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.

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.

JAK inhibitors and the risk of malignancy: a meta-analysis across disease indications.

OBJECTIVES: To estimate the association of Janus kinase inhibitors (JAKi) with the incidence of malignancy, compared with placebo, tumour necrosis factor (TNF)-α inhibitors (TNFi) and methotrexate. METHODS: Systematic searches of databases were performed, to December 2022, to identify phase II/III/IV randomised clinical trials (RCTs) and long-term extension (LTE) studies of JAKi (tofacitinib, baricitinib, upadacitinib, filgotinib, peficitinib) compared with placebo, TNFi or methotrexate, in adults with rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, inflammatory bowel disease or atopic dermatitis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy between JAKi and comparators. Bias was assessed using the Cochrane Risk of Bias-2 tool. RESULTS: In 62 eligible RCTs and 16 LTE studies, there were 82 366 person-years of exposure to JAKi, 2924 to placebo, 7909 to TNFi and 1074 to methotrexate. The overall malignancy incidence rate was 1.15 per 100 person-years in RCTs, and 1.26 per 100 person-years across combined RCT and LTE data. In network meta-analyses, the incidence of all malignancies including non-melanomatous skin cancers (NMSCs) was not significantly different between JAKi and placebo (IRR 0.71; 95% CI 0.44 to 1.15) or between JAKi and methotrexate (IRR 0.77; 95% CI 0.35 to 1.68). Compared with TNFi, however, JAKi were associated with an increased incidence of malignancy (IRR 1.50; 95% CI 1.16 to 1.94). Findings were consistent when analysing NMSC only and when analysing combined RCT/LTE data. CONCLUSIONS: JAKi were associated with a higher incidence of malignancy compared with TNFi but not placebo or methotrexate. Cancers were rare events in all comparisons. PROSPERO REGISTRATION NUMBER: CRD42022362630.

The Clinical Impact of Electronic Patient-Reported Outcome Measures in the Remote Monitoring of Inflammatory Arthritis: A Systematic Review and Meta-analysis.

OBJECTIVE: The inflammatory arthritides (IAs) make up a significant proportion of conditions followed up in rheumatology clinics. These patients require regular monitoring, but this is increasingly difficult with rising patient numbers and demand on clinics. Our objective is to evaluate the clinical impact of electronic patient-reported outcome measures (ePROMs) as a digital remote-monitoring intervention on disease activity, treatment decisions, and health care resource use in patients with IA. METHODS: Five databases (MEDLINE, Embase, PubMed, Cochrane Library, and Web of Science) were searched, with randomized controlled trials and (nonrandomized) controlled clinical trials included, and meta-analysis and forest plots conducted for each outcome. Risk of bias was assessed using the Risk of Bias-2 tool and Risk of Bias in Nonrandomized Studies of Interventions. RESULTS: Eight studies were included with a total of 4,473 patients, with seven studies assessing patients with rheumatoid arthritis. Compared with control, the disease activity in the ePROM group was lower (standardized mean difference [SMD] -0.15; 95% confidence interval [CI] -0.27 to -0.03) and rates of remission/low disease activity were higher (odds ratio1.65; 95% CI 1.02-2.68), but five of eight studies provided additional combined interventions (e.g., disease education). Fewer face to face visits were needed in the remote ePROM group (SMD -0.93; 95% CI -2.14-0.28). CONCLUSION: Most studies were at high risk of bias with significant heterogeneity in design, but our results suggest there is an advantage in using ePROM monitoring in patients with IAs, with the potential for reduction in health care resource use without detrimental impact in disease outcomes.

COVID-19 admissions and mortality in patients with early inflammatory arthritis: results from a UK national cohort.

OBJECTIVE: To describe the risks and predictors of coronavirus disease 2019 (COVID-19) hospitalization and mortality among patients with early inflammatory arthritis (EIA), recruited to the National Early Inflammatory Arthritis Audit (NEIAA). METHODS: NEIAA is an observational cohort. We included adults with EIA from Feb 2020 to May 2021. Outcomes of interest were hospitalization and death due to COVID-19, using NHS Digital linkage. Cox proportional hazards were used to calculate hazard ratios for outcomes according to initial treatment strategy, with adjustment for confounders. RESULTS: From 14 127 patients with EIA, there were 143 hospitalizations and 47 deaths due to COVID-19, with incidence rates per 100 person-years of 0.93 (95% CI 0.79, 1.10) for hospitalization and 0.30 (95% CI 0.23, 0.40) for death. Increasing age, male gender, comorbidities and ex-smoking were associated with increased risk of worse COVID-19 outcomes. Higher baseline DAS28 was not associated with COVID-19 admissions [confounder adjusted hazard ratio (aHR) 1.10; 95% CI 0.97, 1.24] or mortality (aHR 1.11; 95% CI 0.90, 1.37). Seropositivity was not associated with either outcome. Higher symptom burden on patient-reported measures predicted worse COVID-19 outcomes. In unadjusted models, CS associated with COVID-19 death (HR 2.29; 95% CI 1.02, 5.13), and SSZ monotherapy associated with COVID-19 admission (HR 1.92; 95% CI 1.04, 3.56). In adjusted models, associations for CS and SSZ were not statistically significant. CONCLUSION: Patient characteristics have stronger associations with COVID-19 than the initial treatment strategy in patients with EIA. An important limitation is that we have not looked at treatment changes over time.

