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.

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.

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.

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.

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.

The association between lymphopenia and serious infection risk in rheumatoid arthritis.

OBJECTIVES: To investigate the relationship between occurrence of serious infection (SI) and lymphocyte counts in patients with RA using data from a single centre. METHODS: We used routinely captured data from a single tertiary rheumatology centre to explore the relationship between lymphopenia and SI risk. Adult RA patients were included over a 5-year follow-up period. Admissions due to confirmed SI were considered. SI rate with 95% confidence intervals was calculated. The association between SI with baseline lymphocyte counts, time-averaged lymphocyte counts throughout all follow-up, and a nadir lymphocyte count was assessed using Cox proportional hazards regression. The relationship between lymphopenia over time and SI was analysed using a mixed-effect model of lymphocyte counts prior to SI. RESULTS: This analysis included 1095 patients with 205 SIs during 2016 person-years of follow-up. The SI rate was 4.61/100 patient-years (95% CI: 3.76, 5.65). Compared with patients with nadir lymphocyte counts >1.5 × 109 cells/l, nadir lymphopenia <1 × 109 cells/l was significantly associated with higher SI risk (HR 3.28; 95% CI: 1.59, 6.76), increasing to HR 8.08 (95% CI: 3.74, 17.44) in patients with lymphopenia <0.5 × 109 cells/l. Lymphocyte counts were observed to be reduced in the 30-day period prior to SI. CONCLUSION: Lymphocyte counts below <1.0 × 109 cells/l were associated with higher SI risk in RA patients; the strongest association between lymphopenia and SI was observed when lymphocyte counts were below <0.5 × 109 cells/l. Lymphopenia may be used as a measure to stratify patients at risk of SI.

Polypharmacy is associated with treatment response and serious adverse events: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

OBJECTIVE: To evaluate whether polypharmacy is associated with treatment response and serious adverse events (SAEs) in patients with RA using data from the British Society for Rheumatology Biologics Register (BSRBR-RA). METHODS: The BSRBR-RA is a prospective observational cohort study of biologic therapy starters and a DMARD comparator arm. A logistic regression model was used to calculate the odds of a EULAR 'good response' after 12 months of biologic therapy by medication count. Cox proportional hazards models were used to identify risk of SAEs. The utility of the models were compared with the Rheumatic Disease Comorbidity Index using Receiver Operator Characteristic and Harrell's C statistic. RESULTS: The analysis included 22 005 patients, of which 83% were initiated on biologics. Each additional medication reduced the odds of a EULAR good response by 8% [odds ratios 0.92 (95% CI 0.91, 0.93) P < 0.001] and 3% in the adjusted model [adjusted odds ratios 0.97 (95% CI 0.95, 0.98) P < 0.001]. The Receiver Operator Characteristic demonstrated significantly greater areas under the curve with the polypharmacy model than the Rheumatic Disease Comorbidity Index. There were 12 547 SAEs reported in 7286 patients. Each additional medication equated to a 13% increased risk of an SAE [hazard ratio 1.13 (95% CI 1.12, 1.13) P < 0.001] and 6% in the adjusted model [adjusted hazard ratio 1.06 (95% CI 1.05, 1.07) P < 0.001]. Predictive values for SAEs were comparable between the polypharmacy and Rheumatic Disease Comorbidity Index model. CONCLUSION: Polypharmacy is a simple but valuable predictor of clinical outcomes in patients with RA. This study supports medication count as a valid measure for use in epidemiologic analyses.

Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

OBJECTIVES: To compare the incidence of serious infection (SI) across biologic drugs used to treat rheumatoid arthritis (RA) using data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA). METHODS: The BSRBR-RA is a prospective observational cohort study. This analysis included patients with RA starting a new biologic. The primary outcome was SI defined as an infectious event requiring admission to hospital, intravenous antibiotics or resulting in death. Event rates were calculated and compared across biologics using Cox proportional hazards with adjustment for potential confounders. Secondary outcomes were the rate of infection by organ class and 30-day mortality following infection. RESULTS: This analysis included 19 282 patients with 46 771 years of follow-up. The incidence of SI was 5.51 cases per 100 patient years for the entire cohort (95% CI 5.29 to 5.71). Compared with etanercept, tocilizumab had a higher risk of SI (HR 1.22, 95% CI 1.02 to 1.47) and certolizumab pegol a lower risk of SI (HR 0.75, 95% CI 0.58 to 0.97) in the fully adjusted model. The 30-day mortality following SI was 10.4% (95% CI 9.2% to 11.6%). CONCLUSIONS: The rate of SI was lower with certolizumab pegol than etanercept in the primary analysis but the result was no longer significant in several sensitivity analyses performed suggesting residual confounding may account for the observed difference. From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of SI than other biologics; however, the risk does not appear to be significantly higher as has previously been suggested.

Opportunistic infections in rheumatoid arthritis patients exposed to biologic therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

Objectives: This analysis set out to estimate the risk of opportunistic infection (OI) among patients with RA by biologic class. Methods: The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis is a prospective observational cohort study established to evaluate safety of biologic therapies. The population included adults commencing biologic therapy for RA. The primary outcome was any serious OI excluding tuberculosis (TB). Event rates were compared across biologic classes using Cox proportional hazards with adjustment for potential confounders identified a priori. Analysis of the incidence of TB was performed separately. Results: In total, 19 282 patients with 106 347 years of follow-up were studied; 142 non-TB OI were identified at a rate of 134 cases/100 000 patient years (pyrs). The overall incidence of OI was not significantly different between the different drug classes; however, the rate of Pneumocystis infection was significantly higher with rituximab than with anti-TNF therapy (adjusted hazard ratio = 3.2, 95% CI: 1.4, 7.5). The rate of TB fell dramatically over the study period (783 cases/100 000 pyrs in 2002 to 38 cases/100 000 pyrs in 2015). The incidence of TB was significantly lower among rituximab users than anti-TNF users, with 12 cases/100 000 pyrs compared with 65 cases/100 000 pyrs. Conclusions: The overall rate of OI was not significantly different between drug classes; however, a subtle difference in the pattern of OI was seen between the cohorts. Patient factors such as age, gender and comorbidity were the most important predictors of OI.

Biologic prescribing decisions following serious infection: results from the British Society for Rheumatology Biologics Register-Rheumatoid Arthritis.

Objectives: To establish whether the decision to stop, continue or switch TNF inhibitor (TNFi) therapy to a biologic drug with an alternative mode of action following a serious infection (SI) impacts upon the risk of recurrent SI in patients with RA. Methods: Patients recruited to the British Society for Rheumatology Biologics Register-RA with at least one episode of SI while on TNFi were included. The biologic treatment decision following SI was considered. A multivariable adjusted Cox proportional hazards model was used to identify predictors of recurrent SI and whether biologic treatment choices influenced future SI risk. Results: In total, 1583 patients suffered at least one SI while on TNFi. Most patients (73%) were recorded as continuing TNFi 60 days after an index SI. The rate of recurrent SI was 25.6% per annum (95% CI: 22.5, 29.2%). The rate of recurrent SI was highest in patients who stopped their TNFi (42.6% per annum, 95% CI: 32.5, 55.7%) and lowest in those who switched biologic drug class (12.1% per annum, 95% CI: 3.9, 37.4%). Compared with patients stopping biologic therapy, patients who continued or switched drug class had significantly lower risk of recurrent SI (drug continuation hazard ratio = 0.54, 95% CI: 0.40, 0.74; drug switch hazard ratio = 0.29, 95% CI: 0.09, 0.95). Conclusions: Patients who continued or switched their TNFi post-index SI had a lower risk of recurrent SI infection compared with those who stopped the drug. This may be explained by better control of disease activity with reintroduction of biologic therapy, a driving factor for SI or alternatively channelling fitter patients to restart biologic therapy.

Recurrent serious infections in patients with rheumatoid arthritis-results from the British Society for Rheumatology Biologics Register.

