Uptake and safety of pneumococcal vaccination in adults with immune mediated inflammatory diseases: a UK wide observational study.

OBJECTIVE: The uptake and safety of pneumococcal vaccination in people with immune mediated inflammatory diseases (IMIDs) is poorly understood. We investigated the UK wide pneumococcal vaccine uptake in adults with IMIDs and explored the association between vaccination and IMID flare. METHODS: Adults with IMIDs diagnosed on or before 01/09/2018, prescribed steroid-sparing drugs within the last 12 months and contributing data to the Clinical Practice Research Datalink Gold were included. Vaccine uptake was assessed using a cross-sectional study design. Self-controlled case series (SCCS) analysis investigated the association between pneumococcal vaccination and IMID flare. The SCCS observation period was up-to six-month before and after pneumococcal vaccination. This was partitioned into a 14-day pre-vaccination induction, 90-days post-vaccination exposed, and the remaining unexposed periods. RESULTS: We included 32 277 patients, 14 151 with RA, 13 631 with IBD, 3,804 with axial spondyloarthritis and 691 with SLE. Overall, 57% were vaccinated against pneumococcus. Vaccine uptake was lower in those younger than 45 years (32%), with IBD (42%), and without additional indication(s) for vaccination (46%). In the vaccine-safety study, data for 1,067, 935, and 451vaccinated patients with primary-care consultations for joint pain, AIRD flare and IBD flare respectively were included. Vaccination against pneumococcal pneumonia was not associated with primary-care consultations for joint pain, AIRD flare and IBD flare in the exposed period with incidence rate ratios (95% Confidence Interval) 0.95 (0.83-1.09), 1.05 (0.92-1.19), and 0.83 (0.65-1.06) respectively. CONCLUSION: Uptake of pneumococcal vaccination in UK patients with IMIDs was suboptimal. Vaccination against pneumococcal disease was not associated with IMID flare.

Discontinuation of anti-tumour necrosis factor alpha treatment owing to blood test abnormalities, and cost-effectiveness of alternate blood monitoring strategies.

BACKGROUND: There is no evidence base to support the use of 6-monthly monitoring blood tests for the early detection of liver, blood and renal toxicity during established anti-tumour necrosis factor alpha (TNFα) treatment. OBJECTIVES: To evaluate the incidence and risk factors of anti-TNFα treatment cessation owing to liver, blood and renal side-effects, and to estimate the cost-effectiveness of alternate intervals between monitoring blood tests. METHODS: A secondary care-based retrospective cohort study was performed. Data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) were used. Patients with at least moderate psoriasis prescribed their first anti-TNFα treatment were included. Treatment discontinuation due to a monitoring blood test abnormality was the primary outcome. Patients were followed-up from start of treatment to the outcome of interest, drug discontinuation, death, 31 July 2021 or up to 5 years, whichever came first. The incidence rate (IR) and 95% confidence intervals (CIs) of anti-TNFα discontinuation with monitoring blood test abnormality was calculated. Multivariate Cox regression was used to examine the association between risk factors and outcome. A mathematical model evaluated costs and quality-adjusted life years (QALYs) associated with increasing the length of time between monitoring blood tests during anti-TNFα treatment. RESULTS: The cohort included 8819 participants [3710 (42.1%) female, mean (SD) age 44.76 (13.20) years] that contributed 25 058 person-years (PY) of follow-up and experienced 125 treatment discontinuations owing to a monitoring blood test abnormality at an IR of 5.85 (95% CI 4.91-6.97)/1000 PY. Of these, 64 and 61 discontinuations occurred within the first year and after the first year of treatment start, at IRs of 8.62 (95% CI 6.74-11.01) and 3.44 (95% CI 2.67-4.42)/1000 PY, respectively. Increasing age (in years), diabetes and liver disease were associated with anti-TNFα discontinuation after a monitoring blood test abnormality [adjusted hazard ratios of 1.02 (95% CI 1.01-1.04), 1.68 (95% CI 1.00-2.81) and 2.27 (95% CI 1.26-4.07), respectively]. Assuming a threshold of £20 000 per QALY gained, no monitoring was most cost-effective, but all extended periods were cost-effective vs. 3- or 6-monthly monitoring. CONCLUSIONS: Anti-TNFα drugs were uncommonly discontinued owing to abnormal monitoring blood tests after the first year of treatment. Extending the duration between monitoring blood tests was cost-effective. Our results produce evidence for specialist society guidance to reduce patient monitoring burden and healthcare costs.