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.

Changing trends in ethnicity and academic performance: observational cohort data from a UK medical school.

OBJECTIVE: Quantify differential attainment by ethnicity in undergraduate medical assessments and evaluate whether institutional efforts to reduce the attainment gap have had impact. DESIGN: Observational cohort study. SETTING: A single UK MBBS medical programme. PARTICIPANTS: Pseudonymised data of adults aged ≥18 years enrolled in one of the UK MBBS medical programmes between 2012 and 2018. Ethnicity was self-declared during enrolment as White, Asian, Black, mixed and other. MAIN OUTCOME MEASURE: Module mark (distinction, merit, pass, fail) graded according to a variety of assessments, including single best answer examinations, objective structured clinical examinations and coursework submissions. All modular assessments are graded as a percentage. Logistic regression models were used to calculate relative risk ratio to study the association between ethnicity and attainment gap over a calendar and scholastic year. Models were adjusted for age, gender, social deprivation and scholastic year of study. RESULTS: 3714 student records were included. In the sample, 2134 students (57%) were non-white. The proportion of non-white students increased from 2007 (49%) to 2018 (70%). Mean age was 18 (IQR 18-21) and 56.6% were females. Higher proportion of non-white students 218 (24.8%) were from more deprived backgrounds versus white 76 (14.8%). Compared with non-white, there were no significant differences in the proportion of students failing assessments. However, white students were more likely to achieve merit (relative risk ratio 1.29 (95% CI 1.08 to 1.45)) or distinction (1.69 (95% CI 1.37 to 2.08)). Differences in attainment gap have remained unchanged over time, and for black students, attainment gap grew between their first and final year of study. CONCLUSION: A similar proportion (97%) of non-white and white students had a passing score, but attainment gap for higher grades persists over years despite widespread efforts in medical schools to diminish the attainment gap linked to ethnicity. Our findings are from a single institution, thus affecting generalisability.

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.

Worse outcomes linked to ethnicity for early inflammatory arthritis in England and Wales: a national cohort study.

OBJECTIVE: To assess variability in care quality and treatment outcomes across ethnicities in early inflammatory arthritis (EIA). METHODS: We conducted an observational cohort study in England and Wales from May 2018 to March 2020, including patients with a suspected/confirmed EIA diagnosis. Care quality was assessed against six metrics defined by national guidelines. Clinical outcomes were measured using DAS28. Outcomes between ethnic groups ('White', 'Black', 'Asian', 'Mixed', 'Other') were compared, and adjusted for confounders. RESULTS: A total of 35 807 eligible patients were analysed. Of those, 30 643 (85.6%) were White and 5164 (14.6%) were from ethnic minorities: 1035 (2.8%) Black; 2617 (7.3%) Asian; 238 (0.6%) Mixed; 1274 (3.5%) Other. In total, 12 955 patients had confirmed EIA, of whom 11 315 were White and 1640 were from ethnic minorities: 314 (2.4%) Black; 927 (7.1%) Asian; 70 (0.5%) Mixed; 329 (2.5%) Other. A total of 14 803 patients were assessed by rheumatology within three weeks, and 5642 started treatment within six weeks of referral. There were no significant differences by ethnicity. Ethnic minority patients had lower odds of disease remission at three months [adjusted odds ratio 0.79 (95% CI: 0.65, 0.96)] relative to White patients. Ethnic minorities were significantly less likely to receive initial treatment withMTX[0.68 (0.52, 0.90)] or with glucocorticoids [0.63 (0.49, 0.80)]. CONCLUSION: We demonstrate that some ethnic minorities are less likely to achieve disease remission in three months following EIA diagnosis. This is not explained by delays in referral or time to treatment. Our data highlight the need for investigation into the possible drivers of these inequitable outcomes and reappraisal of EIA management pathways.

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.

Skeletal muscles and Covid-19: a systematic review of rhabdomyolysis and myositis in SARS-CoV-2 infection.

