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.

The incidence and prevalence of Juvenile Idiopathic Arthritis differs between ethnic groups in England.

OBJECTIVES: Juvenile Idiopathic Arthritis (JIA) is a heterogenous group of rare autoimmune disorders characterised by chronic joint inflammation of unknown aetiology with onset under 16years. Accurate estimates of disease rates help understand impacts on individuals and society, and provide evidence for health service planning and delivery. This study aimed to produce the first national estimates of incidence and prevalence by ethnic group using electronic health records. METHODS: Data from the Clinical Practice Research Datalink (CPRD) Aurum, a primary care electronic health record database in England, were used to estimate the incidence and prevalence of JIA by ethnic group amongst children and young people aged under 16 years between 2003 and 2018, with cases validated using Hospital Episode Statistics (HES). Chi square was used to test the difference in proportions compared to the ethnic distribution of England. RESULTS: A total of 424 incident cases of JIA were identified, 389 validated using HES records. Incidence of JIA was higher amongst those of White ethnic group (6.2 per 100,000 population) compared to Mixed (3.0 per 100,000), Asian (2.7 per 100,000) and Black (2.9 per 100,000) communities. The ethnic group distribution of cases differed significantly compared to the general population (p < 0.0001). CONCLUSION: Incidence and prevalence of JIA differs between ethnic groups, and is different from the population. This is likely to be due to a combination of genetic and equity factors. Further research to understand the underlying cause of these differences is important, to enable targeted interventions and appropriate service provision.

Using Polygenic Risk Scores to Aid Diagnosis of Patients With Early Inflammatory Arthritis: Results From the Norfolk Arthritis Register.

OBJECTIVE: There is growing evidence that genetic data are of benefit in the rheumatology outpatient setting by aiding early diagnosis. A genetic probability tool (G-PROB) has been developed to aid diagnosis has not yet been tested in a real-world setting. Our aim was to assess whether G-PROB could aid diagnosis in the rheumatology outpatient setting using data from the Norfolk Arthritis Register (NOAR), a prospective observational cohort of patients presenting with early inflammatory arthritis. METHODS: Genotypes and clinician diagnoses were obtained from patients from NOAR. Six G-probabilities (0%-100%) were created for each patient based on known disease-associated odds ratios of published genetic risk variants, each corresponding to one disease of rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, spondyloarthropathy, gout, or "other diseases." Performance of the G-probabilities compared with clinician diagnosis was assessed. RESULTS: We tested G-PROB on 1,047 patients. Calibration of G-probabilities with clinician diagnosis was high, with regression coefficients of 1.047, where 1.00 is ideal. G-probabilities discriminated clinician diagnosis with pooled areas under the curve (95% confidence interval) of 0.85 (0.84-0.86). G-probabilities <5% corresponded to a negative predictive value of 96.0%, for which it was possible to suggest >2 unlikely diseases for 94% of patients and >3 for 53.7% of patients. G-probabilities >50% corresponded to a positive predictive value of 70.4%. In 55.7% of patients, the disease with the highest G-probability corresponded to clinician diagnosis. CONCLUSION: G-PROB converts complex genetic information into meaningful and interpretable conditional probabilities, which may be especially helpful at eliminating unlikely diagnoses in the rheumatology outpatient setting.

Continuing specialist care into adulthood in young people with juvenile idiopathic arthritis: a retrospective cohort study using electronic health records in England.

OBJECTIVES: This study aimed to measure (1) the proportion of children who continue to receive specialist care (rheumatology/ophthalmology) as adults, (2) the characteristics associated with continuing specialist care, and (3) the frequency of specialist care appointments in both paediatric and adult services. METHODS: A retrospective cohort of young people with JIA was identified from UK primary care electronic health records (Clinical Practice Research Datalink) between 1 April 2003 and 31 December 2018. To be included in the study, cases needed to have at least 1 year of registration at their general practice beyond age 18 and linkage to Hospital Episodes Statistics data for secondary care information. All specialist care outpatient visits were identified from Hospital Episodes Statistics outpatient data. RESULTS: There were 666 young people included in the study. Of these, 427 (64%) received specialist care beyond age 18, 90 (13%) had their last recorded contact at 16-17 years and 149 (22%) did not continue after 16 years. Older age at diagnosis, female gender, less deprivation and a childhood diagnosis of uveitis were associated with continuing specialist care beyond age 18. Of those continuing beyond 18, 35% (n = 153) were subsequently discharged by the study end date. Of all those discharged, 32% had a missed appointment recorded after the last attended visit, suggesting failure to attend. CONCLUSIONS: Two-thirds of young people with JIA continue to receive specialist care beyond age 18. This is useful information for children and young people with JIA and their families planning for their future, and for clinicians planning health-care services.

Incidence and prevalence of juvenile idiopathic arthritis in the United Kingdom, 2000-2018: results from the Clinical Practice Research Datalink.

