 (3.2 to 19.8) (Table 1). Conclusion This is the first time the SPARRA questionnaire has been applied in FDRs of patients with RA. Some of the most prevalent symptoms e.g. sleep problems or fatigue, did not identify patterns suggestive of progression to RA. However, the distribution of joint involvement (symmetrical, small joint pain), was in keeping with RA features. This part of the questionnaire may be useful in identifying individuals most likely to develop RA. Disclosure of Interests Ruth Costello: None declared, Mohammad Haris: None declared, Jenny Humphreys: None declared, Jamie Sergeant: None declared, Fiona Stirling: None declared, Karim Raza: None declared, Dirkjan van Schaardenburg: None declared, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GlaxoSmithKline, Consultant for: AstraZeneca, Eli Lilly, GlaxoSmithKline, ILTOO Pharma, MedImmune, Merck Serono, Speakers bureau: GlaxoSmithKline, UCB Pharma

Purpose Treatments for rheumatoid arthritis (RA) over the last few decades have transformed the future outlook of the disease. Although patients with clinically apparent RA have a number of therapeutic options, all are associated with the risk of adverse events (AEs). Such therapeutics, facilitated by the identification of novel biomarkers and environmental and genetic factors to predict RA, may allow early detection, prompt treatment, and prevention before the future development of clinically apparent disease. Before choosing such treatments to make informed decisions in this context, however, accurate quantification of benefits and harms of such treatments is vital for participants without symptoms. This review summarizes the AEs reported in trials in preclinical or very early RA, the frequency and risk of primary AEs of concern associated with disease-modifying antirheumatic drugs (conventional, biologic, and targeted), glucocorticoids, and analgesia in clinically apparent RA. Also summarized is the evidence to date to support the quantification of benefit and harms incorporating patient preferences. Methods This analysis is a narrative review in which individual searches were performed in PubMed and EMBASE for each drug and topic outlined in the review. Findings Current therapies in RA can result in a considerable burden of AEs (serious and nonserious) depending on the individual's baseline risk. The absolute risk of serious AEs to treatments reported in individuals at risk of RA, undifferentiated, or very early inflammatory arthritis trials was low; however, nonserious AEs were not consistently reported. If such therapies prove effective at preventing the onset of RA in high-risk patients, incorporating patient preferences as well as robust quantification of benefits and harms to inform decisions is imperative. Patients' perceptions about treatment in this context may be risk averse or benefit driven. The risk of AEs that may not reverse after drug cessation, such as serious infection and malignancy, seem to be important AEs in such decision-making. Implications The impact of AEs in response to potentially preventative treatment is an important consideration for individuals at high risk of developing RA with minimal symptoms. Robust quantification of treatment effect given baseline risk versus the risks of developing all AEs (including those that may affect quality of life), while incorporating participants’ views, will be necessary for future informed decision-making.