Objectives: To establish the rate of recurrent infection in RA patients recruited to the British Society for Rheumatology Biologics Register - Rheumatoid Arthritis. Secondary objectives were to establish whether the organ class of index infection predicted future serious infection (SI). Methods: Using data from the British Society for Rheumatology Biologics Register - Rheumatoid Arthritis, a prospective observational cohort, we identified patients with at least one episode of SI. Incidence rates of SI, recurrent SI within the same organ class as the index infection and recurrent SI (of any class) were calculated. A Cox proportional hazards model was used to identify predictors of SI. Results: In total, 5289 subjects with at least one SI contributing 19 431 patient-years follow-up were studied. The baseline annual rate of first SI was 4.6% (95% CI: 4.5, 4.7), increasing to 14.1% (95% CI: 13.5, 14.8) following an index infection. Respiratory infections were the most frequent (44% of all events). Recurrent infections mirrored the organ class of the index infection. Sepsis, increasing age and polypharmacy were significant predictors of infection recurrence in a fully adjusted model. The system class of index infection was associated with the risk of a recurrent event; subjects who experienced sepsis had the highest risk of subsequent SI within 12 months, 19.7% (95% CI: 15.1, 25.7). Conclusion: Recurrent infections in RA are common. Understanding patterns and predictors of recurrent infection together with the differential infection risk associated with immunosuppressive agents will help personalize RA care, tailor treatment choices better and mitigate against episodes of SI.

Differentiating Disease Flare From Infection: A Common Problem in Rheumatology. Do 18F-FDG PET/CT Scans and Novel Biomarkers Hold The Answer?

PURPOSE OF REVIEW: Fever is common within rheumatology but it is often challenging to identify its source. To do so correctly is paramount in patients with an underlying inflammatory condition receiving immunosuppressive therapy. This review article looks at the available evidence and merits of both 18F-fluoro-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans and new proposed biomarkers in determining the cause of fever within rheumatology. RECENT FINDINGS: 18F-FDG PET/CT scans are already an established tool in the detection and diagnosis of malignancy and are emerging for use in fever of unknown origin. More recently, they have been used to identify rheumatological causes of fever such as large vessel vasculitis and adult-onset Still's disease. Within these conditions, biomarkers such as procalcitonin and presepsin may help to differentiate endogenous from exogenous pyrogens. 18F-FDG PET/CT scanning shows promise in locating the source of pyrogens and may be superior to other conventional forms of imaging. As evidence and test availability increases, its use is likely to become commonplace in the diagnostic work-up of fever. Once a source is located, selected biomarkers may be used to confirm a cause.

A population study of the reported incidence of native joint septic arthritis in the United Kingdom between 1998 and 2013.

OBJECTIVES: Septic arthritis is a life-threatening condition with mortality rates of 10-15%. Previous studies in other countries have shown the incidence of septic arthritis may be changing. Our aim was investigate the incidence and pattern of native joint septic arthritis in the UK. METHODS: We performed an analysis using Hospital Episode Statistics to investigate the reported incidence of septic arthritis in the UK between 1998 and 2013. RESULTS: A total of 54 532 cases of septic arthritis were reported via Hospital Episode Statistics during the timeframe studied. There has been a 43% increase in the reported incidence of septic arthritis, with rates rising from 5.5/100 000 in 1998 to 7.8/100 000 in 2013. The rate increased most rapidly in those >75 years of age (15/100 000 in 1998 and 31/100 000 in 2013). Staphylococcal species were the most frequently reported, followed by Streptococcus Pneumococcus rates were relatively stable, with the exception of a 7-fold spike in reported incidence in 2011. DISCUSSION: This large population-based study demonstrates that the incidence of septic arthritis is increasing in the UK. Rates are increasing most rapidly in the >75 years age group, which is likely the result of increasing co-morbidities. The clustering of pneumococcal cases has potential public health implications.

A large two-centre study in to rates of influenza and pneumococcal vaccination and infection burden in rheumatoid arthritis in the UK.