Is Vaccination Against COVID-19 Associated With Inflammatory Bowel Disease Flare? Self-Controlled Case Series Analysis Using the UK CPRD.

INTRODUCTION: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) flare. METHODS: Patients with IBD vaccinated against COVID-19 who consulted for disease flare between December 1, 2020, and December 31, 2021, were ascertained from the Clinical Practice Research Datalink. IBD flares were identified using consultation and corticosteroid prescription records. Vaccinations were identified using product codes and vaccination dates. The study period was partitioned into vaccine-exposed (vaccination date and 21 days immediately after), prevaccination (7 days immediately before vaccination), and the remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and IBD flares. Season-adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) were calculated using self-controlled case series analysis. RESULTS: Data for 1911 cases with IBD were included; 52% of them were female, and their mean age was 49 years. Approximately 63% of participants had ulcerative colitis (UC). COVID-19 vaccination was not associated with increased IBD flares in the vaccine-exposed period when all vaccinations were considered (aIRR [95% CI] 0.89 [0.77-1.02], 0.79 [0.66-0.95], and 1.00 [0.79-1.27] in IBD overall, UC, and Crohn's disease, respectively). Analyses stratified to include only first, second, or third COVID-19 vaccinations found no significant association between vaccination and IBD flares in the vaccine-exposed period (aIRR [95% CI] 0.87 [0.71-1.06], 0.93 [0.75-1.15], and 0.86 [0.63-1.17], respectively). Similarly, stratification by COVID-19 before vaccination and by vaccination with vectored DNA or messenger RNA vaccine did not reveal an increased risk of flare in any of these subgroups. DISCUSSION: Vaccination against COVID-19 was not associated with IBD flares regardless of prior COVID-19 infection and whether messenger RNA or DNA vaccines were used.

Is vaccination against COVID-19 associated with autoimmune rheumatic disease flare? A self-controlled case series analysis.

OBJECTIVES: To investigate the association between vaccination against coronavirus disease 2019 (COVID-19) and autoimmune rheumatic disease (AIRD) flare. MATERIAL AND METHODS: Patients with AIRDs vaccinated against COVID-19 who consulted for disease flare between 1 December 2020 and 31 December 2021 were ascertained in Clinical Practice Research Datalink (Aurum). AIRD flare was defined as consultation for AIRD with CS prescription on the same day or the next day. Vaccination was defined using date of vaccination and product code. The observation period was partitioned into vaccine-exposed (21 days after vaccination), pre-vaccination (7 days before vaccination) and remaining vaccine-unexposed periods. Participants contributed data with multiple vaccinations and outcomes. Season adjusted incidence rate ratios (aIRR) and 95% CI were calculated using self-controlled case series analysis. RESULTS: Data for 3554 AIRD cases, 72% female, mean age 65 years and 68.3% with RA, were included. COVID-19 vaccination was associated with significantly fewer AIRD flares in the 21-day vaccine-exposed period when all vaccinations were considered [aIRR (95% CI) 0.89 (0.80, 0.98)]. Using dose-stratified analyses there was a statistically significant negative association in the 21 days after first COVID-19 vaccination but no association after the second or third COVID-19 vaccinations [aIRR (95% CI) 0.76 (0.66, 0.89), 0.94 (0.79, 1.11) and 1.01 (0.85, 1.20), respectively]. On AIRD-type stratified analyses, vaccination was not associated with disease flares. Vaccination without or after severe acute respiratory syndrome coronavirus 2 infection, and with vectored DNA or mRNA vaccines, associated with comparable reduced risk of AIRD flares in the vaccine-exposed period after first COVID-19 vaccination. CONCLUSIONS: Vaccination against COVID-19 was not associated with increased AIRD flares regardless of prior COVID-19, AIRD type, and whether mRNA or DNA vaccination technology were used.

COVID-19 infection, admission and death and the impact of corticosteroids among people with rare autoimmune rheumatic disease during the second wave of COVID-19 in England: results from the RECORDER Project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the second wave of the COVID-19 pandemic in England, and describe the impact of corticosteroids on outcomes. METHODS: Hospital Episode Statistics data were used to identify people alive on 1 August 2020 with ICD-10 codes for RAIRD from the whole population of England. Linked national health records were used to calculate rates and rate ratios of COVID-19 infection and death up to 30 April 2021. Primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. NHS Digital and Office for National Statistics general population data were used for comparison. The association between 30-day corticosteroid usage and COVID-19-related death, COVID-19-related hospital admissions and all-cause deaths was also described. RESULTS: Of 168 330 people with RAIRD, 9961 (5.92%) had a positive COVID-19 PCR test. The age-standardized infection rate ratio between RAIRD and the general population was 0.99 (95% CI: 0.97, 1.00). 1342 (0.80%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.76 (95% CI: 2.63, 2.89) times higher than in the general population. There was a dose-dependent relationship between 30-day corticosteroid usage and COVID-19-related death. There was no increase in deaths due to other causes. CONCLUSIONS: During the second wave of COVID-19 in England, people with RAIRD had the same risk of COVID-19 infection but a 2.76-fold increased risk of COVID-19-related death compared with the general population, with corticosteroids associated with increased risk.

The incidence of Kawasaki disease using hospital admissions data for England 2006-2021.

OBJECTIVE: To describe the incidence of Kawasaki Disease (kDa) between 2006 and 2021 in England. METHODS: We identified all cases in hospital episode statistics with an ICD-10 diagnostic code M303 (for kDa) between 1 April 2006 and 31 March 2021. We validated 83 diagnoses using hospital medical records and found >97% accuracy. We calculated incidence rate ratios (IRRs) using Poisson regression and assessed the influence of age, sex, ethnicity and index of multiple deprivation (IMD). We used Office for National Statistics population estimates for England as the denominator. RESULTS: We identified a total of 5908 cases of kDa in all children under the age of 16 (mean age 3.8, s.d.=3.2, 95% CI: 3.7, 3.9). Incidence in children aged <5 years was 8.9 (95% CI: 8.6, 9.2)/100 000 person-years; in children aged 5-9, 2.4 (95% CI: 2.3, 2.6)/100 000 person-years; and in children aged 10-15, 0.6 (95% CI: 0.6, 0.7). Male : female ratio was 1.5 : 1. Incidence was higher among non-White than White ethnicities [adjusted IRR 2.1 (2.0-2.2) for Asian, 3.0 (2.8-3.3) for Black and 4.5 (4.2-4.8) for other ethnicities]. The incidence increased with socioeconomic deprivation; the adjusted IRR of the least deprived IMD quintile compared with the most deprived quintile was 0.81 (0.77-0.84). CONCLUSIONS: Incidence rates of kDa derived from hospital admission data in England were higher than in studies relying on clinician reporting. We confirm previous findings on the influence of sex and ethnicity on kDa incidence and observe that there was a higher incidence of kDa within more deprived socioeconomic groups.

Predicting Need for Escalation of Care or Death From Repeated Daily Clinical Observations and Laboratory Results in Patients With Severe Acute Respiratory Syndrome Coronavirus 2.