Background:It remains unknown whether children and young people with rheumatic and musculoskeletal diseases (RMD) who acquire COVID-19 infection have a more severe COVID-19 course, due to either underlying disease or immunosuppressive treatments.Objectives:To describe outcomes among children and young people with underlying RMD who acquire COVID-19 infection.Methods:All children and young people Results:A total of 151 children and young people (age range 2-17 years; Table 1) have been reported to the database from 12 countries; mostly Spain (N=30), France (N=29), Israel (N=29), and Czechia (N=25). Most patients had a diagnosis of juvenile idiopathic arthritis (JIA; N=92; 61%). Other diagnoses were autoinflammatory syndrome (including TRAPS, CAPS, FMF; 12%), and systemic lupus erythematosus (4%). There were 14 (9%) hospitalisations and 1 (0.7%) death reported due to COVID-19. The most commonly reported symptoms were fever (46%), cough (34%), anosmia (19%), and headache (19%). Only 19 (13%) patients reported glucocorticoid use. DMARD therapy was used by 104 (69%) patients; 67 (44%) were on csDMARDs (methotrexate [N=54], antimalarials [N=7]), 45 (30%) on anti-TNF, 9 (6%) on IL-6 inhibitors, and 7 (5%) on IL-1 inhibitors. Among the 145 patients with hospitalisation data, patients on any DMARD therapy (cs/b/tsDMARDs) had similar odds for hospitalisation compared with those not on therapy, adjusted for age (odds ratio 0.7; 95% CI 0.2, 2.4).All PatientsN151GenderFemale94 (62%)Male56 (37%)Unknown1 (Age, yearsMedian (IQR)12 (8, 15)Range2 to 17Top Rheumatology DiagnosesJuvenile Idiopathic Arthritis (JIA)92 (61%)Polyarthritis50 (33%)Oligoarthritis31 (21%)Systemic11 (7%)Autoinflammatory syndrome (e.g.18 (12%)TRAPS, CAPS, FMF)6 (4%)Systemic Lupus ErythematosusComorbiditiesNone stated112 (74%)Obesity9 (6%)Ocular inflammationAsthma9 (6%)3 (2%)Required HospitalisationYes14 (9%)No131 (87%)Missing6 (4%)Top 5 Symptoms ReportedFever69 (46%)Cough51 (34%)Anosmia28 (19%)Headache28 (19%)Fatigue23 (15%)Deaths due to COVID-19Yes1 (Treatment at onset of COVID-19 infectionGlucocorticoids19 (13%)csDMARDs67 (44%)Methotrexate54 (36%)Antimalarials7 (5%)Mycophenolate5 (3%)bDMARDs64 (42%)Anti-TNF45 (30%)IL-69 (6%)IL-18 (5%)Any DMARD104 (69%)Conclusion:These initial data on outcomes of COVID-19 in paediatric RMDs are very reassuring, with less than 1 in 10 patients reporting hospitalisation. Due to the database design and inherent reporting bias, this is likely an overestimate, suggesting that overall outcomes among this population appear to be generally good, with mild infection. Increasing case reports to the database will allow further exploration of drug- and disease-specific outcomes.Disclosure of Interests:None declared.

Background:Oral glucocorticoids (GC) are frequently prescribed to patients with rheumatoid arthritis (RA), however GC use is associated with a number of potential side effects. Hypertension is cited as a possible side effect, but few studies have specifically investigated GC-associated hypertension in patients with RA with conflicting results.Objectives:The aim of this study was to determine whether GCs were associated with an increased risk of incident hypertension in a cohort of patients with RA.Methods:A retrospective cohort of patients with incident RA and no hypertension at RA diagnosis were identified from UK primary care electronic health records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use and dose, categorised as: no use, >0–4.9 mg/day, 5–7.4 mg/day, 7.5–14.9 mg/day, ≥15mg/day. A 3-month risk attribution model was used where patients continued to remain at risk for 3 months after the end of prescriptions. Hypertension was identified if a patient had either: 1) 2 consecutive systolic blood pressure (BP) measurements >140mmHg within a year, 2) 2 consecutive diastolic BP measurements >90mmHg within a year or 3) antihypertensive prescriptions on at least two occasions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards (PH) regression models were fitted to determine if there was an association between GC use and hypertension. Models were adjusted for baseline age, gender, baseline body mass index, baseline ever smoking, time-varying synthetic disease-modifying anti-rheumatic drug use, time-varying non-steroidal anti-inflammatory drug use and baseline Charlson comorbidity index.Results:There were 17,760 patients with incident RA and no hypertension. The cohort had a mean age of 56.3 ± 12.7 years and were predominantly female (68%). 7,421 (42%) were prescribed GCs during follow-up. There were 6,243 cases of incident hypertension over 97547 person years (pyrs) of follow-up, giving an incident rate of 64.1 per 1000 pyrs. Of those 1321 cases were in those exposed to GCs and 4922 were in those unexposed, giving incident rates of 87.6 per 1000 pyrs and 59.7 per 1000 pyrs, respectively. The adjusted Cox PH model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio: 1.17 (95% CI 1.10 to 1.24)). When categorised by dose, the adjusted model indicated only doses above 7.5mg were significantly associated with hypertension (Table 1).Table 1.Unadjusted and adjusted Cox proportional hazards regression model resultsUnadjustedHR (95% CI)Age and gender adjustedHR (95% CI)Fully adjusted* HR (95% CI)Recent GC use1.44(1.35 to 1.53)1.23(1.16 to 1.31)1.17(1.10 to 1.24)Recent GC doseNo GC useReferenceReferenceReference>0 – 4.9mg1.35(1.21 to 1.53)1.13(1.01 to 1.28)1.10(0.98 to 1.24)5mg – 7.4mg1.40(1.22 to 1.60)1.11(0.97 to 1.27)1.07(0.93 to 1.23)7.5mg – 14.9mg1.44(1.33 to 1.57)1.26(1.16 to 1.38)1.18(1.08 to 1.29)15mg and over1.60(1.40 to 1.84)1.45(1.27 to 1.66)1.36(1.18 to 1.56)* Adjusted for: Baseline age, gender, baseline body mass index, baseline ever smoking, synthetic disease-modifying anti-rheumatic drug use (time-varying), non-steroidal anti-inflammatory drug use (time-varying) and baseline Charlson comorbidity index.Conclusion:In this large cohort of patients with RA and without hypertension, recent GC use was associated with incident hypertension. In particular doses ≥7.5mg were associated with hypertension while the association with lower doses was inconclusive. Clinicians need to consider cardiovascular risk when prescribing GCs and ensure BP is regularly monitored.Disclosure of Interests:Ruth E Costello: None declared, Belay Birlie Yimer: None declared, Meghna Jani Speakers bureau: Grifols, William Dixon Consultant of: Bayer and Google

