PEPSeek-mediated identification of novel epitopes from viral and bacterial pathogens and the impact on host cell immunopeptidomes.

Here, we develop PEPSeek, a web-server based software to allow higher performance in the identification of pathogen-derived epitope candidates detected via mass spectrometry in MHC class I immunopeptidomes. We apply it to human and mouse cell lines infected with either SARS-CoV-2, Listeria monocytogenes or Chlamydia trachomatis, thereby identifying a large number of novel antigens and epitopes that we prove to be recognized by CD8 T cells. In infected cells, we identified antigenic peptide features that suggested how processing and presentation of pathogenic antigens differ between pathogens.

Abatacept and the risk of malignancy: a meta-analysis across disease indications.

Objectives: To estimate the association between abatacept use and the incidence of malignancy excluding non-melanomatous skin cancers (NMSCs).

Methods: Systematic database searches were performed, to April 2024, to identify phase II/III/IV randomised clinical trials (RCTs), long-term extension (LTE) and observational cohort studies of abatacept in people with rheumatoid arthritis and psoriatic arthritis. Network and pairwise meta-analyses were performed to estimate incidence rate ratios (IRRs) for malignancy excluding NMSC, comparing abatacept with placebo and tumour necrosis factor inhibitors (TNFi) in RCT/LTE studies.

Therapeutic interception in individuals at risk of rheumatoid arthritis to prevent clinically impactful disease.

Multiple clinical trials for rheumatoid arthritis (RA) prevention have been completed. Here, we set out to report on the lessons learnt from these studies. Researchers who conducted RA prevention trials shared the background, rationale, approach and outcomes and evaluated the lessons learnt to inform the next generation of RA prevention trials.

Self-management behaviors do not affect remission but mediate between mental health and disease outcomes in a longitudinal study of rheumatoid arthritis.

Mental health has been shown to impact rheumatoid arthritis (RA) outcomes and is associated with self-management behaviors. The extent to which mental health impacts outcomes via different self-management behaviours has not been thoroughly investigated. Adult RA patients who were starting a new medication or dosage were recruited to a prospective cohort with follow-ups at 3 and 12-months covering clinical and patient-reported outcomes.

Temporal and regional variation in the use of biologic and targeted synthetic DMARDs for rheumatoid arthritis: a nationwide cohort study.

Objective: To evaluate temporal and regional variation in biologic and targeted synthetic DMARD (b/tsDMARD) initiation for rheumatoid arthritis (RA) in England and Wales.

Methods: An observational cohort study was conducted for people with RA enrolled in the National Early Inflammatory Arthritis Audit (NEIAA) between May 2018 and April 2022 who had 12-month follow-up data. Temporal trends in escalation to b/tsDMARDs within 12 months of initial rheumatology assessment were explored, including comparisons before and after publication (July 2021) of national guidelines that lowered the threshold for b/tsDMARD initiation to include moderate-severity RA.

NK cell subsets define sustained remission in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an immune-mediated, chronic inflammatory condition. With modern therapeutics and evidence-based management strategies, achieving sustained remission is increasingly common. To prevent complications associated with prolonged use of immunosuppressants, drug tapering or withdrawal is recommended.

What role do socioeconomic and clinical factors play in disease activity states in rheumatoid arthritis? Data from a large UK early inflammatory arthritis audit.

Background: Persistently active rheumatoid arthritis (pactiveRA) may be due to the interplay between biological and non-biological factors. The role of socioeconomic factors remains unclear.

Objectives: To explore which biological and non-biological factors associate with pactiveRA.

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.

Longitudinal effects of affective distress on disease outcomes in rheumatoid arthritis: a meta-analysis and systematic review.

Patients with rheumatoid arthritis have higher rates of mental health conditions compared to the general population. It is believed that affective distress and rheumatoid arthritis have a bi-directional relationship. This review will examine the associations between affective distress and rheumatoid arthritis outcomes over time.

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.

Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial.

Background: Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept.

Methods: The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands.

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.

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

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. 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).

Mental health, quality of life and self-management behaviours: online evaluation of inflammatory arthritis patients over 1 year of COVID-19 lockdowns.

Objective: Patients with inflammatory arthritis were especially vulnerable to the psychosocial and health impacts of coronavirus disease 2019 (COVID-19) and the lockdowns. This study investigated the impact of these changes on mental health, physical health and quality of life for inflammatory arthritis patients over 1 year following the initial lockdown in the UK.

Methods: Three hundred and thirty-eight participants with inflammatory arthritis completed an ambidirectional study consisting of online questionnaires at four time points for 1 year.

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.

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial.

Background: From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19.

Methods: TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score.

Implementing treat-to-target urate-lowering therapy during hospitalizations for gout flares.

Objectives: To evaluate a strategy designed to optimize care and increase uptake of urate-lowering therapy (ULT) during hospitalizations 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-hospitalization rates, were compared between patients hospitalized for flares in the 12 months post-implementation and a retrospective cohort of hospitalized patients from 12 months pre-implementation.

Extracellular matrix rigidity modulates physical properties of subcapsular sinus macrophage-B cell immune synapses.

Subcapsular sinus macrophages (SSMs) play a key role in immune defense by forming immunological barriers that control the transport of antigens from lymph into lymph node follicles. SSMs participate in antibody responses by presenting antigens directly to naive B cells and by supplying antigens to follicular dendritic cells to propagate germinal center reactions. Despite the prominent roles that SSMs play during immune responses, little is known about their cell biology because they are technically challenging to isolate and study in vitro.

Rheumatoid arthritis prevention in arthralgia: fantasy or reality?

The concept of a 'window of opportunity' in treating a disease assumes the existence of a time frame during which the trajectory of the disease can be effectively and permanently modified. In rheumatoid arthritis (RA), optimal timing of this period is presumed to be during the phase before arthritis is clinically apparent and disease is diagnosed. Several proof-of-concept trials of treatment during the 'arthralgia' phase of RA have been completed in the past 4 years, with the underlying notion that temporary treatment at this stage could prevent the development of RA or induce a sustained reduction in the burden of disease.

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.

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.

Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.

Background: The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit.