Effect of Anifrolumab on Arterial Inflammation in Systemic Lupus Erythematosus Study (AISLE)

Inclusion Criteria:

1. Male or female participants 18 to 70 years of age
2. Able to give written, informed consent and to lie flat for scanning
3. Fulfil American College of Rheumatology/European Alliance of Associations for Rheumatology 2019 classification criteria for SLE
4. Current antinuclear antibody positive (ANA-ELISA ≥1.0, ANA Hep2 positivity)
5. Have ≥4 points on the clinical SLEDAI-2K disease activity score
6. Stable standard of care SLE therapies for ≥4 weeks
7. Prednisolone dosage ≤7.5 mg (or equivalent) daily
8. Up to date on required vaccinations (e.g., pneumonia, varicella zoster, and influenza [inactivated/recombinant]) prior to study entry

Exclusion Criteria:

1. Women of child-bearing potential not using adequate contraception
2. Breastfeeding
3. Already taking anifrolumab
4. Allergy and/or contraindication to anifrolumab or excipients
5. Anaphylaxis to any human gamma globulin therapy
6. History of recurrent infections requiring hospitalisation and intravenous (IV) antibiotics (e.g., 3 or more of the same type of infection over the previous 52 weeks)
7. Active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection, confirmed by (a) HBsAg; or (b) HBcAb and HBV DNA detected above the lower limit of quantitation by reflex testing; or (c) HCV RNA
8. Any severe case of herpes zoster (HZ) infection, including, but not limited to: (a) systemic HZ such as herpes encephalitis or ophthalmic herpes involving the retina at any time prior to signing the ICF; (b) recurrent cutaneous HZ defined as 2 or more episodes within 2 years prior to signing the ICF; (c) any HZ infection that has not completely resolved within 12 weeks prior to signing the ICF
9. Any active cytomegalovirus or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF.
10. Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years prior to signing the ICF
11. Any of the following infections: (a) clinically significant chronic infection (i.e., osteomyelitis, bronchiectasis, etc) within 8 weeks prior to signing the ICF (chronic nail infections are allowed); (b) any infection requiring hospitalization or treatment with IV anti-infectives not completed at least 4 weeks prior to signing the ICF; (c) any infection requiring oral anti-infectives (including antivirals) within 2 weeks prior to signing the ICF
12. Any live or attenuated vaccine within 8 weeks prior to signing the informed consent form (ICF). Administration of killed or subunit vaccines is acceptable
13. Immunocompromised (known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for human immunodeficiency virus)
14. History of active tuberculosis or latent tuberculosis in whom an adequate course of treatment could not be confirmed
15. History of cancer (other than squamous or basal cell carcinoma of the skin/cervical cancer in situ treated with curative therapy more than 3 months prior to signing the ICF)
16. Receiving other biological therapies or monoclonal antibodies
17. Received rituximab or obinutuzumab within the past 24 weeks
18. Received belimumab within the past 12 weeks

18. Received cyclophosphamide in the past 6 months 19. Cardiovascular event ≤3 months 20. Contra-indication to MRI or CT scanning 21. Contrast allergy or contrast-nephropathy 22. Active nephritis (>1g protein/24hr or albumin to creatine ratio >100) 23. Active central nervous system lupus 24. Active myocarditis 25. Chronic kidney disease (eGFR <30 mL/min/1.73 m2) 26. Any condition that, in the opinion of the Investigator, would with impact patient safety, ability to complete imaging, or interfere with the interpretation of the study findings