BACKGROUND: Infections are a common complication of RA with associated morbidity and mortality. The aetiology of increased risk is complex and multifactorial. Despite this, strategies to mitigate against risk of infection including vaccination are not always addressed in primary or secondary care with wide variation in practice from multiple small single centre audits. This study was a large two-centre survey of vaccine uptake in routine clinical practice and evaluated the relationship between vaccination and the burden of infection in RA patients. METHODS: A patient questionnaire was devised and disseminated through postal, clinic and phone survey at 2 UK rheumatology centres, detailing past vaccination history, reasons for non-vaccination, and history of recent infection. In a subset of patients, primary care vaccination data were also obtained. RESULTS: In total 929 patients responded to the survey. Over 85 % of patients were vaccinated against influenza, however only 44 % were vaccinated against pneumococcus. The vast majority of vaccination was undertaken in primary care. In the 12 months prior to the survey, 7.7 % of subjects recalled at least one episode of severe infection requiring admission, and nearly 40 % reported receiving at least one course of antibiotics. CONCLUSIONS: Infections are common in RA and Rheumatologists need to be adept at recognising at risk patients and managing them appropriately. Influenza vaccination uptake is good whilst pneumococcal vaccination rates are comparatively poor. Collaborative approaches between primary and secondary care are required to maximise vaccine uptake, which is safe and recommended in RA patients.

The effect of subclinical ketosis on activity at estrus and reproductive performance in dairy cattle.

Our aims were to investigate the influence of subclinical ketosis (SCK) on physical activity at estrus using a neck accelerometer device and on future reproductive performance. Two hundred three Holstein-Friesian cows were studied on 3dairy farms in Northwest England between September 2013 and March 2014. Seventeen percent (35 of 203) of the enrolled cows were affected with SCK between 7 and 21d in milk, defined as a blood ß-hydroxybutyrate concentration of 1.2 to 2.9mmol/L. Time to event analyses and multivariable regression analyses were used to assess the effect of SCK on reproductive performance and activity at estrus. The SCK cows exhibited a lower peak activity (measured as the number of standard deviations above mean activity) and shorter duration in activity clusters associated with first estrus and first insemination postpartum, compared with non-SCK cows. Peak activity and cluster duration associated with the insemination that led to a pregnancy were not different between SCK and non-SCK cows. Calving to first estrus, calving to first insemination, and calving to pregnancy intervals were prolonged in SCK cows. First insemination was 4.3 times (95% confidence interval=1.6 to 15.0) less likely to be successful in SCK cows compared with non-SCK cows. Adjusted mean number of inseminations per pregnancy was 2.8 for SCK cows and 2.0 for non-SCK cows. The current study confirms the long-lasting effects of SCK on reproductive efficiency. Furthermore, it is indicated that physical activity around estrus is reduced by SCK in early lactation, but this negative effect appears to diminish as cows progress through lactation.

No Waning of Pneumococcal Vaccine Responses over Time in People with Inflammatory Arthritis: Findings from a Single Centre Cohort.