OBJECTIVE: The incidence and prevalence of JIA was last estimated in the UK in 1994. Since then the disease has been reclassified, the specialty of paediatric rheumatology has evolved and there has been a significant shift in disease management with new advanced therapies. This study aimed to provide up-to-date national estimates of this disease. METHODS: Children and young people (CYP) with JIA were identified in the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases, which source data from the two most commonly used primary care electronic health record systems in the UK. These databases were combined and the cohort was identified (2000-18) using predefined code lists. Validation was performed through linkage to the England Hospital Episode Statistics. Annual incidence and prevalence rates were calculated and stratified by gender, age group and nation of the UK. Direct standardization to the UK population was performed and 5 year incidence rates were calculated between 2003 and 2018. RESULTS: The age-standardized incidence rate was 5.61 per 100 000 population. The age-standardized prevalence rate in 2018 was 43.5 per 100 000. Rates were higher in Scotland compared with England: incidence rate ratio 1.27 (95% CI 1.11, 1.46). The 5 year incidence rates did not change significantly over time. CONCLUSIONS: This study has provided the first contemporaneous estimates of occurrence of JIA in the UK in 25 years. These data provide important estimates to inform resource allocation and health service development for management of JIA.

The impact of lifestyle behaviours, physical activity and smoking on morbidity and mortality in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with pain, disability and increased risk of developing comorbidities and premature mortality. While these poor outcomes have improved in line with advances in the treatment of RA, they still persist to some degree today. Physical activity and smoking are two areas of patients' lives where changes may have a substantial impact on the poor outcomes associated with RA. Physical activity in RA has been well studied, with many randomised trials indicating the benefits of physical activity on pain and disability. A number of observational studies have assessed the impact of smoking on RA, also indicating the benefits of quitting smoking on RA-related outcomes, but with less consistent findings, potentially due to epidemiological challenges (e.g. collider bias, recall bias). There are also a number of barriers preventing patients making these positive lifestyle changes, such as lack of time and motivation, lack of knowledge and advice, as well as disease-specific barriers, such as pain and fatigue.

The effect of glucocorticoid therapy on mortality in patients with rheumatoid arthritis and concomitant type II diabetes: a retrospective cohort study.

BACKGROUND: Patients with rheumatoid arthritis (RA) have increased cardiovascular (CV) and mortality risk. Patients with RA are also frequently prescribed glucocorticoids (GCs) which have been associated with increased risk of mortality. In addition, for patients who have concomitant diabetes mellitus (DM), GCs are known to worsen glycaemic control and hence may further increase CV and mortality risk. This study aimed to understand the relationship between GCs, DM and mortality in patients with RA. METHODS: This was a retrospective cohort study of patients with incident RA identified from UK primary care electronic medical records. Patients with linkage to Office for National Statistics (ONS) for mortality data (N = 9085) were included. DM was identified through Read codes, prescriptions and blood tests, and GC use was identified through prescriptions. Mortality rate ratios (RR) and rate differences (RD) were calculated across the different exposure groups. Cox proportional hazards regression models were used to estimate interaction on the multiplicative and additive scales. RESULTS: In those without DM GC use had a 4.4-fold increased all-cause mortality RR (95% confidence interval (CI): 3.83 to 5.14) compared to non-use, whilst those with DM had a lower RR for GC use (3.02 (95% CI: 2.34, 3.90)). However, those with DM had a higher RD associated with GC use because of their higher baseline risk. In those with DM, GC use was associated with an additional 46.7 deaths/1000 person-years (pyrs) (95% CI: 34.1 to 59.3) compared to non-use, while in those without DM GC use was associated with an additional 36.2 deaths/1000 pyrs (95% CI: 31.6 to 40.8). A similar pattern was seen for CV mortality. The adjusted Cox proportional hazards model showed no evidence of multiplicative interaction, but additive interaction indicated a non-significant increased risk. For CV mortality there was no interaction on either scale. CONCLUSIONS: GC use was associated with higher mortality rates in people with comorbid DM compared to people without DM, despite apparently reassuring similar relative risks. Clinicians need to be aware of the higher baseline risk in patients with DM, and consider this when prescribing GCs in patients with RA and comorbid DM.

Quantifying the hepatotoxic risk of alcohol consumption in patients with rheumatoid arthritis taking methotrexate.

BACKGROUND: Patients with rheumatoid arthritis (RA) who take methotrexate (MTX) are advised to limit their alcohol intake due to potential combined hepatotoxicity. However, data are limited to support this. The aim of this study was to quantify the risk of developing abnormal liver blood tests at different levels of alcohol consumption, using routinely collected data from primary care. METHODS: Patients with RA in the Clinical Practice Research Datalink starting MTX between 1987 and 2016 were included. Hepatotoxicity was defined as transaminitis: alanine transaminase or aspartate aminotransferase more than three times the upper limit of normal. Crude rates of transaminitis were calculated per 1000 person-years, categorised by weekly alcohol consumption in units. Cox proportional hazard models tested the association between alcohol consumption and transaminitis univariately, then age and gender adjusted. RESULTS: 11 839 patients were included, with 530 episodes of transaminitis occurring in 47 090 person-years follow-up. Increased weekly alcohol consumption as a continuous variable was associated with increased risk of transaminitis, adjusted HR (95% CI) per unit consumed 1.01 (1.00 to 1.02); consuming between 15 and 21 units was associated with a possible increased risk of hepatotoxicity, while drinking >21 units per week significantly increased rates of transaminitis, adjusted HR (95% CI) 1.85 (1.17 to 2.93). CONCLUSIONS: Weekly alcohol consumption of <14 units per week does not appear to be associated with an increased risk of transaminitis.