OpenSAFELY: The impact of COVID-19 on azathioprine, leflunomide and methotrexate monitoring, and factors associated with change in monitoring rate.

AIMS: The COVID-19 pandemic created unprecedented pressure on healthcare services. This study investigates whether disease-modifying antirheumatic drug (DMARD) safety monitoring was affected during the COVID-19 pandemic. METHODS: A population-based cohort study was conducted using the OpenSAFELY platform to access electronic health record data from 24.2 million patients registered at general practices using TPP's SystmOne software. Patients were included for further analysis if prescribed azathioprine, leflunomide or methotrexate between November 2019 and July 2022. Outcomes were assessed as monthly trends and variation between various sociodemographic and clinical groups for adherence with standard safety monitoring recommendations. RESULTS: An acute increase in the rate of missed monitoring occurred across the study population (+12.4 percentage points) when lockdown measures were implemented in March 2020. This increase was more pronounced for some patient groups (70-79 year-olds: +13.7 percentage points; females: +12.8 percentage points), regions (North West: +17.0 percentage points), medications (leflunomide: +20.7 percentage points) and monitoring tests (blood pressure: +24.5 percentage points). Missed monitoring rates decreased substantially for all groups by July 2022. Consistent differences were observed in overall missed monitoring rates between several groups throughout the study. CONCLUSION: DMARD monitoring rates temporarily deteriorated during the COVID-19 pandemic. Deterioration coincided with the onset of lockdown measures, with monitoring rates recovering rapidly as lockdown measures were eased. Differences observed in monitoring rates between medications, tests, regions and patient groups highlight opportunities to tackle potential inequalities in the provision or uptake of monitoring services. Further research should evaluate the causes of the differences identified between groups.

No Waning of Pneumococcal Vaccine Responses over Time in People with Inflammatory Arthritis: Findings from a Single Centre Cohort.

BACKGROUND: Vaccination against pneumococcus reduces the risk of infective events, hospitalisation, and death in individual with inflammatory arthritis, particularly in those on immunomodulating therapy who are at risk of worse outcomes from pneumococcal disease. The objective of this study was to investigate the serological protection following vaccination against pneumococcal serovars over time. Methods: This was a single centre, retrospective cohort study of individuals with rheumatoid arthritis, psoriatic arthritis, or axial spondylarthritis who had previously received the PPSV23 polysaccharide pneumococcal vaccine (Pneumovax). Data were retrieved between January 2021 to August 2023. Dates of previous pneumococcal vaccination were identified using linked primary care records. Serum serotype levels were collected. The primary outcome was serological response defined as a titre ≥0.35 mcg/mL in at least five from a total of 12 evaluated pneumococcal serovars, examined using a Luminex platform. Multivariate logistic regression models adjusting for age, gender, ethnicity, co-morbidities, and the use of prednisolone, conventional synthetic and biological DMARDs were used to determine the odds of a sustained serological response according to time categorised into ≤5 years, 5-10 years, and ≥10 years since vaccination. Results: Serological response was measured in 296 individuals with inflammatory arthritis, with rheumatoid arthritis the most common diagnosis (74% of patients). The median time between pneumococcal vaccine administration and serological assessment was 6 years (interquartile range 2.4 to 9.9). A positive serological response to at least 5 serovars was present in 195/296 (66%) of patients. Time since vaccination did not significantly associate with serological protection compared with those vaccinated <5 years, the adjusted ORs of vaccine response was 1.15 (95% CI 0.64 to 2.07) in those 5-10 years and 1.26 (95% CI: 0.64 to 2.48) in those vaccinated over 10 years ago. No individual variable from the multivariate model reached statistical significance as an independent predictor of vaccine response, although steroid use at the time of vaccine had a consistent detrimental impact on serological immunity. Conclusions: We demonstrated that antibody titres following vaccination against pneumococcal serovars do not appear to wane over time. It appears more critical to focus on maximising the initial vaccine response, which is known to be diminished in this patient population.

Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA. METHODS: We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool. RESULTS: Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo. CONCLUSION: Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.

A Systematic Review and Meta-Analysis of Anti-Rheumatic Drugs and Pneumococcal Vaccine Immunogenicity in Inflammatory Arthritis.

BACKGROUND: Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute for Health and Care Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our objective was to compare the chance of a seroconversion following vaccination against pneumococcus in patients with inflammatory arthritis to that in the general population, as well as to compare the chance of seroconversion across different targeted therapies. METHODS: We searched MEDLINE, Embase and the Cochrane Library databases from inception until 20 June 2023. We included randomized controlled trials and observational studies. Aggregate data were used to undertake a pairwise meta-analysis. Our primary outcome of interest was vaccine seroconversion. We accepted the definition of serological response reported by the authors of each study. RESULTS: Twenty studies were identified in the systematic review (2807 patients) with ten reporting sufficient data to be included in the meta-analysis (1443 patients). The chance of seroconversion in patients receiving targeted therapies, relative to the general population, was 0.61 (95% CI 0.35 to 1.08). The reduced odds of response were skewed strongly by the effects of abatacept and rituximab with no difference between patients on TNF inhibitors (TNFis) or IL-6 inhibition and healthy controls. Within different inflammatory arthritis populations the findings remained consistent, with rituximab having the strongest negative impact on vaccine response. TNF inhibition monotherapy was associated with a greater chance of vaccine response compared with methotrexate (2.25 (95% CI 1.28 to 3.96)). JAK inhibitor (JAKi) studies were few in number and did not present comparable vaccine response endpoints to include in the meta-analysis. The information available does not suggest any significant detrimental effects of JAKi on vaccine response. CONCLUSION: This updated meta-analysis confirms that, for most patients with inflammatory arthritis, pneumococcal vaccine can be administered with confidence and that it will achieve comparable seroconversion rates to the healthy population. Patients on rituximab were the group least likely to achieve a response and further research is needed to explore the value of multiple-course pneumococcal vaccination schedules in this population.

Implementing treat-to-target urate-lowering therapy during hospitalisations for gout flares.

OBJECTIVES: To evaluate a strategy designed to optimise care and increase uptake of urate-lowering therapy (ULT) during hospitalisations for gout flares. METHODS: We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment, and re-hospitalisation rates, were compared between patients hospitalised for flares in the 12 months post-implementation and a retrospective cohort of hospitalised patients from 12 months pre-implementation. RESULTS: 119 and 108 patients, respectively, were hospitalised for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n = 94 and n = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio (aOR) 11.5; 95% confidence interval (CI) 4.36-30.5; p < 0.001). After implementation, more patients achieved a serum urate ≤360 micromol/L within 6 months of discharge (10.6% pre-implementation vs. 26.8% post-implementation; aOR 3.04; 95% CI 1.36-6.78; p = 0.007). The proportion of patients re-hospitalised for flares was 14.9% pre-implementation vs. 9.3% post-implementation (aOR 0.53, 95% CI 0.22 to 1.32; p = 0.18). CONCLUSION: Over 90% of patients were initiated on ULT after implementing a strategy to optimise hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalisations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalised gout patients to achieve urate targets, closer primary-secondary care integration is still needed.

Occupational impacts of early inflammatory arthritis: results from the National Early Inflammatory Arthritis Audit.

