Safety and Efficacy of NVX-CoV2373 Covid-19 Vaccine.

BACKGROUND: Early clinical data from studies of the NVX-CoV2373 vaccine (Novavax), a recombinant nanoparticle vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that contains the full-length spike glycoprotein of the prototype strain plus Matrix-M adjuvant, showed that the vaccine was safe and associated with a robust immune response in healthy adult participants. Additional data were needed regarding the efficacy, immunogenicity, and safety of this vaccine in a larger population. METHODS: In this phase 3, randomized, observer-blinded, placebo-controlled trial conducted at 33 sites in the United Kingdom, we assigned adults between the ages of 18 and 84 years in a 1:1 ratio to receive two intramuscular 5-µg doses of NVX-CoV2373 or placebo administered 21 days apart. The primary efficacy end point was virologically confirmed mild, moderate, or severe SARS-CoV-2 infection with an onset at least 7 days after the second injection in participants who were serologically negative at baseline. RESULTS: A total of 15,187 participants underwent randomization, and 14,039 were included in the per-protocol efficacy population. Of the participants, 27.9% were 65 years of age or older, and 44.6% had coexisting illnesses. Infections were reported in 10 participants in the vaccine group and in 96 in the placebo group, with a symptom onset of at least 7 days after the second injection, for a vaccine efficacy of 89.7% (95% confidence interval [CI], 80.2 to 94.6). No hospitalizations or deaths were reported among the 10 cases in the vaccine group. Five cases of severe infection were reported, all of which were in the placebo group. A post hoc analysis showed an efficacy of 86.3% (95% CI, 71.3 to 93.5) against the B.1.1.7 (or alpha) variant and 96.4% (95% CI, 73.8 to 99.5) against non-B.1.1.7 variants. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups. CONCLUSIONS: A two-dose regimen of the NVX-CoV2373 vaccine administered to adult participants conferred 89.7% protection against SARS-CoV-2 infection and showed high efficacy against the B.1.1.7 variant. (Funded by Novavax; EudraCT number, 2020-004123-16.).

Potential impact of European Medicines Agency measures to minimise risk of serious side effects on JAKi prescribing and utilisation in the UK.

OBJECTIVE: Janus kinase inhibitors (JAKi) or targeted synthetic (ts) disease-modifying antirheumatic drugs (DMARDs) effectively treat rheumatoid arthritis (RA). However, due to safety concerns, the European Medicines Agency (EMA) published risk minimisation measures limiting JAKi prescription to certain at-risk patients unless no suitable alternative is available. This analysis included patients who had started their first-ever JAKi before EMA measures were published in a large national cohort study to investigate the potential impact of these measures on JAKi prescribing and utilisation in UK. METHOD: RA patients starting first-ever JAK inhibitor therapy in BSRBR-RA between 13-February-2017 and 31-May-2022 were included. Percentages of patients meeting EMA risk criteria were presented. For at-risk patients, previous number of distinct biological (b) DMARD classes were described. RESULT: A total of 1341 patients were included, and 80% (N = 1075) met ≥1 EMA risk criterion. Of those who met ≥1 risk criterion, 529 patients (49%) had received JAKi as their first or second b/tsDMARD class, whereas 299 (28%) had received ≥3 prior bDMARD classes. CONCLUSION: Four-in-five RA patients commencing JAKi before the EMA advisory were considered 'at-risk' with prescribing only advised if there was no suitable alternative. Almost a third of those patients had already received ≥3 bDMARDs classes, and alternative therapies would be very limited for them; meanwhile, suitable alternatives might have existed for the remaining proportion, especially for those who received JAKi as their first or second b/tsDMARD, and re-evaluation of the suitability of their treatment may be needed.

Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort.

OBJECTIVES: People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during 12-months following IA diagnosis, mapping these against clinical outcomes to identify associations. METHODS: This is a prospective study of people recruited to NEIAA receiving an IA diagnosis and completing the baseline patient survey. Patient reported outcomes (PROs) at baseline, 3-months and 12-months were collected, including psychological distress (assessed using Patient Health Questionnaire Anxiety and Depression Screener (PHQ4ADS)). Mixed effects linear regression models estimated associations between predictor variables with psychological distress at baseline and over time. RESULTS: Of 6,873 eligible patients, 3,451 (50.2%) showed psychological distress at baseline. Of those completing follow-ups, 30.0% and 24.1% were distressed at 3-months and 12-months, respectively. Higher psychological distress at diagnosis was more commonly reported by younger, female, and non-white patients. Clinical factors, including higher counts of comorbidities, prior depression, and higher disease activity at diagnosis were associated with higher distress. Higher distress at baseline was associated with poorer outcomes over time in quality of life, disability, work performance, disease activity, as well as reduced likelihood of achieving good treatment response by EULAR criteria. CONCLUSION: Half of patients with IA show significant mental health comorbidity at presentation, which associated with worse disease outcomes and quality of life. Screening for anxiety and depression should be a universal standard, and access to effective mood therapies alongside arthritis treatments is essential. Strategies should be culturally valid and consider multi-morbidities.

