Trust performance in managing inflammatory arthritis over time in England and Wales: a latent class analysis approach.

Objectives: To evaluate trust-level performance in time to initiation of DMARD therapy in patients with early inflammatory arthritis (EIA), with identification of the change in performance trajectories over time and investigation of trust characteristics associated with this change. Methods: We included 130 trusts from the UK contributing to the National Early Inflammatory Arthritis Audit (NEIAA) from 2018 to 2020. The primary outcome was days from referral to initiation of DMARD therapy in patients with EIA. Latent class growth mixture models were applied to identify distinct groups of trusts with similar trajectories of performance change over time. We used mixed effects linear and multinomial logistic regression models to evaluate the association between delay in treatment and trust-level characteristics. Results: The mean time to DMARD initiation was 53 days (s.d. 18), with an average 0.3-day decrease with each month over time. Four latent trajectories were identified in our cohort, with >77% of individual trusts showing ongoing improvements in decreasing treatment waiting times. Prior to separating by latent class, time to DMARD initiation was shorter in trusts with higher rheumatology staffing, a local EIA treatment pathway and those with access to musculoskeletal ultrasound. Trusts with more nurses in the rheumatology department were less likely to be in the worst performance group [odds ratio 0.69 (95% CI 0.49, 0.93)]. Conclusion: In this cohort study, we observed a reduction in treatment waiting time over time. Trusts with better staffed and improved EIA clinical structure are likely to initiate definitive treatment earlier in patients with EIA.

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.

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.

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.

Patient-Initiated Follow-Up.

In the contemporary healthcare climate, we are acutely aware that our resources are finite. This is particularly pertinent in government-funded healthcare settings, where clinical teams often face the challenge of meeting increasing patient demand with static or dwindling capacity.1-4.

Understanding the psychosocial determinants of effective disease management in rheumatoid arthritis to prevent persistently active disease: a qualitative study.

BACKGROUND: According to epidemiological studies, psychosocial factors are known to be associated with disease activity, physical activity, pain, functioning, treatment help-seeking, treatment waiting times and mortality in people with rheumatoid arthritis (RA). Limited qualitative inquiry into the psychosocial factors that add to RA disease burden and potential synergistic interactions with biological parameters makes it difficult to understand patients' perspectives from the existing literature. AIM: This study aimed to gather in-depth patient perspectives on psychosocial determinants that drive persistently active disease in RA, to help guide optimal patient care. METHODS: Patient research partners collaborated on the research design and materials. Semistructured interviews and focus groups were conducted online (in 2021) with patients purposively sampled from diverse ethnicities, primary languages, employment status and occupations. Data were analysed using inductive thematic analysis. RESULTS: 45 patients participated across 28 semistructured interviews and three focus groups. Six main themes on psychosocial determinants that may impact RA management were identified: (1) healthcare systems experiences, (2) patient education and health literacy, (3) employment and working conditions, (4) social and familial support, (5) socioeconomic (dis)advantages, and (6) life experiences and well-being practices. CONCLUSION: This study emphasises the importance of clinicians working closely with patients and taking a holistic approach to care that incorporates psychosocial factors into assessments, treatment plans and resources. There is an unmet need to understand the relationships between interconnected biopsychosocial factors, and how these may impact on RA management.

Pain sensitisation and joint inflammation in patients with active rheumatoid arthritis.

INTRODUCTION: Despite better therapies and strategies, many people with rheumatoid arthritis (RA) have persistent pain, often from abnormal pain processing, now termed nociplastic pain. However, RA patients with fibromyalgia (FM), a central nociplastic pain syndrome, also have power doppler ultrasound (PDUS+) joint inflammation. To understand the complex causes of pain, we performed clinical examination and patient-reported outcome measures (PROMs) plus comprehensive PDUS evaluation not previously combined. METHODS: In a cross-sectional study of sequential RA patients with at least moderate DAS28 erythrocyte sedimentation rate disease activity, we assessed 66/68 joints for swelling and tenderness, respectively, FM American College of Rheumatology 2010 diagnostic criteria, completed PROMs for function, quality of life and mood, alongside PDUS examination of 44 joints. Statistical analysis included logistic regression modelling and regularised (lasso) logistic regression methods. RESULTS: From 158 patients, 72 (46%) patients met FM criteria, with significantly worse tender joint counts and PROMs, but no differences in PDUS compared with the non-FM group. Categorising patients by PDUS+ joint presence and/or FM criteria, we identified four distinct groups: 43 (27.2%) patients with -FM-PD, 43 (27.2%) with -FM+PD, 42 (26.6%) with +FM-PD and 30 (19%) with +FM+PD. Both FM+ groups had worse PROMs for fatigue, mood and pain, compared with the FM- groups. We were unable to develop algorithms to identify different groups. CONCLUSION: The unexpected group -FM-PD group may have peripheral nociplastic pain, not commonly recognised in rheumatology. Only 46% of patients demonstrated PDUS+ inflammation. However clinical examination and PROMs did not reliably differentiate groups, emphasising PDUS remains an important tool.

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.

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.

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.

Efficacy and safety of JAK inhibitors in rheumatoid arthritis: update for the practising clinician.

Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, upadacitinib and filgotinib, are increasingly used in the treatment of rheumatoid arthritis (RA). There has been debate about their safety, particularly following the issuance of guidance by regulatory agencies advising caution in their use in certain patients. The registrational clinical trials and registry data of JAK inhibitors did not identify a difference in the risk of major adverse cardiovascular events (MACEs), venous thromboembolism, malignancies or infections (other than herpes zoster) with a JAK inhibitor versus a biologic DMARD. In the ORAL Surveillance trial, which enrolled patients >50 years of age with ≥1 cardiovascular risk factor, tofacitinib was statistically inferior to TNF inhibitors for the occurrence of MACEs and malignancy. Further post hoc analysis of the data revealed that an age of ≥65 years, a high baseline cardiovascular risk, a history of smoking, sustained inflammation, disease activity and suboptimal treatment of cardiovascular comorbidities all increase the risk of these outcomes. The guidance issued by regulatory agencies should be carefully considered to ensure appropriate and safe treatment of patients with RA without undertreatment of patients who might benefit from JAK inhibitor, as well as biologic, treatment. As always, the risks associated with the use of these agents, treatment goals, costs and patient preferences should be discussed with the patient.

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.

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.

Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis.

OBJECTIVE: Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA. METHODS: We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool. RESULTS: Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo. CONCLUSION: Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.