OBJECTIVES: Myalgia is a widely publicised feature of Covid-19, but severe muscle injury can occur. This systematic review summarises relevant evidence for skeletal muscle involvement in Covid-19. METHODS: A systematic search of OVID and Medline databases was conducted on 16/3/2021 and updated on 28/10/2021 to identify case reports or observational studies relating to skeletal muscle manifestations of Covid-19 (PROSPERO: CRD42020198637). Data from rhabdomyolysis case reports were combined and summary descriptive statistics calculated. Data relating to other manifestations were analysed for narrative review. RESULTS: 1920 articles were identified. From these, 61 case reports/series met inclusion criteria, covering 86 rhabdomyolysis cases. Median age of rhabdomyolysis patients was 50 years, (range 6-89). 49% had either hypertension, diabetes mellitus or obesity. 77% were male. Symptoms included myalgia (74%), fever (69%), cough (59%), dyspnoea (68%). Median peak CK was 15,783U/L. 28% required intravenous haemofiltration and 36% underwent mechanical ventilation. 62% recovered to discharge and 30% died. Dyspnoea, elevated CRP and need for intravenous haemofiltration increased risk of fatal outcome. Additional articles relating to skeletal muscular pathologies include 6 possible concomitant diagnoses or relapses of idiopathic inflammatory myopathies and 10 reports of viral-induced muscle injuries without rhabdomyolysis. Localised myositis and rhabdomyolysis with SARS-CoV-2 vaccination have been reported. CONCLUSIONS: Rhabdomyolysis is an infrequent but important complication of Covid-19. Increased mortality was associated with a high CRP, renal replacement therapy and dyspnoea. The idiopathic inflammatory myopathies (IIM) may have viral environmental triggers. However, to date the limited number of case reports do not confirm an association with Covid-19.

The infection risks of JAK inhibition.

INTRODUCTION: Janus Kinase inhibitors (JAKi) have shown to be highly effective in the treatment of immune-mediated inflammatory diseases. As with all immunomodulatory therapies, careful assessment of any treatment-associated infection risk is essential to inform clinical decision-making. AREAS COVERED: We summarize current literature on infection rates among the licensed JAKi using published phase II/III trial results, post-licensing and registry data. EXPERT OPINION: licensed JAKi show increased risk of infection across the class compared to placebo, most commonly affecting respiratory and urinary tracts, nasopharynx and skin. This risk is dose-dependent. Risks are similar at licensed JAKi doses to that seen with biologic therapies. The risk is compounded by other risk factors for infection, such as age and steroid co-prescription. Herpes zoster reactivation is more common with JAKi compared to other targeted immune modulation, making screening for varicella exposure and vaccination in appropriate cohorts an advisable strategy. Crucially, these small risk increases must be balanced against the known harms (including infection) of uncontrolled autoimmune disease. JAKi are a safe and potentially transformative treatment when used for appropriately selected patients.

A systematic review and network meta-analysis of the safety of early interventional treatments in rheumatoid arthritis.

OBJECTIVES: To evaluate the safety of treatment strategies in patients with early RA. METHODS: Systematic searches of MEDLINE, EMBASE and PubMed were conducted up to September 2020. Double-blind randomized controlled trials (RCTs) of licensed treatments conducted on completely naïve or MTX-naïve RA patients were included. Long-term extension studies, post-hoc and pooled analyses and RCTs with no comparator arm were excluded. Serious adverse events, serious infections and non-serious adverse events were extracted from all RCTs, and event rates in intervention and comparator arms were compared using meta-analysis and network meta-analysis (NMA). RESULTS: From an initial search of 3423 studies, 20 were included, involving 9202 patients. From the meta-analysis, the pooled incidence rates per 1000 patient-years for serious adverse events were 69.8 (95% CI: 64.9, 74.8), serious infections 18.9 (95% CI: 16.2, 21.6) and non-serious adverse events 1048.2 (95% CI: 1027.5, 1068.9). NMA showed that serious adverse event rates were higher with biologic monotherapy than with MTX monotherapy, rate ratio 1.39 (95% CI: 1.12, 1.73). Biologic monotherapy rates were higher than those for MTX and steroid therapy, rate ratio 3.22 (95% CI: 1.47, 7.07). Biologic monotherapy had a higher adverse event rate than biologic combination therapy, rate ratio 1.26 (95% CI: 1.02, 1.54). NMA showed no significant difference between strategies with respect to serious infections and non-serious adverse events rates. CONCLUSION: The study revealed the different risk profiles for various early RA treatment strategies. Observed differences were overall small, and in contrast to the findings of established RA studies, steroid-based regimens did not emerge as more harmful.