We compared the performance of prognostic tools for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using parameters fitted either at the time of hospital admission or across all time points of an admission. This cohort study used clinical data to model the dynamic change in prognosis of SARS-CoV-2 at a single hospital center in the United Kingdom, including all patients admitted from February 1, 2020, to December 31, 2020, and then followed up for 60 days for intensive care unit (ICU) admission, death, or discharge from the hospital. We incorporated clinical observations and blood tests into 2 time-varying Cox proportional hazards models predicting daily 24- to 48-hour risk of admission to the ICU for those eligible for escalation of care or death for those ineligible for escalation. In developing the model, 491 patients were eligible for ICU escalation and 769 were ineligible for escalation. Our model had good discrimination of daily risk of ICU admission in the validation cohort (n = 1,141; C statistic: C = 0.91, 95% confidence interval: 0.89, 0.94) and our score performed better than other scores (National Early Warning Score 2, International Severe Acute Respiratory and Emerging Infection Comprehensive Clinical Characterisation Collaboration score) calculated using only parameters measured on admission, but it overestimated the risk of escalation (calibration slope = 0.7). A bespoke daily SARS-CoV-2 escalation risk prediction score can predict the need for clinical escalation better than a generic early warning score or a single estimation of risk calculated at admission.

Population-based cohort study of the efficacy of brentuximab vedotin in relapsed systemic anaplastic large-cell lymphoma using Public Health England data.

Systemic anaplastic large-cell lymphoma (sALCL) is a rare T-cell lymphoma associated with poor prognosis after relapse. The immunoconjugate brentuximab vedotin (BV) first became available for relapsed sALCL in England in 2013, following the results of a pivotal phase II study. We present a population-based study describing outcomes of relapsed sALCL in England after BV, using Public Health England data. We obtained information on all relapsed/refractory (r/r) sALCL patients ≥18 years treated with BV monotherapy in England between 1 January 2014 and 31 December 2019. The final cohort comprised 127 patients with a median age of 60 years (range 19-89). Eighteen (14·2%) had received stem cell transplant in first remission. Median two-year overall survival (OS) was 46·6%. The vast majority of deaths (59) occurred within 18 months, with very few events after this. Receipt of BV as second line compared to third or fourth line was associated with significantly improved survival (two-year OS 50·3% vs 29·7%, P = 0·03). There was no difference in OS for different subgroups, including anaplastic lymphoma kinase status, age, gender, or receipt of stem cell transplantation in first response. We report excellent survival following treatment with BV in a real-world setting, comparable with previous clinical trial data.

COVID-19 infection, admission and death among people with rare autoimmune rheumatic disease in England: results from the RECORDER project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population. METHODS: We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. RESULTS: We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30-2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. CONCLUSIONS: During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.

Development and validation of a prognostic model for leflunomide discontinuation with abnormal blood tests during long-term treatment: cohort study using data from the Clinical Practice Research Datalink Gold and Aurum.

OBJECTIVE: To develop and validate a prognostic model for LEF discontinuation with abnormal blood test results. METHODS: Data from the Clinical Practice Research Datalink Gold and Aurum were used for model development and external validation, respectively. Participants prescribed LEF between 1 January 2007 and 31 December 2019 were followed up from 6 months after the first general practitioner prescription to the earliest of date of outcome, death, 5 year follow-up or 31 December 2019. Candidate prognostic factors were ascertained using theory and data-driven approaches. Penalized Cox regression was performed to develop the risk equation, followed by internal validation using 500 bootstraps to correct for optimism. Multiple imputation was applied to handle missing data. Model performance was assessed in terms of calibration and discrimination. RESULTS: Data for 1487 and 2329 participants contributing 3140 and 5246 person-years follow-up were included in the development and validation cohorts, respectively. Thirteen candidate predictors were included in the model. Epilepsy and either cytopenia or elevated liver enzymes during the first 6 months of shared-care LEF prescription were strong predictors of drug discontinuation with a hazard ratio of 4.39 (95% CI 1.74, 11.06) and 3.06 (2.15, 4.35), respectively. The unadjusted and optimism-adjusted calibration slope in development data was 1.00 (95% CI 0.75, 1.25) and 0.72 (95% CI 0.47, 0.97), respectively. The calibration slope in validation data was 0.91 (95% CI 0.74, 1.07). The model showed prognostic separation with an optimism-adjusted Royston D statistic of 0.73 (95% CI 0.44, 1.02). CONCLUSION: We have developed and externally validated an easy-to-use prognostic model that may be used to risk stratify monitoring for LEF toxicity and to make informed choices about risks when choosing treatments.