OBJECTIVES: Inflammatory arthritis (IA) causes significant work disability. Studies frequently fail to report important contextual information such as employment type. Our objective was to explore work participation, by gender and occupation type in early IA. METHODS: Data are from the National Early Inflammatory Arthritis Audit between 2018 and 2020. At diagnosis, clinicians collected information on demographics, IA disease activity and working status. Participants completed patient-reported outcomes at baseline, 3- and 12-months, including occupation and Work Productivity Activity Impairment (WPAI). Descriptive analyses of work participation and WPAI scores by occupational class at all timepoints were performed. Regression models examined associations between WPAI score and occupation. FINDINGS: 12 473 people received a diagnosis of IA and reported employment status, amongst whom 5,999 (47%) were in paid-work at least 20-h/week. At diagnosis, the working cohort had statistically significant lower measures of disease activity (p< 0.001). Occupation data were available for 3,694 individuals. At diagnosis, 2,793 completed a WPAI; 200 (7.2%) had stopped work and 344 (12.3%) changed jobs because of IA symptoms. There was a high burden of absenteeism (30%) and presenteeism (40%). Compared with managerial or professional workers, the burden of work disability was greater amongst those in routine (manual) occupations. During follow-up, 9.4% of WPAI completers had stopped work and 14.6% had changed roles. Work dropout occurred almost entirely amongst people doing routine jobs. CONCLUSION: IA associates with work disability within 12 months of diagnosis. It is easier to retain work in certain employment sectors. Participation in routine jobs is more affected, which may widen health inequalities.

Online Patient-Reported Outcome Measure Engagement Is Dependent on Demographics and Locality: Findings From an Observational Cohort.

OBJECTIVE: Online patient-reported outcome measures (PROMs) enable remote collection of perceptions of health status, function, and well-being. We aimed to explore patterns of PROM completion in patients with early inflammatory arthritis (EIA) recruited to the National Early Inflammatory Arthritis Audit (NEIAA). METHODS: NEIAA is an observational cohort study design; we included adults from this cohort with a new diagnosis of EIA from May 2018 to March 2020. The primary outcome was PROM completion at baseline, 3 months, and 12 months. Mixed effects logistic regression and spatial regression models were used to identify associations between demographics (age, gender, ethnicity, deprivation, smoking, and comorbidity), clinical commissioning groups, and PROM completion. RESULTS: Eleven thousand nine hundred eighty-six patients with EIA were included, of whom 5331 (44.5%) completed at least 1 PROM. Patients from ethnic minority backgrounds were less likely to return a PROM (adjusted odds ratio [aOR] 0.57, 95% CI 0.48-0.66). Greater deprivation (aOR 0.73, 95% CI 0.64-0.83), male gender (aOR 0.86, 95% CI 0.78-0.94), higher comorbidity burden (aOR 0.95, 95% CI 0.91-0.99), and current smoker status (aOR 0.73, 95% CI 0.64-0.82) also reduced odds of PROM completion. Spatial analysis identified 2 regions with high (North of England) and low (Southeast of England) PROM completion. CONCLUSION: We define key patient characteristics (including ethnicity) that influence PROM engagement using a national clinical audit. We observed an association between locality and PROM completion, with varying response rates across regions of England. Completion rates could benefit from targeted education for these groups.

Nonadherence to systemic immune-modifying therapy in people with psoriasis during the COVID-19 pandemic: findings from a global cross-sectional survey.