Background:Pneumococcal vaccinations are recommended for patients with rheumatoid arthritis (RA). There is evidence that pneumococcal vaccinations are less effective when administered after starting conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Vaccination guidelines have changed over time, since 1992 UK guidelines recommend pneumococcal vaccination for the immunocompromised, and in 2003 was expanded to all individual’s age ≥65 years. Guidelines from British Society of Rheumatology (2011) and EULAR (2019) advise to vaccinate prior to starting csDMARDs where possible. There is little evidence about whether these guidelines are being followed.Objectives:The aims of this study were to explore the timing of pneumococcal vaccination in patients with RA in relation to starting csDMARDs and examine whether this has changed over time.Methods:This was a cross-sectional study using UK electronic health records from primary care between 1st January 2000 and 31st December 2018. To be included in the study patients needed to 1) have a diagnosis of RA, 2) be prescribed csDMARDs up to 3 months prior to, or after RA diagnosis date and 3) have received a pneumococcal vaccination. Index date was considered the start of csDMARDs and vaccinations were required to be up to 5 years prior to the index date or after index date until leaving the practice, death or the end of the study period. For each patient it was determined if the first vaccination was prior to starting csDMARDs. For those vaccinated up to 3 years prior to, or up to 3 years after starting csDMARDs, the time between vaccination and starting csDMARDs in months was determined and this distribution was plotted in a bar chart. To explore how timing of vaccination has changed over time the proportion (with 95% confidence intervals (CI)) of people vaccinated prior to starting csDMARDs was plotted by year.Results:Of 21461 people with RA identified who were prescribed their first csDMARD on or after 1st January 2000, there were 8205 (38.2%) patients vaccinated and eligible to be included in the study. The cohort had a mean age 62 years, 66.4% were female. There were 2997 (36.5%) patients vaccinated prior to starting csDMARDs. Those vaccinated prior to starting csDMARDs were older, with 72% (n=2168) being aged 65 years or over vs 28% (n=1465) in those vaccinated after starting csDMARDs. 5358 (65.3%) were vaccinated up to 3 years prior to, or up to 3 years after starting csDMARDs. The distribution showed that the most frequent time of vaccination was in the 3 months after starting csDMARDs and the frequency was higher in the months after starting csDMARDs than in the months preceding (Figure 1). Of those vaccinated outside these times, 1000 (12.2%) were vaccinated >3 years prior and 1844 (22.5%) were vaccinated >3 years after starting csDMARDs. The proportion vaccinated prior to starting csDMARDs has increased over time from a minimum of 17.2% in 2001 to a maximum of 55.6% in 2016. The greatest increases were seen between 2003 and 2007 (Figure 2).Figure 1.Time between starting csDMARDs and pneumococcal vaccinationFigure 2.Proportion and 95% confidence interval of those vaccinated prior to starting csDMARDs by year.Conclusion:This study shows that timing of pneumococcal vaccination is improving with a trend towards increasing vaccination prior to starting csDMARDs and a high proportion of patients were vaccinated around the time of csDMARD initiation. However, just over a fifth (22.5%) were vaccinated more than 3 years after starting csDMARDs. Rheumatologists need to continue to work to raise awareness of the importance of vaccinations through better communications to patients and primary care physicians, to ensure best practice is being followed.Disclosure of Interests:Ruth E Costello: None declared, Jenny Humphreys: None declared, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, William Dixon Consultant of: Bayer and Google

