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.

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 COVID-19 hospitalisation and mortality amongst 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-May 2021. Outcomes of interest were hospitalisation 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 hospitalisations and 47 deaths due to COVID-19: incidence rates per 100 person-years of 0.93 (95% CI 0.79-1.10) for hospitalisation 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 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, corticosteroids associated with COVID-19 death (HR 2.29; 95% CI 1.02-5.13), and sulfasalazine monotherapy associated with COVID-19 admission (HR 1.92; 95% CI 1.04-3.56). In adjusted models, associations for corticosteroids and sulfasalazine 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.

IL-6 inhibition in the treatment of COVID-19: A meta-analysis and meta-regression.

OBJECTIVES: Multiple RCTs of interleukin-6 (IL-6) inhibitors in COVID-19 have been published, with conflicting conclusions. We performed a meta-analysis to assess the impact of IL-6 inhibition on mortality from COVID-19, utilising meta-regression to explore differences in study results. METHODS: Systematic database searches were performed to identify RCTs comparing IL-6 inhibitors (tocilizumab and sarilumab) to placebo or standard of care in adults with COVID-19. Meta-analysis was used to estimate the relative risk of mortality at 28 days between arms, expressed as a risk ratio. Within-study mortality rates were compared, and meta-regression was used to investigate treatment effect modification. RESULTS: Data from nine RCTs were included. The combined mortality rate across studies was 19% (95% CI: 18, 20%), ranging from 2% to 31%. The overall risk ratio for 28-day mortality was 0.90 (95% CI: 0.81, 0.99), in favour of benefit for IL-6 inhibition over placebo or standard of care, with low treatment effect heterogeneity: I2 0% (95% CI: 0, 53%). Meta-regression showed no evidence of treatment effect modification by patient characteristics. Trial-specific mortality rates were explained by known patient-level predictors of COVID-19 outcome (male sex, CRP, hypertension), and country-level COVID-19 incidence. CONCLUSIONS: IL-6 inhibition is associated with clinically meaningful improvements in outcomes for patients admitted with COVID-19. Long-term benefits of IL-6 inhibition, its effectiveness across healthcare systems, and implications for differing standards of care are currently unknown.

A clinical risk score to identify patients with COVID-19 at high risk of critical care admission or death: An observational cohort study.

BACKGROUND: The COVID-19 pandemic continues to escalate. There is urgent need to stratify patients. Understanding risk of deterioration will assist in admission and discharge decisions, and help selection for clinical studies to indicate where risk of therapy-related complications is justified. METHODS: An observational cohort of patients acutely admitted to two London hospitals with COVID-19 and positive SARS-CoV-2 swab results was assessed. Demographic details, clinical data, comorbidities, blood parameters and chest radiograph severity scores were collected from electronic health records. Endpoints assessed were critical care admission and death. A risk score was developed to predict outcomes. FINDINGS: Analyses included 1,157 patients. Older age, male sex, comorbidities, respiratory rate, oxygenation, radiographic severity, higher neutrophils, higher CRP and lower albumin at presentation predicted critical care admission and mortality. Non-white ethnicity predicted critical care admission but not death. Social deprivation was not predictive of outcome. A risk score was developed incorporating twelve characteristics: age>40, male, non-white ethnicity, oxygen saturations<93%, radiological severity score>3, neutrophil count>8.0 x109/L, CRP>40 mg/L, albumin<34 g/L, creatinine>100 µmol/L, diabetes mellitus, hypertension and chronic lung disease. Risk scores of 4 or higher corresponded to a 28-day cumulative incidence of critical care admission or death of 40.7% (95% CI: 37.1 to 44.4), versus 12.4% (95% CI: 8.2 to 16.7) for scores less than 4. INTERPRETATION: Our study identified predictors of critical care admission and death in people admitted to hospital with COVID-19. These predictors were incorporated into a risk score that will inform clinical care and stratify patients for clinical trials.