BACKGROUND: Nonadherence to immune-modifying therapy is a complex behaviour which, before the COVID-19 pandemic, was shown to be associated with mental health disorders in people with immune-mediated diseases. The COVID-19 pandemic has led to a rise in the global prevalence of anxiety and depression, and limited data exist on the association between mental health and nonadherence to immune-modifying therapy during the pandemic. OBJECTIVES: To assess the extent of and reasons underlying nonadherence to systemic immune-modifying therapy during the COVID-19 pandemic in individuals with psoriasis, and the association between mental health and nonadherence. METHODS: Online self-report surveys (PsoProtectMe), including validated screens for anxiety and depression, were completed globally during the first year of the pandemic. We assessed the association between anxiety or depression and nonadherence to systemic immune-modifying therapy using binomial logistic regression, adjusting for potential cofounders (age, sex, ethnicity, comorbidity) and country of residence. RESULTS: Of 3980 participants from 77 countries, 1611 (40.5%) were prescribed a systemic immune-modifying therapy. Of these, 408 (25.3%) reported nonadherence during the pandemic, most commonly due to concerns about their immunity. In the unadjusted model, a positive anxiety screen was associated with nonadherence to systemic immune-modifying therapy [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.07-1.76]. Specifically, anxiety was associated with nonadherence to targeted therapy (OR 1.41, 95% CI 1.01-1.96) but not standard systemic therapy (OR 1.16, 95% CI 0.81-1.67). In the adjusted model, although the directions of the effects remained, anxiety was not significantly associated with nonadherence to overall systemic (OR 1.20, 95% CI 0.92-1.56) or targeted (OR 1.33, 95% CI 0.94-1.89) immune-modifying therapy. A positive depression screen was not strongly associated with nonadherence to systemic immune-modifying therapy in the unadjusted (OR 1.22, 95% CI 0.94-1.57) or adjusted models (OR 1.14, 95% CI 0.87-1.49). CONCLUSIONS: These data indicate substantial nonadherence to immune-modifying therapy in people with psoriasis during the pandemic, with attenuation of the association with mental health after adjusting for confounders. Future research in larger populations should further explore pandemic-specific drivers of treatment nonadherence. Clear communication of the reassuring findings from population-based research regarding immune-modifying therapy-associated adverse COVID-19 risks to people with psoriasis is essential, to optimize adherence and disease outcomes.

Gout incidence and management during the COVID-19 pandemic in England, UK: a nationwide observational study using OpenSAFELY.

BACKGROUND: Gout is the most prevalent inflammatory arthritis, yet one of the worst managed. Our objective was to assess how the COVID-19 pandemic impacted incidence and quality of care for people with gout in England, UK. METHODS: With the approval of National Health Service England, we did a population-level cohort study using primary care and hospital electronic health record data for 17·9 million adults registered with general practices using TPP health record software, via the OpenSAFELY platform. The study period was from March 1, 2015, to Feb 28, 2023. Individuals aged 18-110 years were defined as having incident gout if they were assigned index diagnostic codes for gout, were registered with TPP practices in England for at least 12 months before diagnosis, did not receive prescriptions for urate-lowering therapy more than 30 days before diagnosis, and had not been admitted to hospital or attended an emergency department for gout flares more than 30 days before diagnosis. Outcomes assessed were incidence and prevalence of people with recorded gout diagnoses, incidence of gout hospitalisations, initiation of urate-lowering therapy, and attainment of serum urate targets (≤360 µmol/L). FINDINGS: From a reference population of 17 865 145 adults, 246 695 individuals were diagnosed with incident gout. The mean age of individuals with incident gout was 61·3 years (SD 16·2). 66 265 (26·9%) of 246 695 individuals were female, 180 430 (73·1%) were male, and 189 035 (90·9%) of 208 050 individuals with available ethnicity data were White. Incident gout diagnoses decreased by 30·9% in the year beginning March, 2020, compared with the preceding year (1·23 diagnoses vs 1·78 diagnoses per 1000 adults). Gout prevalence was 3·07% in 2015-16, and 3·21% in 2022-23. Gout hospitalisations decreased by 30·1% in the year commencing March, 2020, compared with the preceding year (9·6 admissions vs 13·7 admissions per 100 000 adults). Of 228 095 people with incident gout and available follow-up, 66 560 (29·2%) were prescribed urate-lowering therapy within 6 months. Of 65 305 individuals who initiated urate-lowering therapy with available follow-up, 16 790 (25·7%) attained a serum urate concentration of 360 µmol/L or less within 6 months of urate-lowering therapy initiation. In interrupted time-series analyses, urate-lowering therapy prescribing improved modestly during the pandemic, compared with pre-pandemic, whereas urate target attainment was similar. INTERPRETATION: Using gout as an exemplar disease, we showed the complexity of how health care was impacted during the COVID-19 pandemic. We observed a reduction in gout diagnoses but no effect on treatment metrics. We showed how country-wide, routinely collected data can be used to map disease epidemiology and monitor care quality. FUNDING: None.

Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.

Background: The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods: In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD. Findings: Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Interpretation: Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection. Funding: None.

Infection profile of immune-modulatory drugs used in autoimmune diseases: analysis of summary of product characteristic data.

OBJECTIVE: Serious infection remains a concern when prescribing immune-modulatory drugs for immune-mediated inflammatory diseases. The 'summary of product characteristics' (SmPCs) provide information on adverse events for example, infections, from clinical trials and postmarketing pharmacovigilance.This review aimed to compare infection frequency, site and type across immune-modulatory drugs, reported in SmPCs. METHODS: The Electronic Medicines Compendium was searched for commonly prescribed immune-modulatory drugs used for: rheumatoid arthritis, spondyloarthritis, connective tissue disease, autoimmune vasculitis, autoinflammatory syndromes, inflammatory bowel disease, psoriasis, multiple sclerosis and/or other rarer conditions.Information was extracted on infection frequency, site and organisms. Frequency was recorded as per the SmPCs: very common (≥1/10); common (≥1/100 to<1/10); uncommon (≥1/1,000 to<1/100); rare (≥1/10,000 to<1/1,000); very rare (<1/10 000). RESULTS: 39 drugs were included, across 20 indications: 9 conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), 6 targeted synthetic DMARDs, 24 biologic (b)DMARDs.Twelve infection sites were recorded. Minimal/no site information was available for most csDMARDs, certolizumab pegol and rituximab. Upper respiratory tract was the most common site, especially with bDMARDs. Lower respiratory, ear/nose/throat and urinary tract infections were moderately common, with clustering within drug groups.Data for 27 pathogens were recorded, majority viruses, with herpes simplex and zoster and influenza most frequent. Variable/absent reporting was noted for opportunistic and certain high-prevalence infections for example, Epstein-Barr. CONCLUSION: Our findings show differences between drugs and can aid treatment decisions alongside real-world safety data. However, data are likely skewed by trial selection criteria and varying number of trials per drug and highlight the need for robust postmarketing pharmacovigilance.

Risk of severe COVID-19 outcomes associated with immune-mediated inflammatory diseases and immune-modifying therapies: a nationwide cohort study in the OpenSAFELY platform.