Objectives To describe (1) the representativeness of (a) users of an online health community (HealthUnlocked.com (HU)) with rheumatoid arthritis (RA) and (b) paid members of an RA patient organisation, the National Rheumatoid Arthritis Society (NRAS), compared with the general RA population; and (2) the willingness of HU users with RA to participate in types of research (surveys, use of an app or activity tracker, and trials).Methods A pop-up survey was embedded on HU to determine the characteristics of users and their willingness to participate in research. An anonymous data set of NRAS member characteristics was provided by the NRAS (N=2044). To represent the general RA population, characteristics of people with RA were identified from the Clinical Practice Research Datalink (CPRD) (N=20 594). Cross-sectional comparisons were made across the three groups.Results Compared with CPRD, HU respondents (n=615) were significantly younger (49% aged below 55 years compared with 23% of CPRD patients), significantly more deprived (21% in the most deprived Townsend quintile compared with 12% of CPRD patients) and had more recent disease, with 62% diagnosed between 2010 and 2016 compared with 37% of CPRD patients. NRAS members were more similar to the CPRD, but significantly under-represented those aged 75 years or over and over-represented those aged 55–75 years compared with the CPRD. High proportions of HU users were willing to participate in future research of all types.Conclusions NRAS members were broadly representative of the general RA population. HU users were younger, more deprived and more recently diagnosed. HU users were willing to participate in most types of research.

Background Glucocorticoids (GC) are widely used to treat rheumatoid arthritis (RA), however they are known to have risks associated with them. It has been shown that GCs increase the risk of diabetes mellitus (DM). A few studies have investigated the long-term effects of GC use on outcomes in DM, but not in RA specifically. As people with RA already have increased risk of cardiovascular (CV) disease, the additional burden of DM and GCs may be important. If the effect of GCs was dependent on DM we would say there is effect modification and this can be on the additive scale, corresponding to variation in the absolute treatment effect, e.g. the risk difference (RD), across DM status, or the multiplicative scale, corresponding to variation in the relative treatment effect e.g. the rate ratio (RR).1 Objectives To examine in patients with RA 1) whether all-cause and CV mortality rates differ by GC and DM status, and 2) whether DM modifies the relationship between GC and all-cause and CV mortality on multiplicative and additive scales. Methods Patients with RA and linkage to mortality data were identified from the Clinical Practice Research Datalink (n=9085), a database of primary care electronic medical records in the UK. RR and RD for ever GC use were calculated by DM status. Cox proportional hazards (PH) regression models were fitted with an interaction term for DM and use of GC to assess multiplicative interaction. Additive interaction was measured with the Relative Excess Risk due to Interaction (RERI)2 where a value different from zero indicates a difference in the absolute effect of treatment. Results Those with DM and ever treated with GCs had a 3-fold increased all-cause mortality RR (95% CI: 2.27, 4.09) whilst those without DM had a slightly higher RR (3.46 (95% CI: 2.95, 4.07)). However those with DM had a higher RD: 36.46 deaths per 1000 patient years (pyrs) (95% CI: 27.5, 45.41) compared to those without DM: RD 22.83 deaths per 1000 pyrs (95% CI: 19.83, 25.82) because of higher baseline mortality rates. A similar pattern was seen for CV mortality. The adjusted Cox PH model for all-cause mortality showed no evidence of multiplicative interaction, but there was significant additive interaction (RERI 0.86 (95% CI: 0.18, 1.54)). For CV mortality there was no interaction on either scale. Conclusions Methodologically, this study showed assessing interaction on the additive and multiplicative scales can lead to different conclusions and should be considered carefully. In this study significant interaction was seen on additive scale but not on the multiplicative scale due to higher baseline rates in patients with DM. Clinically, this study provides some evidence that long-term GC therapy may be particularly harmful in patients with RA and DM. References [1] VanderWeele TJ, Knol MJ. A tutorial on interaction. Epidemiologic Methods2014;3(1):33–72. [2] Li R, Chambless L. Test for additive interaction in proportional hazards models. Annals of epidemiology2007Mar;17(3):227–236. Disclosure of Interest None declared