Socioeconomic deprivation is associated with reduced response and lower treatment persistence with TNF inhibitors in rheumatoid arthritis.

OBJECTIVE: To investigate the association between socioeconomic deprivation and outcomes following TNF inhibitor (TNFi) treatment. METHODS: Individuals commencing their first TNFi in the British Society for Rheumatology Biologics Register for RA (BSRBR-RA) and Biologics in RA Genetics and Genomics Study Syndicate (BRAGGSS) cohort were included. Socioeconomic deprivation was proxied using the Index of Multiple Deprivation and categorized as 20% most deprived, middle 40% or 40% least deprived. DAS28-derived outcomes at 6 months (BSRBR-RA) and 3 months (BRAGGSS) were compared using regression models with the least deprived as referent. Risks of all-cause and cause-specific drug discontinuation were compared using Cox models in the BSRBR-RA. Additional analyses adjusted for lifestyle factors (e.g. smoking, BMI) as potential mediators. RESULTS: 16 085 individuals in the BSRBR-RA were included (mean age 56 years, 76% female), of whom 18%, 41% and 41% were in the most, middle and least deprived groups, respectively. Of 3459 included in BRAGGSS (mean age 57, 77% female), proportions were 22%, 36% and 41%, respectively. The most deprived group had 0.3-unit higher 6-month DAS28 (95% CI 0.22, 0.37) and were less likely to achieve low disease activity (odds ratio [OR] 0.76; 95% CI 0.68, 0.84) in unadjusted models. Results were similar for 3-month DAS28 (ß = 0.23; 95% CI 0.11, 0.36) and low disease activity (OR 0.77; 95% CI 0.63, 0.94). The most deprived were more likely to discontinue treatment (hazard ratio 1.18; 95% CI 1.12, 1.25), driven by ineffectiveness rather than adverse events. Adjusted estimates were generally attenuated. CONCLUSION: Socioeconomic deprivation is associated with reduced response to TNFi. Improvements in determinants of health other than lifestyle factors are needed to address socioeconomic inequities.

Pneumococcal vaccine uptake in patients with inflammatory arthritis: a single centre cohort study.

INTRODUCTION: Current guidelines recommend pneumococcal vaccination in individuals who are over the age of 65 or are immunosuppressed due to a disease or treatment. The objective of this study was to assess vaccine uptake rates in people with inflammatory arthritis for the pneumococcal, influenza and Covid-19 vaccines and factors determining uptake. METHODS: We conducted a retrospective single centre cohort study in the UK of individuals with rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis between October and December 2023. Data were collected for age, gender, co-morbidities, immunosuppressive therapies, and dates of vaccines. Logistic regression was used to evaluate predictors of vaccine uptake, with adjustments for demographic and clinical factors. RESULTS: 906 individuals were identified. 46% were receiving treatment with csDMARD, 26% on biologic monotherapy, and 23% were on both biologic and csDMARDs. 316 individuals (35%) received a pneumococcal vaccine, lower than uptake for influenza (63%) and Covid-19 (87%) vaccines. Predictors of pneumococcal vaccine uptake included age, with older patients more likely to be vaccinated (odds ratio [OR] for age ≥ 65 years: 1.67, 95% CI 1.21-2.29). Those on biological therapy demonstrated higher likelihood of vaccination (OR for biologic therapy: 1.81, 95% CI 1.33-2.47). Additional Joint committee for immunisation and vaccination (JCVI) Green Book indicators also positively influenced vaccine uptake (OR: 1.67, 95% CI 1.19-2.33). CONCLUSION: Pneumococcal vaccine uptake in inflammatory rheumatic diseases is low, especially in younger patients and those not on biological therapy. The study highlights the need for a focused approach, distinct from strategies for other vaccines, to address this public health challenge.

Enhancing current guidance for psoriatic arthritis and its comorbidities: recommendations from an expert consensus panel.