BACKGROUND: Vaccination against pneumococcus reduces the risk of infective events, hospitalisation, and death in individual with inflammatory arthritis, particularly in those on immunomodulating therapy who are at risk of worse outcomes from pneumococcal disease. The objective of this study was to investigate the serological protection following vaccination against pneumococcal serovars over time. Methods: This was a single centre, retrospective cohort study of individuals with rheumatoid arthritis, psoriatic arthritis, or axial spondylarthritis who had previously received the PPSV23 polysaccharide pneumococcal vaccine (Pneumovax). Data were retrieved between January 2021 to August 2023. Dates of previous pneumococcal vaccination were identified using linked primary care records. Serum serotype levels were collected. The primary outcome was serological response defined as a titre ≥0.35 mcg/mL in at least five from a total of 12 evaluated pneumococcal serovars, examined using a Luminex platform. Multivariate logistic regression models adjusting for age, gender, ethnicity, co-morbidities, and the use of prednisolone, conventional synthetic and biological DMARDs were used to determine the odds of a sustained serological response according to time categorised into ≤5 years, 5-10 years, and ≥10 years since vaccination. Results: Serological response was measured in 296 individuals with inflammatory arthritis, with rheumatoid arthritis the most common diagnosis (74% of patients). The median time between pneumococcal vaccine administration and serological assessment was 6 years (interquartile range 2.4 to 9.9). A positive serological response to at least 5 serovars was present in 195/296 (66%) of patients. Time since vaccination did not significantly associate with serological protection compared with those vaccinated <5 years, the adjusted ORs of vaccine response was 1.15 (95% CI 0.64 to 2.07) in those 5-10 years and 1.26 (95% CI: 0.64 to 2.48) in those vaccinated over 10 years ago. No individual variable from the multivariate model reached statistical significance as an independent predictor of vaccine response, although steroid use at the time of vaccine had a consistent detrimental impact on serological immunity. Conclusions: We demonstrated that antibody titres following vaccination against pneumococcal serovars do not appear to wane over time. It appears more critical to focus on maximising the initial vaccine response, which is known to be diminished in this patient population.

Endocrine abnormalities in Townes-Brocks syndrome.

Townes-Brocks syndrome is a recognizable variable pattern of malformation caused by mutations to the SALL1 gene located on chromosome 16q12.1. Only three known cases of Townes-Brocks syndrome with proven SALL1 gene mutation and concurrent endocrine abnormalities have been previously documented to our knowledge [Kohlhase et al., 1999; Botzenhart et al., 2005; Choi et al., 2010]. We report on two unrelated patients with Townes-Brocks syndrome who share an identical SALL1 mutation (c.3414_3415delAT), who also have endocrine abnormalities. Patient 1 appears to be the first known case of growth hormone deficiency, and Patient 2 extends the number of documented mutation cases with hypothyroidism to four. We suspect endocrine abnormalities, particularly treatable deficiencies, may be an underappreciated component to Townes-Brocks syndrome.

A Systematic Review and Meta-Analysis of Anti-Rheumatic Drugs and Pneumococcal Vaccine Immunogenicity in Inflammatory Arthritis.

BACKGROUND: Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute for Health and Care Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our objective was to compare the chance of a seroconversion following vaccination against pneumococcus in patients with inflammatory arthritis to that in the general population, as well as to compare the chance of seroconversion across different targeted therapies. METHODS: We searched MEDLINE, Embase and the Cochrane Library databases from inception until 20 June 2023. We included randomized controlled trials and observational studies. Aggregate data were used to undertake a pairwise meta-analysis. Our primary outcome of interest was vaccine seroconversion. We accepted the definition of serological response reported by the authors of each study. RESULTS: Twenty studies were identified in the systematic review (2807 patients) with ten reporting sufficient data to be included in the meta-analysis (1443 patients). The chance of seroconversion in patients receiving targeted therapies, relative to the general population, was 0.61 (95% CI 0.35 to 1.08). The reduced odds of response were skewed strongly by the effects of abatacept and rituximab with no difference between patients on TNF inhibitors (TNFis) or IL-6 inhibition and healthy controls. Within different inflammatory arthritis populations the findings remained consistent, with rituximab having the strongest negative impact on vaccine response. TNF inhibition monotherapy was associated with a greater chance of vaccine response compared with methotrexate (2.25 (95% CI 1.28 to 3.96)). JAK inhibitor (JAKi) studies were few in number and did not present comparable vaccine response endpoints to include in the meta-analysis. The information available does not suggest any significant detrimental effects of JAKi on vaccine response. CONCLUSION: This updated meta-analysis confirms that, for most patients with inflammatory arthritis, pneumococcal vaccine can be administered with confidence and that it will achieve comparable seroconversion rates to the healthy population. Patients on rituximab were the group least likely to achieve a response and further research is needed to explore the value of multiple-course pneumococcal vaccination schedules in this population.

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.