Enabling data linkages for rare diseases in a resilient environment with the SERDIF framework.

Environmental factors amplified by climate change contribute significantly to the global burden of disease, disproportionately impacting vulnerable populations, such as individuals with rare diseases. Researchers require innovative, dynamic data linkage methods to enable the development of risk prediction models, particularly for diseases like vasculitis with unknown aetiology but potential environmental triggers. In response, we present the Semantic Environmental and Rare Disease Data Integration Framework (SERDIF).

Associations of physical activity levels with fatigue in people with inflammatory rheumatic diseases in the LIFT trial.

Objectives: The overall aim of the current study was to quantify physical activity levels in inflammatory rheumatic diseases (IRDs) and to explore their role in fatigue.

Methods: We conducted a secondary analysis of data from the Lessening the Impact of Fatigue in IRDs (LIFT) trial of the personalized exercise program (PEP) intervention for fatigue. Participants with IRDs were recruited from 2017 to 2019 and the current analysis used fatigue, measured by the Chalder Fatigue Scale (CFS) and the Fatigue Severity Scale (FSS), and accelerometer measured physical activity data collected at baseline and at the 6-month follow-up.

F-FDG-PET/MR imaging to monitor disease activity in large vessel vasculitis.

Disease-monitoring in large vessel vasculitis (LVV) is challenging. Simultaneous F-fluorodeoxyglucose positron emission tomography with magnetic resonance imaging (PET/MRI) provides functional assessment of vascular inflammation alongside high-definition structural imaging with a relatively low burden of radiation exposure. Here, we investigate the ability of PET/MRI to monitor LVV disease activity longitudinally in a prospective cohort of patients with active LVV.

Identifying key health system components associated with improved outcomes to inform the re-configuration of services for adults with rare autoimmune rheumatic diseases: a mixed-methods study.

Background: Adults with rare autoimmune rheumatic diseases face unique challenges and struggles to navigate health-care systems designed to manage common conditions. Evidence to inform an optimal service framework for their care is scarce. Using systemic vasculitis as an exemplar, we aimed to identify and explain the key service components underpinning effective care for rare diseases.

Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial.

Background: The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies.

Methods: OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies.

Brain mapping inflammatory-arthritis-related fatigue in the pursuit of novel therapeutics.

Despite developments in pharmacological treatments, chronic fatigue is an unresolved issue for most people with inflammatory arthritis that severely disrupts their personal and working lives. Fatigue in these patients is not strongly linked with peripheral disease activity but is associated with CNS-derived symptoms such as chronic pain, sleep disturbance, and depression. Therefore, a neurobiological basis should be considered when pursuing novel fatigue-specific therapeutics.

Characterizing the Neurobiological Mechanisms of Action of Exercise and Cognitive-Behavioral Interventions for Rheumatoid Arthritis Fatigue: A Magnetic Resonance Imaging Brain Study.

Objective: Chronic fatigue is a major clinical unmet need among patients with rheumatoid arthritis (RA). Current therapies are limited to nonpharmacological interventions, such as personalized exercise programs (PEPs) and cognitive-behavioral approaches (CBAs); however, most patients still continue to report severe fatigue. To inform more effective therapies, we conducted a magnetic resonance imaging (MRI) brain study of PEPs and CBAs, nested within a randomized controlled trial (RCT), to identify their neurobiological mechanisms of fatigue reduction in RA.

Immune mechanisms of depression in rheumatoid arthritis.

Depression is a common and disabling comorbidity in rheumatoid arthritis that not only decreases the likelihood of remission and treatment adherence but also increases the risk of disability and mortality in patients with rheumatoid arthritis. Compelling data that link immune mechanisms to major depressive disorder indicate possible common mechanisms that drive the pathology of the two conditions. Preclinical evidence suggests that pro-inflammatory cytokines, which are prevalent in rheumatoid arthritis, have various effects on monoaminergic neurotransmission, neurotrophic factors and measures of synaptic plasticity.

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%).

Unmet need in rheumatology: reports from the Advances in Targeted Therapies meeting, 2022.

To detail the unmet clinical and scientific needs in the field of rheumatology. After a 2-year hiatus due to the SARS-CoV-2 pandemic, the 22nd annual international Advances in Targeted Therapies meeting brought together more than 100 leading basic scientists and clinical researchers in rheumatology, immunology, epidemiology, molecular biology and other specialties. Breakout sessions were convened with experts in five rheumatological disease-specific groups including: rheumatoid arthritis (RA), psoriatic arthritis, axial spondyloarthritis, systemic lupus erythematosus and connective tissue diseases (CTDs).

Therapists' experiences of remotely delivering cognitive-behavioural or graded-exercise interventions for fatigue: a qualitative evaluation.

Objective: Fatigue is a challenging feature of all inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) included remotely delivered personalized exercise programme (PEP) or cognitive-behavioural approach (CBA) interventions. The aim of this nested qualitative evaluation was to understand rheumatology health professionals' (therapists') perspectives of delivering the interventions in the LIFT trial.

Remotely delivered cognitive-behavioural and personalized exercise interventions to lessen the impact of fatigue: a qualitative evaluation.

Objectives: Fatigue can be a disabling symptom of inflammatory rheumatic diseases. LIFT (Lessening the Impact of Fatigue in inflammatory rheumatic diseases: a randomized Trial) is a randomized trial of remotely delivered cognitive-behavioural approach or personalized exercise programme interventions, compared with usual care. The aim of this nested qualitative study was to evaluate participants' experiences of taking part in the intervention, including their ideas about future service delivery.

Brain predictors of fatigue in rheumatoid arthritis: A machine learning study.

Background: Fatigue is a common and burdensome symptom in Rheumatoid Arthritis (RA), yet is poorly understood. Currently, clinicians rely solely on fatigue questionnaires, which are inherently subjective measures. For the effective development of future therapies and stratification, it is of vital importance to identify biomarkers of fatigue.

The association between ambient UVB dose and ANCA-associated vasculitis relapse and onset.

Background: The aetiology of ANCA-associated vasculitis (AAV) and triggers of relapse are poorly understood. Vitamin D (vitD) is an important immunomodulator, potentially responsible for the observed latitudinal differences between granulomatous and non-granulomatous AAV phenotypes. A narrow ultraviolet B spectrum induces vitD synthesis (vitD-UVB) via the skin.

Large-vessel vasculitis.

Large-vessel vasculitis (LVV) manifests as inflammation of the aorta and its major branches and is the most common primary vasculitis in adults. LVV comprises two distinct conditions, giant cell arteritis and Takayasu arteritis, although the phenotypic spectrum of primary LVV is complex. Non-specific symptoms often predominate and so patients with LVV present to a range of health-care providers and settings.