Improved survival outcomes despite older age at diagnosis: an era-by-era analysis of patients with primary central nervous system lymphoma treated at a single referral centre in the United Kingdom.

Observational studies with long-term follow-up of patients with primary central nervous system lymphoma (PCNSL) are scarce. Patient data over a period of four decades were retrospectively analysed from databases at Nottingham University Hospitals Trust, UK. The cohort was delineated by two distinct therapeutic eras; the first from 01/01/1982 to 31/12/2010 (n = 147) and the second 01/01/2011 to 31/07/2020 (n = 125). The median age at diagnosis was significantly older in the second era compared to the first (69 and 65 years respectively, P = 0·003). The 3-, 6- and 12-month overall survival (OS) rates in the second era were significantly higher compared to the first, at 85%, 77%, 62% versus 56%, 49%, 38% respectively (log-rank test P < 0·0001). On multivariate analysis, high-dose methotrexate (HD-MTX)-based induction protocols employed in the second era were associated with improved OS compared to those used in the first [hazard ratio (HR) 0·40, 95% confidence interval (CI) 0·28-0·57]. Within the second era, superior OS rates were seen with the use of intensive HD-MTX protocols (including consolidation with high-dose chemotherapy and autologous stem cell transplantation) compared to non-intensive HD-MTX schedules (HR 0·47, 95% CI 0·22-0·99). Initiating chemotherapy within 14 days of biopsy and use of rituximab were independently associated with improved OS and progression-free survival during the second era. These data suggest that prompt treatment initiation and use of intensive HD-MTX- and rituximab-based protocols have resulted in improved survival outcomes for patients.

A systematic review and meta-analysis of the incidence rate of Takayasu arteritis.

OBJECTIVES: Takayasu arteritis (TAK) is a rare autoimmune rheumatic disease causing large-vessel vasculitis. Onset is typically between the ages of 20 and 30 years. It is associated with substantial morbidity and mortality, notably due to its effects on the cardiovascular system. It has a poorly understood global epidemiology. Our objective was to systematically review the available evidence in order to calculate the incidence rate of TAK. METHODS: Three databases (MEDLINE, PubMed and Embase) were searched in November 2019 and the results were screened by two reviewers. A random effects meta-analysis was then conducted in R to calculate the overall incidence rate. Heterogeneity was assessed using I2. The quality of the studies was assessed using an adapted Newcastle-Ottawa scale. Further subgroup analyses were performed by quality, sex, research setting and geographical location. Publication bias was assessed using a Begg's funnel plot. RESULTS: The incidence rate for TAK was 1.11 per million person-years (95% CI 0.70-1.76). The heterogeneity in the data was extremely high in all analyses, which suggests that there was considerable variation in incidence rates across the different populations studied. TAK was found to be more common in women (incidence rate 2.01 per million person-years, 95% CI 1.39-2.90). CONCLUSIONS: TAK is an extremely rare disease. It affects women more commonly than men. There is considerable variation in the incidence rate between populations. We suggest that future research should focus on discrete populations in order to better identify genetic and environmental risk factors.

ß-blocker prescription is associated with lower cumulative risk of knee osteoarthritis and knee pain consultations in primary care: a propensity score-matched cohort study.