Background Studies requiring large numbers of participants usually recruit from hospital clinics or general practice registers. These recruitment methods are expensive, time consuming and often fail to reach recruitment targets. One method to overcome these limitations is to recruit patients directly through the internet or patient organisations. However it is not known how willing people would be to take part in different types of research and how representative participants would be of the target population. Objectives To describe: 1) the willingness of users of an online health community (HealthUnlocked.com (HU)) with rheumatoid arthritis (RA) to participate in research, 2) the representativeness of HU users and patient organisation members (National Rheumatoid Arthritis Society (NRAS)) with RA compared to the general RA population identified from a UK primary care research database (the Clinical Practice Research Datalink (CPRD)). Methods A pop-up survey was embedded on HU to determine users’ willingness to participate in different types of research, demographics (age, gender, employment, postcode and ethnicity) and disease duration. NRAS provided a dataset of their members’ demographics and disease characteristics. People with RA were identified from the CPRD, to represent the general RA population. Willingness and characteristics of those willing to take part in research was tabulated. The characteristics of HU users and NRAS members were compared to the characteristics of the RA cohort from CPRD. Results The HU survey was live for 74 days between May and August 2016 and had 1 00 112 pop-ups. 2647 people clicked on the pop-up, 900 people agreed to take part, 750 respondents had RA, of whom 135 did not provide age and gender resulting in 615 responses available for analysis. Over 80% of users were willing to complete questionnaires of different lengths, from a single questionnaire taking up to 1 min to complete, to multiple questionnaires over a number of months. 74% were willing to wear an activity tracker and 63% to use an app. Just over half (53%) were willing to take part in trials that involved visits to clinics (figure 1). Younger users were more willing to take part in all types of research, with 2% to 17% difference between those aged less than 65 years and those 65 years or over. Compared to those 65 years or over, 2% more of those aged less than 65 years were willing to complete multiple questionnaires over a number of months and 17% more were willing to provide information via an app. HU users were younger than NRAS and the general RA population (Age Conclusions Participants surveyed online show high rates of willingness to participate in research studies. While broadly representative of the general RA, they were younger and more recently diagnosed and these population differences should be considered during study design. Disclosure of Interest None declared

We thank Drs Kremer and Weinblatt for their interest in our study.1 We agree and acknowledge that lack of biopsies and detailed histology is a limitation of our study.2 Unfortunately good quality data on liver biopsies and ultrasound scans were not available in this retrospective observational study and would not have been systematically performed in all patients, necessitating the use of serum liver function tests (LFTs). However this limitation is balanced against our ability to study a rare outcome in a large number of people. The strengths of observational data are that they reflect ‘real-life’ usage versus a carefully monitored research cohort, and this …

Objectives To identify the side effects most important to glucocorticoid (GC) users through a survey of a UK online health community (Healthunlocked.com). Design Online cross-sectional survey. Setting Participants were recruited through Healthunlocked.com, an online social network for health. Participants Adults who were currently taking GCs, or had taken GCs in the past month. Method Responders scored the importance of listed side effects from 1 to 10, with 10 being of high importance to them. For each side effect, histograms were plotted, and the median rating and IQR were determined. Side effects were ranked by median ranking (largest to smallest) and then IQR (smallest to largest). The scores were categorised as low (scores 1–3), medium (scores 4–7) and high (scores 8–10) importance. Results 604 responders completed the survey. Histograms of side effect scores showed a skew towards high importance for weight gain, a U-shaped distribution for cardiovascular disease (CVD), diabetes, eye disease and infections, and a skew towards low importance for acne. When ranked, the side effect of most importance to responders was weight gain (median score=9, IQR 6–10) followed by insomnia and moon face with equal median score (8) and IQR (5–10). Three serious side effects, CVD, diabetes and infections, were ranked of lower importance overall but had wide ranging scores (median score=8, IQR 1–10). Conclusions The three most highly rated side effects were not clinically serious but remained important to patients, perhaps reflecting their impact on quality of life and high prevalence. This should be taken into consideration when discussing treatment options and planning future GC safety studies.