OBJECTIVES: Existing guidelines for psoriatic arthritis (PsA) cover many aspects of management. Some gaps remain relating to routine practice application. An expert group aimed to enhance current guidance and develop recommendations for clinical practice that are complementary to existing guidelines. METHODS: A steering committee comprising experienced, research-active clinicians in rheumatology, dermatology and primary care agreed on themes and relevant questions. A targeted literature review of PubMed and Embase following a PICO framework was conducted. At a second meeting, recommendations were drafted and subsequently an extended faculty comprising rheumatologists, dermatologists, primary care clinicians, specialist nurses, allied health professionals, non-clinical academic participants and members of the Brit-PACT patient group, was recruited. Consensus was achieved via an online voting platform when 75% of respondents agreed in the range of 7-9 on a 9-point scale. RESULTS: The guidance comprised 34 statements covering four PsA themes. Diagnosis focused on strategies to identify PsA early and refer appropriately, assessment of diagnostic indicators, use of screening tools and use of imaging. Disease assessment centred on holistic consideration of disease activity, physical functioning and impact from a patient perspective, and on how to implement shared decision-making. For comorbidities, recommendations included specific guidance for high-impact conditions such as depression and obesity. Management statements (which excluded extant guidance on pharmacological therapies) covered multidisciplinary team working, implementation of lifestyle modifications and treat-to-target strategies. Minimising corticosteroid use was recommended where feasible. CONCLUSION: The consensus group have made evidence-based best practice recommendations for the management of PsA to enhance the existing guidelines.

De-escalation of corticosteroids and clonal remission in UBA1 mutation-driven VEXAS syndrome with 5-azacytidine.

Not available.

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.

The predictive role of symptoms in COVID-19 diagnostic models: A longitudinal insight.

To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%-22.7%) in participants reporting loss of appetite and 31.9% (27.1%-36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms' dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.

Ongoing shielding behavior one year post COVID-19: results from a longitudinal study of patients with inflammatory arthritis.

Many patients with inflammatory arthritis (IA) were instructed to shield during the COVID-19 pandemic. Despite the ending of lockdowns and vaccination, large proportions of IA patients were continuing to shield when it is no longer needed. Given the detrimental effects of shielding on mental and physical health, understanding the rates and reasons for shielding is needed to help clinicians advise patients accordingly. This study was a 12-month prospective study following participants with IA during the COVID-19 pandemic. The proportions of IA patients shielding at each time point were calculated. Additionally, regressions and odds ratios for shielding were determined to assess medication type, mental health, and risk perception. While the extent of shielding fluctuated over the year of lockdowns, nearly all IA patients (93.5%) were still engaging in some shielding in 2021, with nearly half (43%) still shielding most or all of the time. Medications that were previously considered higher risk were not significantly associated with higher rates of shielding (OR = 1.60, p = 0.29), but greater symptoms of depression in June 2020 (OR = 1.07, p = 0.03) was both associated with increased the odds of shielding in June 2021. The high rates of IA patients continuing to shield in 2021 put more strain on patients and professionals as social isolation is linked with worsening mental and physical health, as well as greater difficulty with self-management. It is important for clinicians to be aware of this trend to ease the stress on patients.

Real-world environmental enrichment rehabilitation paradigm in people with severe traumatic brain injury: a pilot feasibility study.

BACKGROUND: The use of Environmental Enrichment (EE) has been widely studied in animal models. However, the application of the same in humans is limited to rehabilitation settings. OBJECTIVE: To investigate the feasibility of a community-based EE paradigm in adults with brain injury. METHODS: Six individuals diagnosed with traumatic brain injury enrolled in the study. The Go Baby Go Café instrumented with a body weight harness system, provided physical and social enrichment as participants performed functional tasks for 2 hours, three times a week, for 2 months. Feasibility and safety outcomes were recorded throughout sessions. Clinical measures including 10-meter walk, timed up and go, jebsen hand function, 6-minute walk, and trail making tests were obtained pre and post intervention. RESULTS: All participants completed the study. The attendance was 100% and adherence was 87%. Positive changes in clinical measures were statistically significant for the timed up and go (p = 0.0175), TUG-cognitive (p = 0.0064), 10-meter walk (p = 0.0428), six-minute walk (p = 0.0196), TMT-A (p = 0.034). Changes in JHFT were not significant (p = 0.0506), with one subject recording values counter to the trend. CONCLUSION: The Café was a comprehensive EE-based intervention that was feasible, safe, and has the potential to enhance motor and cognitive function in individuals with brain injury.

Safety and Efficacy of the NVX-CoV2373 Coronavirus Disease 2019 Vaccine at Completion of the Placebo-Controlled Phase of a Randomized Controlled Trial.

BACKGROUND: The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. METHODS: Adults aged 18-84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. RESULTS: Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%-88.8%). Vaccine efficacy was 100% (95% CI, 17.9%-100.0%) against severe disease and 76.3% (95% CI, 57.4%-86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. CONCLUSIONS: A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. CLINICAL TRIALS REGISTRATION: EudraCT, 2020-004123-16.

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.

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases.

OBJECTIVES: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. RESULTS: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. CONCLUSIONS: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

Evaluation of serious infections, including Mycobacterium tuberculosis, during treatment with biologic disease-modifying antirheumatic drugs: does line of therapy matter?