OBJECTIVES: To examine the association between ß-blocker prescription and first primary-care consultation for knee OA, hip OA, knee pain and hip pain. METHODS: Data source: Clinical Practice Research Datalink. Participants aged ≥40 years in receipt of new oral ß-blocker prescriptions were propensity score (PS) matched to an unexposed control. Cox proportional hazard ratios (HRs) and 95% CIs were calculated, and adjusted for non-osteoporotic fractures, number of primary-care consultations for knee or hip injury, and, the number of primary-care consultations, out-patient referrals and hospitalizations in the 12 months preceding cohort entry. Analysis was stratified according to ß-blocker class and for commonly prescribed drugs. P < 0.05 was considered statistically significant. RESULTS: A total of 111 718 ß-blocker-exposed participants were 1:1 PS matched to unexposed controls. ß-blocker prescription was associated with reduced cumulative risk of knee OA, knee pain, and hip pain consultations [with a HR (95% CI) of 0.90 (0.83, 0.98), 0.88 (0.83, 0.92) and 0.85 (0.79, 0.90), respectively]. Propranolol and atenolol were associated with a lower incidence of knee OA and knee pain consultations with a HR of between 0.78 and 0.91. ß-blockers were associated with reduced incidence of consultation for large-joint lower-limb OA/pain as a composite outcome, defined as the earliest of knee OA, knee pain, hip OA or a hip pain consultation [with a HR (95% CI) of 0.87 (0.84, 0.90)]. CONCLUSION: Commonly used ß-blockers have analgesic properties for musculoskeletal pain. Atenolol might be a therapeutic option for OA and cardiovascular co-morbidities in which ß-blockers are indicated, while propranolol may be suitable for people with co-morbid anxiety. A confirmatory randomized controlled trial is needed before clinical practice is changed.

What is the incidence of methotrexate or leflunomide discontinuation related to cytopenia, liver enzyme elevation or kidney function decline?

OBJECTIVES: To examine incidence of treatment changes due to abnormal blood-test results and, to explore rates of treatment changes due to liver, kidney and haematological blood-test abnormalities in autoimmune rheumatic diseases (AIRD) treated with low-dose MTX or LEF. METHODS: Data for people with AIRDs prescribed MTX or LEF were extracted from the Clinical Practice Research Datalink. Participants were followed-up from first prescription of MTX or LEF in primary care. Primary outcome of interest was drug discontinuation, defined as a prescription gap of ≥90 days following an abnormal (or severely abnormal) blood-test result. Dose reduction was examined between consecutive prescriptions. Incidence rates per 1000 person-years were calculated. RESULTS: 15, 670 and 2,689 participants contributing 46, 571 and 4,558 person-years follow-up were included in MTX and LEF cohorts, respectively. The incidence of MTX and LEF discontinuation with abnormal (severely abnormal) blood-test was 42.24 (6.16) and 106.53 (9.42)/1000 person-years in year 1, and 22.44 (2.84) and 31.69 (4.40)/1000 person years, respectively, thereafter. The cumulative incidence of MTX and LEF discontinuation with abnormal (severely abnormal) blood tests was 1 in 24 (1 in 169), 1 in 9 (1 in 106) at 1 year; and 1 in 45 (1 in 352), 1 in 32 (1 in 227) per-year, respectively, thereafter. Raised liver enzymes were the commonest abnormality associated with drug discontinuation. MTX and LEF dose reduction incidence were comparable in year 1, however, thereafter MTX dose was reduced more often than LEF [16.60 (95% CI 13.05, 21.13) vs 8.10 (95% CI 4.97, 13.20)/1000 person-years]. CONCLUSION: MTX and LEF were discontinued for blood-test abnormalities after year 1 of treatment, however, discontinuations for severely abnormal results were uncommon.

Risk of death among people with rare autoimmune diseases compared with the general population in England during the 2020 COVID-19 pandemic.