Background Participation in online health communities (OHCs) is a popular trend in the United Kingdom. However, so far, no evidence exists to indicate an association between participation in OHCs and improved health outcomes. Objective This study aimed to (1) determine changes in patient activation over 3 months in new users of an OHC, (2) describe patterns of engagement with an OHC, (3) examine whether patients’ characteristics at baseline were associated with subsequent patterns of engagement, and (4) determine if patterns of engagement during the 3 months were associated with changes in patient activation, health care utilization, and health status. Methods Active new OHC users on HealthUnlocked (HU) were surveyed to measure demographics, levels of patient activation (describing a person’s confidence in managing their own health; scale 0-100 with 4 categories), health care utilization, and health status using a Web-based survey at baseline and 3 months. Patient activation at baseline and 3 months was compared (aim 1). Alongside, for a sample of HU users and survey responders, daily OHC website usage data were automatically captured. This was used to identify clusters of engagement with HU (aim 2). For survey responders, baseline characteristics, patient activation, health care utilization, and health status were compared at baseline and 3 months, overall, and between engagement clusters using t tests and chi-square tests (aims 3 and 4). Results In 329 people who completed both surveys, baseline activation was most frequently level 3, described as taking action but still lacking confidence. At follow-up, a change of 2.6 points was seen, with the greatest change seen in those at lowest baseline activation levels. In addition, 4 clusters of engagement were identified: low, medium, high, and very high, who were active on HU for a mean of 4, 12, 29, and 59 days, respectively. Survey responders were more commonly high or very high engagers. Baseline activation was highest in low and very high engagers. Overall activation increased over time in all engagement groups. Very high engagers had the greatest improvement in activation (5 points), although the average change was not above what is considered clinically meaningful for any group. Fewer accident and emergency visits were seen at follow-up in those with higher engagement, although this trend was not seen for other health care utilization measures. There was no change in health status at 3 months. Conclusions This observational study provides some insight into how patterns of engagement with OHCs are associated with changes in patient activation, health care utilization, and health status. Over 3 months, overall, the change in activation was not clinically significant, and there were some indications that OHCs may be of benefit to particular groups. However, the study limitations prevent firm conclusions about causal relationships.

Previous studies of glucocorticoid (GC) therapy and mortality have had inconsistent results and have not considered possible perimortal bias—a type of protopathic bias where illness in the latter stages of life influences GC exposure, and might affect the observed relationship between GC use and death. This study aimed to investigate all-cause and cause-specific mortality in association with GC therapy in patients with rheumatoid arthritis (RA), and explore possible perimortal bias. A retrospective cohort study using the primary care electronic medical records. Oral GC exposure was identified from prescriptions. Mortality data were obtained from the UK Office for National Statistics. Multivariable Cox proportional hazards regression models assessed the association between GC use models and death. Several methods to explore perimortal bias were examined. The cohort included 16,762 patients. For ever GC use there was an adjusted hazard ratio for all-cause mortality of 1.97 (95 % CI 1.81–2.15). Current GC dose of below 5 mg per day (prednisolone equivalent dose) was not associated with an increased risk of death, but a dose–response association was seen for higher dose categories. The association between ever GC use and all-cause mortality was partly explained by perimortal bias. GC therapy was associated with an increased risk of mortality for all specific causes considered, albeit to a lesser extent for cardiovascular causes. GC use was associated with an increased risk of death in RA, at least partially explained by perimortal bias. Importantly, GC doses below 5 mg were not associated with an increased risk of death. Electronic supplementary material The online version of this article (doi:10.1007/s10654-016-0167-1) contains supplementary material, which is available to authorized users.

Introduction Guidelines for the management of rheumatoid arthritis (RA) recommend using influenza and pneumococcal vaccinations to mitigate infection risk. The level of adherence to these guidelines is not well known in the UK. The aims of this study were to describe the uptake of influenza and pneumococcal vaccinations in patients with RA in the UK, to compare the characteristics of those vaccinated to those not vaccinated and to compare vaccination rates across regions of the UK. Methods A retrospective cohort study of adults diagnosed with incident RA and treated with non-biologic immunosuppressive therapy, using data from a large primary care database. For the influenza vaccination, patients were considered unvaccinated on 1st September each year and upon vaccination their status changed to vaccinated. For pneumococcal vaccination, patients were considered vaccinated after their first vaccination until the end of follow-up. Patients were stratified by age 65 at the start of follow-up, given differences in vaccination guidelines for the general population. Results Overall (N = 15,724), 80% patients received at least one influenza vaccination, and 50% patients received a pneumococcal vaccination, during follow-up (mean 5.3 years). Of those aged below 65 years (N = 9,969), 73% patients had received at least one influenza vaccination, and 43% patients received at least one pneumococcal vaccination. Of those aged over 65 years (N = 5,755), 91% patients received at least one influenza vaccination, and 61% patients had received at least one pneumococcal vaccination. Those vaccinated were older, had more comorbidity and visited the GP more often. Regional differences in vaccination rates were seen with the highest rates in Northern Ireland, and the lowest rates in London. Conclusions One in five patients received no influenza vaccinations and one in two patients received no pneumonia vaccine over five years of follow-up. There remains significant scope to improve uptake of vaccinations in patients with RA.