OBJECTIVES: This study aimed to evaluate if and how the incidence of serious infection (SI) and active tuberculosis (TB) differ among seven biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) considering the line of therapy. METHODS: Patients with RA from the British Society for Rheumatology Biologics Register-RA cohort who initiated etanercept, certolizumab, infliximab, adalimumab, abatacept, rituximab, or tocilizumab from the first to fifth line of therapy were included. Follow-up extended up to three years. Primary outcome was SI, secondary outcome was TB. Event rates were calculated and compared using Cox proportional-hazards, controlling for confounding with inverse probability of treatment weights. Comparisons were made overall and stratified by line of therapy. Sensitivity analysis restricted to all treatment courses from 2009 (tocilizumab availability) until end of study (2018). RESULTS: Among 33 897 treatment courses (62 513 patient-years) the incidence of SI was 4.4/100 patient-years (95%CI 4.2-4.5). After adjustment, hazards ratios (HR) of SI were slightly higher with adalimumab and infliximab compared with etanercept. However, no clear pattern was observed when stratifying by line of therapy, in terms of incidence rate or hazards ratio. Sensitivity analyses showed similar HR among these treatments. Regarding TB, all 49 cases occurred during the first three lines of treatment and rarely since 2009. CONCLUSION: The risk of serious infections does not appear to be influenced by the line of therapy in patients with RA. However, the risk of tuberculosis seems to be more frequent during the initial lines of treatment or prior to 2009.

Treat-to-target urate-lowering therapy and hospitalizations for gout: results from a nationwide cohort study in England.

OBJECTIVE: To investigate associations between treat-to-target urate-lowering therapy (ULT) and hospitalizations for gout. METHODS: Using linked Clinical Practice Research Datalink and NHS Digital Hospital Episode Statistics data, we described the incidence and timing of hospitalizations for flares in people with index gout diagnoses in England from 2004-2020. Using Cox proportional hazards and propensity models, we investigated associations between ULT initiation, serum urate target attainment, colchicine prophylaxis, and the risk of hospitalizations for gout. RESULTS: Of 292 270 people with incident gout, 7719 (2.64%) had one or more hospitalizations for gout, with an incidence rate of 4.64 hospitalizations per 1000 person-years (95% CI 4.54, 4.73). There was an associated increased risk of hospitalizations within the first 6 months after ULT initiation, when compared with people who did not initiate ULT [adjusted Hazard Ratio (aHR) 4.54; 95% CI 3.70, 5.58; P < 0.001]. Hospitalizations did not differ significantly between people prescribed vs not prescribed colchicine prophylaxis in fully adjusted models. From 12 months after initiation, ULT associated with a reduced risk of hospitalizations (aHR 0.77; 95% CI 0.71, 0.83; P < 0.001). In ULT initiators, attainment of a serum urate <360 micromol/l within 12 months of initiation associated with a reduced risk of hospitalizations (aHR 0.57; 95% CI 0.49, 0.67; P < 0.001) when compared with people initiating ULT but not attaining this target. CONCLUSION: ULT associates with an increased risk of hospitalizations within the first 6 months of initiation but reduces hospitalizations in the long term, particularly when serum urate targets are achieved.

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.

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.

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.

Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

OBJECTIVES: The impact of autoantibody profiles on prognosis of idiopathic inflammatory myositis associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with Myositis Specific Antibodies (MSA) remains unclear. This retrospective cohort study examines whether serological profiles are associated with mortality and longitudinal lung function change. METHODS: Baseline clinical/demographic characteristics and follow-up lung function of consecutive adult patients with IIM-ILD or Interstitial Pneumonia with Autoimmune Features (IPAF) positive for MSAs were extracted from three hospitals. Univariate and multi-variate Cox-Proportional Hazards analyses were used to compare mortality between autoantibodies. Regression models were used to analyse lung function trends. RESULTS: Of 430 included patients, 81% met IIM criteria, 19% were IPAF-MSA. On univariate analysis, risk factors associated with mortality included higher age, Charlson Co-morbidity Index and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared to anti-MDA5-negativity, anti-MDA5-positivity (MDA5+) was associated with high mortality in the first 3 months (HR 65.2. 95%CI 14.1, 302.0), while no significant difference was seen thereafter (HR 0.55, 95%CI 0.14, 2.28). On multi-variate analysis, combined anti-synthetase antibodies carried a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in anti-Jo1 + (HR 0.61, 95%CI 0.4-0.87) and increased in anti-PL7+ patients (HR 2.07, 95%CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. CONCLUSIONS: Among autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ confer higher mortality risks. Survivors of an early peak of mortality in anti-MDA5+ disease appear to have a favourable prognosis.