OBJECTIVES: To quantify the risk of death among people with rare autoimmune rheumatic diseases (RAIRD) during the UK 2020 COVID-19 pandemic compared with the general population, and compared with their pre-COVID risk. METHODS: We conducted a cohort study in Hospital Episode Statistics for England from 2003 onwards, and linked data from the NHS Personal Demographics Service. We used ONS published data for general population mortality rates. RESULTS: We included 168 691 people with a recorded diagnosis of RAIRD alive on 1 March 2020. Their median age was 61.7 (IQR 41.5-75.4) years, and 118 379 (70.2%) were female. Our case ascertainment methods had a positive predictive value of 85%. A total of 1815 (1.1%) participants died during March and April 2020. The age-standardized mortality rate (ASMR) among people with RAIRD (3669.3; 95% CI: 3500.4, 3838.1 per 100 000 person-years) was 1.44 (95% CI: 1.42, 1.45) times higher than the average ASMR during the same months of the previous 5 years, whereas in the general population of England it was 1.38 times higher. Age-specific mortality rates in people with RAIRD compared with the pre-COVID rates were higher from the age of 35 upwards, whereas in the general population the increased risk began from age 55 upwards. Women had a greater increase in mortality rates during COVID-19 compared with men. CONCLUSION: The risk of all-cause death is more prominently raised during COVID-19 among people with RAIRD than among the general population. We urgently need to quantify how much risk is due to COVID-19 infection and how much is due to disruption to health-care services.

Effectiveness of inactivated influenza vaccine in autoimmune rheumatic diseases treated with disease-modifying anti-rheumatic drugs.

OBJECTIVES: The effectiveness of inactivated influenza vaccine in people with autoimmune rheumatic disease (AIRDs) is not known. We investigated whether the influenza vaccine is effective in preventing respiratory morbidity, mortality and all-cause mortality in AIRD patients. METHODS: Adults with AIRDs treated with DMARDs prior to 1 September of each year between 2006 and 2009, and 2010 and 2015 were identified from the Clinical Practice Research Datalink. Exposure and outcome data were extracted. Data from multiple seasons were pooled. Propensity score (PS) for vaccination was calculated. Cox-proportional hazard ratios (HRs) and 95% CIs were calculated, and were (i) adjusted, (ii) matched for PS for vaccination. RESULTS: Data for 30 788 AIRD patients (65.7% female, 75.5% with RA, 61.1% prescribed MTX) contributing 125 034 influenza cycles were included. Vaccination reduced risk of influenza-like illness [adjusted HR (aHR) 0.70], hospitalization for pneumonia (aHR 0.61) and chronic obstructive pulmonary disease exacerbations (aHR 0.67), and death due to pneumonia (aHR 0.56) on PS-adjusted analysis in the influenza active periods (IAPs). The associations were of similar magnitude and remained statistically significant on PS-matched analysis except for protection from influenza-like illness, which became non-significant. Sub-analysis restricted to pre-IAP, IAP and post-IAP did not yield evidence of residual confounding on influenza-like illness and death due to pneumonia. Vaccination reduced risk of all-cause mortality, although IAP-restricted analysis demonstrated residual confounding for this outcome. CONCLUSION: Influenza vaccine associates with reduced risk of respiratory morbidity and mortality in people with AIRDs. These findings call for active promotion of seasonal influenza vaccination in immunosuppressed people with AIRDs by healthcare professionals.

Association between inactivated influenza vaccine and primary care consultations for autoimmune rheumatic disease flares: a self-controlled case series study using data from the Clinical Practice Research Datalink.

ObjectivesTo examine the association between inactivated influenza vaccine (IIV) administration and primary care consultation for joint pain, rheumatoid arthritis (RA) flare, corticosteroid prescription, vasculitis and unexplained fever in people with autoimmune rheumatic diseases (AIRDs). METHODS: We undertook within-person comparisons using self-controlled case-series methodology. AIRD cases who received the IIV and had an outcome of interest in the same influenza cycle were ascertained in Clinical Practice Research Datalink. The influenza cycle was partitioned into exposure periods (1-14 days prevaccination and 0-14, 15-30, 31-60 and 61-90 days postvaccination), with the remaining time-period classified as non-exposed. Incidence rate ratios (IRR) and 95% CI for different outcomes were calculated. RESULTS: Data for 14 928 AIRD cases (69% women, 80% with RA) were included. There was no evidence for association between vaccination and primary care consultation for RA flare, corticosteroid prescription, fever or vasculitis. On the contrary, vaccination associated with reduced primary care consultation for joint pain in the subsequent 90 days (IRR 0.91 (95% CI 0.87 to 0.94)). CONCLUSION: This study found no evidence for a significant association between vaccination and primary care consultation for most surrogates of increased disease activity or vaccine adverse-effects in people with AIRDs. It adds to the accumulating evidence to support influenza vaccination in AIRDs.