Background The guidelines for the management of rheumatoid arthritis (RA) recommend an annual influenza vaccine and a pneumonia vaccination (EULAR, 2011), prior to starting disease-modifying anti-rheumatic drug (DMARD) therapy. The proportion of patients with RA in the UK receiving these vaccinations, and the timing of vaccinations in relation to starting DMARD therapy, is not clear. Objectives To measure the extent to which patients with RA are vaccinated in the UK, and to determine the timing of the vaccinations in relation to starting DMARD therapy. Methods This was a retrospective cohort study using data from the Clinical Practice Research Datalink (CPRD). An inception cohort of patients, aged 18 years and over, who were diagnosed with RA and were prescribed DMARD therapy during follow-up (1st January 2000 – 31st December 2013) were identified. Vaccination status was considered as follows: 1) Influenza: The influenza season was estimated to start on 1st September each year and all patients were considered unvaccinated at this point. Patients were considered vaccinated if they received an influenza vaccine between 1st September and 31st March the following year. 2) Pneumonia: Following vaccination patients were considered vaccinated for the rest of follow-up. For both influenza and pneumonia vaccines, descriptive statistics show 1) the proportion having at least one vaccination, 2) the observed and expected use and 3) the proportion of first vaccinations occurring prior to DMARD therapy initiation. Patients were divided into those above or below 65 at the start of follow-up, given differences in vaccination guidelines for the general population. Results There were 17,877 patients with RA identified who were treated with DMARD therapy during follow-up. Age below 65 years (N=11391): 8299 (73%) patients had received at least one influenza vaccination, of whom 2968 (36%) were vaccinated prior to starting DMARD therapy. On average 64% of expected vaccinations were received. Of those expected to have up to 5 vaccinations, 20% - 30% received all expected vaccinations. There were 4960 (44%) patients who had received at least one pneumonia vaccination, of whom 1269 (26%) were vaccinated prior to starting DMARD therapy. Age 65 years and over (N=6486): 5851 (90%) patients received at least one influenza vaccination, of whom 4549 (78%) were vaccinated prior to starting DMARD therapy. On average 86% of expected vaccinations were received. Of those expected to have up to 5 vaccinations, 55%>75% received all expected vaccinations. There were 4026 (62%) patients who received at least one pneumonia vaccination, of whom 2498 (62%) received a vaccination prior to starting DMARD therapy ([Table 1][1]). ![Figure][2] Conclusions Overall uptake of vaccinations for influenza was greater than uptake of vaccinations for pneumonia. Patient's aged below 65 years were vaccinated less than those who were aged 65 years or over. Many patients were not vaccinated before initiating DMARD therapy, especially if they were younger. Disclosure of Interest None declared [1]: #F1 [2]: pending:yes

An accurate assessment of the safety or effectiveness of drugs in pharmaco-epidemiological studies requires defining an etiologically correct time-varying exposure model, which specifies how previous drug use affects the outcome of interest. To address this issue, we develop, and validate in simulations, a new approach for flexible modeling of the cumulative effects of time-varying exposures on repeated measures of a continuous response variable, such as a quantitative surrogate outcome, or a biomarker. Specifically, we extend the linear mixed effects modeling to estimate how past and recent drug exposure affects the way individual values of the outcome change throughout the follow-up. To account for the dosage, duration and timing of past exposures, we rely on a flexible weighted cumulative exposure methodology to model the cumulative effects of past drug use, as the weighted sum of past doses. Weights, modeled with unpenalized cubic regression B-splines, reflect the relative importance of doses taken at different times in the past. In simulations, we evaluate the performance of the model under different assumptions concerning (i) the shape of the weight function, (ii) the sample size, (iii) the number of the longitudinal observations and (iv) the intra-individual variance. Results demonstrate the accuracy of our estimates of the weight function and of the between- and within-patients variances, and good correlation between the observed and predicted longitudinal changes in the outcome. We then apply the proposed method to re-assess the association between time-varying glucocorticoid exposure and weight gain in people living with rheumatoid arthritis.