Incidence and Management of Inflammatory Arthritis in England before and during the Covid- 19 Pandemic: A Population-Level Cohort Study Using Opensafely

Background/Aims The impact of the pandemic on the incidence and management of inflammatory arthritis (IA) is not understood. Routinely-captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how IA 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 IA in England, and replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods With the approval of NHS England, we used primary care and hospital data for 17 million adults registered with general practices using TPP health record software, to explore the following outcomes between 1 April 2019 and 31 March 2022: 1) incidence of IA diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) recorded in primary care;2) time to first rheumatology assessment;3) time to first prescription of a conventional synthetic DMARD (csDMARD) in primary care, and choice of first csDMARD. Results From 17,683,500 adults (representing 40% of the English population), there were 31,280 incident IA diagnoses recorded between April 2019 and March 2022. New IA diagnoses decreased by 39.7% in the early months of the pandemic. Overall, a 20.3% decrease in IA diagnoses was seen in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). Further decreases coincided with rising COVID-19 numbers, before returning to pre-pandemic levels by the end of the study period. No rebound increase in IA incidence was observed as of April 2022. The median time from referral to first rheumatology assessment was shorter during the pandemic (18 days;IQR 8-35 days) than before (21 days;9-41 days). The proportion of patients prescribed csDMARDs in primary care was comparable to before the pandemic;however, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Conclusion IA diagnoses decreased markedly during the early phase of the pandemic;however, the impact on rheumatology assessment times and DMARD prescribing was less marked than might have been anticipated. This study demonstrates the feasibility of using routinelycaptured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection.

COVID-19 ADMISSIONS AND MORTALITY IN PATIENTS WITH EARLY INFLAMMATORY ARTHRITIS: RESULTS FROM A NATIONAL COHORT

Background/Aims Patients with inflammatory arthritis were identified as a potentially vulnerable group during the COVID-19 pandemic, with recommendations from the UK government to shield. We set out to describe the risks of COVID-19 according to initial treatment strategy amongst patients recruited to the National Early Inflammatory Arthritis Audit (NEIAA). Methods NEIAA is an observational cohort design. It includes adults in England with a new diagnosis of inflammatory arthritis between May 2018 and March 2021. The outcomes of interest were death due to COVID-19 (COVID-19 stated on a death certificate) and hospitalisation due to COVID-19 (primary admission reason or nosocomial acquisition), identified using NHS Digital linkage. Cox proportional hazards models were used to calculate hazard ratios, with adjustment for patient factors (age, gender, smoking status, comorbidity) and disease factors (seropositivity, disease severity (DAS28), patient-reported disability (HAQ) and functional impact (MSK-HQ)) recorded at baseline. Individuals were considered at risk from February 2020 or date of diagnosis (whichever was later) and censored at a COVID-19 event, May 2021 or death (whichever was sooner). Results 14,127 patients were included. Mean age was 57 (+/-16);62% were female. Smoking status: 19% current;29% ex-smokers. Comorbidities: 19% hypertension;9% diabetes;and 9% lung disease. Overall, 20% had two or more comorbidities. Rheumatoid Factor or CCP antibodies were positive in 56%. At presentation, mean scores were 4.6 (+/-1.5) for DAS28, 1.1 (+/-0.7) for HAQ and 25 (+/-11) for MSK-HQ. Initial DMARD therapy was known for 13,682/14,127 patients;methotrexate was most common (54%), then hydroxychloroquine (23%) and sulfasalazine (11%). There were 143 COVID-19 hospital admissions and 47 deaths, corresponding to incidence rates per 100 person-years for hospitalisation: 0.94 (95% CI: 0.79-1.10) and death: 0.31 (95% CI: 0.23-0.41). Increasing age, male gender, diabetes, hypertension, lung disease and smoking status all predicted COVID-19 events. Higher baseline DAS28 predicted COVID-19 admission (HR 1.24 (95% CI: 1.10-1.39)) and mortality (HR 1.33 (95% CI: 1.09-1.63)). Higher HAQ predicted both COVID-19 admission and death. Seropositivity was not a significant predictor of any COVID- 19 event, nor was MSK-HQ. Unadjusted, corticosteroids associated with COVID-19 death (HR 2.29 (95% CI: 1.02-5.13)), and sulfasalazine monotherapy associated with COVID-19 admission (HR 1.93 (95% CI: 1.04-3.56)). In adjusted models, associations for corticosteroids and sulfasalazine were no longer significant. Only age, smoking status, and comorbidities independently predicted COVID-19 events. Conclusion The burden of COVID-19 amongst early arthritis patients was substantial during the pandemic. Patient characteristics and rheumatoid disease severity at diagnosis appear to be the more important predictors of COVID-19 events than initial treatment strategy. An important limitation is that we have not looked at treatment changes over time, and must acknowledge that many patients, especially those recruited in 2019, may have changed therapy prior to the pandemic.

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.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.