Temporal relationships between systemic lupus erythematosus and comorbidities.

OBJECTIVE: To examine the burden of comorbidities prior to and after the diagnosis of SLE and its impact on mortality. METHODS: We identified 1605 incident cases of SLE and 6284 matched controls from the UK primary care. The risks of comorbidities before (prevalence; odds ratios) and after SLE diagnosis (incidence; hazard ratios) and the impact of comorbidities at diagnosis on all-cause mortality were estimated. RESULTS: At diagnosis, SLE was associated with adjusted odds ratios (95% CI) of 2.25 (1.97-2.56), 3.37 (2.49-4.57) and 3.54 (1.89-6.63) for a Charlson comorbidity index of 1-2, 3-4 and ≥5, respectively. Following diagnosis, SLE also associated with increased risk of developing any comorbidity with an adjusted hazard ratio (95% CI) of 1.30 (95% CI, 1.13-1.49). At diagnosis, SLE was associated with a greater risk of cancer, cardiovascular, renal, liver, rheumatological and neurological diseases as well as depression, anaemia and psoriasis. Risks of developing incident comorbidity in the categories of neoplasm, cardiovascular, genitourinary, metabolic/endocrine, gastrointestinal and hepatic diseases, chronic pulmonary diseases, musculoskeletal/connective tissue and neurological diseases were higher in SLE patients. People with SLE had higher mortality risk compared with controls, with adjusted hazard ratio of 1.91 (95% CI, 1.62-2.26); after further adjusting for comorbidities this reduced to 1.64 (1.37-1.97). Comorbidities at SLE diagnosis accounted for 27.6% of the apparent difference in mortality between SLE patients and matched controls. CONCLUSION: People with SLE have increased risks of multiple comorbidities both prior to and after diagnosis and this contributes significantly to all-cause mortality.

Novel insights into the aetiology of granulomatosis with polyangiitis-a case-control study using the Clinical Practice Research Datalink.

Objectives: We aimed to provide insights into the aetiology of granulomatosis with polyangiitis (GPA), by conducting a large case-control study using a general population-based, prospectively collected database of healthcare records. Methods: We compared all incident cases of GPA in the Clinical Practice Research Datalink 1990-2014, with up to 10 age-, sex- and general practice-matched controls. We identified potential risk factors, recorded numbers of cases and controls exposed to each, and calculated odds ratios (ORs) using conditional logistic regression. Our main analysis excluded data recorded during 1 year before diagnosis, to prevent early symptoms being mistaken for risk factors. Results: We identified 757 people with GPA and matched 7546 controls. People with GPA were five times more likely to have a previous diagnosis of bronchiectasis (OR = 5.1, 95% CI: 2.7, 9.4; P < 0.0001), and these effects remained stable in diagnoses recorded >5 years prior to diagnosis. People with GPA were two to three times more likely than controls to have previous diagnoses of autoimmune diseases or chronic renal impairment, and these effects also remained stable >5 years prior to diagnosis. People with GPA were more likely to have a diagnosis of pulmonary fibrosis (OR = 5.7, 95% CI: 1.7, 19.5; P = 0.01) and sinus infections (OR = 2.7, 95% CI: 1.8, 4.2; P < 0.0001) recorded in the 3 years before diagnosis, but not before this. We also found former smoking, some medications and higher socio-economic status significantly, but less strongly, associated. Conclusion: We found novel long-term associations between GPA and pre-existing bronchiectasis and autoimmune diseases.