Background: The risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases and on immune-modifying drugs might not be fully mediated by comorbidities and might vary by factors such as ethnicity. We aimed to assess the risk of severe COVID-19 in adults with immune-mediated inflammatory diseases and in those on immune-modifying therapies. Methods: We did a cohort study, using OpenSAFELY (an analytics platform for electronic health records) and TPP (a software provider for general practitioners), analysing routinely collected primary care data linked to hospital admission, death, and previously unavailable hospital prescription data. We included people aged 18 years or older on March 1, 2020, who were registered with TPP practices with at least 12 months of primary care records before March, 2020. We used Cox regression (adjusting for confounders and mediators) to estimate hazard ratios (HRs) comparing the risk of COVID-19-related death, critical care admission or death, and hospital admission (from March 1 to Sept 30, 2020) in people with immune-mediated inflammatory diseases compared with the general population, and in people with immune-mediated inflammatory diseases on targeted immune-modifying drugs (eg, biologics) compared with those on standard systemic treatment (eg, methotrexate). Findings: We identified 17 672 065 adults; 1 163 438 adults (640 164 [55·0%] women and 523 274 [45·0%] men, and 827 457 [71·1%] of White ethnicity) had immune-mediated inflammatory diseases, and 16 508 627 people (8 215 020 [49·8%] women and 8 293 607 [50·2%] men, and 10 614 096 [64·3%] of White ethnicity) were included as the general population. Of 1 163 438 adults with immune-mediated inflammatory diseases, 19 119 (1·6%) received targeted immune-modifying therapy and 181 694 (15·6%) received standard systemic therapy. Compared with the general population, adults with immune-mediated inflammatory diseases had an increased risk of COVID-19-related death after adjusting for confounders (age, sex, deprivation, and smoking status; HR 1·23, 95% CI 1·20-1·27) and further adjusting for mediators (body-mass index [BMI], cardiovascular disease, diabetes, and current glucocorticoid use; 1·15, 1·11-1·18). Adults with immune-mediated inflammatory diseases also had an increased risk of COVID-19-related critical care admission or death (confounder-adjusted HR 1·24, 95% CI 1·21-1·28; mediator-adjusted 1·16, 1·12-1·19) and hospital admission (confounder-adjusted 1·32, 1·29-1·35; mediator-adjusted 1·20, 1·17-1·23). In post-hoc analyses, the risk of severe COVID-19 outcomes in people with immune-mediated inflammatory diseases was higher in non-White ethnic groups than in White ethnic groups (as it was in the general population). We saw no evidence of increased COVID-19-related death in adults on targeted, compared with those on standard systemic, therapy after adjusting for confounders (age, sex, deprivation, BMI, immune-mediated inflammatory diseases [bowel, joint, and skin], cardiovascular disease, cancer [excluding non-melanoma skin cancer], stroke, and diabetes (HR 1·03, 95% CI 0·80-1·33), and after additionally adjusting for current glucocorticoid use (1·01, 0·78-1·30). There was no evidence of increased COVID-19-related death in adults prescribed tumour necrosis factor inhibitors, interleukin (IL)-12/IL­23 inhibitors, IL-17 inhibitors, IL-6 inhibitors, or Janus kinase inhibitors compared with those on standard systemic therapy. Rituximab was associated with increased COVID-19-related death (HR 1·68, 95% CI 1·11-2·56), with some attenuation after excluding people with haematological malignancies or organ transplants (1·54, 0·95-2·49). Interpretation: COVID-19 deaths and hospital admissions were higher in people with immune-mediated inflammatory diseases. We saw no increased risk of adverse COVID-19 outcomes in those on most targeted immune-modifying drugs for immune-mediated inflammatory diseases compared with those on standard systemic therapy. Funding: UK Medical Research Council, NIHR Biomedical Research Centre at King's College London and Guy's and St Thomas' NHS Foundation Trust, and Wellcome Trust.

Hospitalizations for Acute Gout: Process Mapping the Inpatient Journey and Identifying Predictors of Admission.

OBJECTIVE: To identify predictors of admission following emergency department (ED) attendances for gout flares and to describe barriers to optimal inpatient gout care. METHODS: ED attendances and hospital admissions with primary diagnoses of gout were analyzed at 2 UK-based hospitals between January 1, 2017, and December 31, 2020. Demographic and clinical predictors of ED disposition (admission or discharge) and reattendance for gout flares were identified using logistic regression and survival models, respectively. Case note reviews (n = 59), stakeholder meetings, and process mapping were performed to capture detailed information on gout management and to identify strategies to optimize care. RESULTS: Of 1220 emergency attendances for gout flares, 23.5% required hospitalization (median length of stay: 3.6 days). Recurrent attendances for flares occurred in 10.4% of patients during the study period. In multivariate logistic regression models, significant predictors of admission from ED were older age, overnight ED arrival time, higher serum urate (SU), higher C-reactive protein, and higher total white cell count at presentation. Detailed case note reviews showed that only 22.6% of patients with preexisting gout were receiving urate-lowering therapy (ULT) at presentation. Initial diagnostic uncertainty was common, yet rheumatology input and synovial aspirates were rarely obtained. By 6 months postdischarge, 43.6% were receiving ULT; however, few patients had treat-to-target dose optimization, and only 9.1% achieved SU levels ≤ 360 µmol/L. CONCLUSION: We identified multiple predictors of hospitalization for acute gout. Treat-to-target optimization of ULT following hospitalization remains inadequate and must be improved if admissions are to be prevented.