Systemic Lupus Erythematosus (SLE) is a multi-system autoimmune disorder, characterised by activation of the interferon system. Of the multiple domains of this disease, patients identify fatigue as the most pervasive and disabling aspect. As many as 90% report significant levels of fatigue, a prevalence far in excess of that observed in the general population and most other chronic disorders. Moreover, its impact permeates all aspects of living as reflected by fatigue's strong relationship with impaired quality of life3 and work disability. Despite these substantial consequences, relatively little is known about this symptom and so the current dearth of accepted therapies is unsurprising. A better understanding of the underlying mechanisms of fatigue will be vital if efficacious interventions are to be developed in the future.
The investigators will recruit 25 SLE patients to achieve 20 full data sets. They will attend for a baseline 7T brain scan to primarily measure basal ganglia glutamate and then receive 5 months of a pharmacological blocker that antagonises type 1 interferon receptors before completing the study with a final 7T brain scan to undertake repeat measure of basal ganglia glutamate.
Adults ≥ 18 years < 65 years
Fulfilment of the 2019 ACR (American College of Rheumatology)/EULAR (European Alliance of Associations for Rheumatology) classification criteria for SLE
Persistent (>3 months) and clinically significant fatigue (≥6 on numerical rating 0-10 scale measuring average level of fatigue during the past 7 days)
Attainment of Lupus low disease activity state (LLDAS)
Inability to provide informed written consent
Moderate or severe active SLE
Severe active CNS (Central Nervous System) Lupus and Lupus Nephritis
Contra-indications to anifrolumab
SLE Patients attending NHS Greater Glasgow \& Clyde, NHS Lanarkshire, NHS Forth Valley, NHS Tayside and NHS Grampian rheumatology department with low disease activity state aged over 18 years less than75 years. The total number of participants will be 20.
Cohort
Prospective
Anifrolumab
DrugAnifrolumab 300mg intravenous infusions administered as described in the EU SmPC
Changes in basal ganglia glutamate levels
Changes in basal ganglia glutamate levels measured by 7T MRI following pharmacological blockade of type 1 interferon receptors in SLE .
Changes in dorsal attention network (DAN)
Changes in dorsal attention network (DAN) as measured by 7T MRI
Changes in default mode network (DMN) - insula brain connectivity
Changes in default mode network (DMN) - insula brain connectivity as measured by 7T MRI
Changes of fatigue as measured via Functional Assessment of Chronic Illness Therapy - Fatigue Scale
To describe any changes of fatigue in association with altered glutamate and brain functional connectivity using the Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-F). The FACIT-F scale consists of 13 items that assess the level of fatigue experienced by the respondent over the past 7 days. These items cover various aspects of fatigue, such as physical, emotional, and functional well-being. Each item is rated on a 5-point Likert scale, with response options ranging from "Not at all" (0) to "Very much" (4). The respondent selects the option that best describes their experience. The scores for each item are summed to create a total score. Some items are reverse-scored to ensure that higher scores consistently indicate better functioning and less fatigue. The total score can range from 0 to 52, with higher scores indicating less fatigue and better quality of life.
Changes of fatigue as measured via the Patient-Reported Outcomes Measurement Information System Fatigue Scale.
To describe any changes of fatigue in association with altered glutamate and brain functional connectivity using the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale. The PROMIS Fatigue Scale includes a large item bank with questions related to fatigue. These questions cover various aspects of fatigue, such as its intensity, frequency, and impact on daily activities. Each question has five response options, usually ranging from "Not at all" to "Very much." These responses are scored on a scale from 1 to 5, with higher scores indicating greater fatigue.
Longitudinal modulation of the Type 1 Interferon Transcriptomic Signature in the Peripheral Immune Compartment
This outcome investigates the changes in the pattern of gene expression related to type 1 interferons over time in the immune cells found in the blood and other peripheral tissues. These changes will be measured as part of research blood samples in each visit.
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