Anifrolumab for Systemic Lupus Erythematosus and Vascular Risk

* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Male or female, aged 18-80 years 4. In good general health as evidenced by medical history or diagnosed with SLE diagnosed per American College of Rheumatology 1997 revised SLE classification criteria. 5. Prednisone \< or equal to 10 mg/day for at least 2 weeks before screening and maintained throughout randomization (day 1) 6. Stable standard of care lupus therapies for at least 4 weeks before screening and maintained through randomization (day 1) 7. Abnormal cardio-ankle vascular index (CAVI) (based on 2 SD above median of healthy controls based on historical data from our own patient cohorts AND/OR 8. Abnormal Pulse wave velocity (PWV) using Sphygmocor. AND/OR 9. Abnormal target to background ratio (TBR) in various aortic territories and total aorta using FDG PET CT scan. 10. Stable medications for diabetes, hypertension and/or statins for at least the previous 3 months. Adjustments to diabetic medications may be allowed as per the discretion of PI. No changes of any other medications or immunosuppressive drugs will be allowed during trial. The PI will consult with DMSC members if changes to diabetic medications are being considered and the change will be documented. 11. For females and males of reproductive potential: use of highly effective contraception from screening and agreement to use such a method during study participation and for an additional 16 weeks after the end of study medication administration. For the purpose of this study abstinence will be considered as an effective form of contraception. 12. Subjects must confirm receipt of prior vaccination against COVID-19 and Varicella Zoster. Verbal confirmation of vaccination receipt AND detectable antibodies in serum is acceptable in the absence of vaccine records. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: * Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results. * Concurrent enrolment in another clinical study with an investigational product * Major surgery within 8 weeks before signing the ICF or elective major surgery planned during the study period. * Any of the following found at Screening: * Aspartate aminotransferase (AST) \>2.5 x upper limit of normal (ULN). * Alanine aminotransferase (ALT) \>2.0 x ULN. * Total bilirubin \>ULN (unless due to Gilbert's syndrome) * Serum creatinine \>2.5 mg/dL (or \>181 micromol/L) * Urine protein/creatinine ratio \>2.0 mg/mg (or \>226.30 mg/mmol) * Neutrophil count \<1000/microL (or \<1.0 x 109/L) * Platelet count \<25000/microL (or \<25 x 109/L) * Hemoglobin \<8 g/dL (or \<80 g/L), or \<7 g/dL (or \<70 g/L) if related to subject's SLE such as in active hemolytic anemia * Glycosylated hemoglobin (HbA1c) \>8% (or \>0.08) at screening (diabetic subjects only). Patients with HbA1c \>8% may be eligible for study if considered to be at low risk of infection and vascular complications at the discretion of study PI. * Positive SARS/Flu A/B/RSV (Panther), PCR - risk-based testing, only required if patient is symptomatic or has been exposed to someone with the virus. Note: Abnormal screening test(s) which exclude the patient may be repeated once within 4 weeks of the Screening Visit. If the repeat test(s) does not meet the above criteria, then the patient may be included in the study and will not be considered a screen failure. * Receipt of any of the following: 1. Azathioprine \>200 mg/day 2. Mycophenolate mofetil \> 3 g/day or mycophenolic acid \>2.16 g/day 3. Oral, SC, or intramuscular methotrexate \>25 mg/week 4. Mizoribine \>150 mg/day. Leflunomide more than 20 mg and any other immunosuppressant usage at the discretion of the PI. * Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to week 0 (day 1), whichever is greater. * Receipt of any commercially available biologic agent within 5 half-lives prior to signing of the ICF * Receipt of B cell depleting therapy (including but not limited to belimumab, ocrelizumab, ofatumumab, atacicept, Obinutuzumab, or rituximab), \<26 weeks prior to the signing of the consent for all B-cell depleting therapy or \<40 weeks prior to the signing of the ICF for atacicept. * Receipt of any of the following: (a) Intra-articular, intramuscular or IV corticosteroids within 4 weeks prior to Day 1 (b) Any live or attenuated vaccine within 8 weeks prior to signing the ICF (administration of killed vaccines is acceptable) * History or evidence of suicidal ideation within the past 6 months; or any suicidal behavior within the past 12 months based on screening or at baseline. * Recent cardiac or stroke event (with in the last year prior to week 0 (day 1)) * Active SLE disease with SLEDAI 2K \>6 at the time of screening. * Active severe or unstable neuropsychiatric SLE including, but not limited to: aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; and mononeuritis multiplex: 1. That would make the subject unable to fully understand the ICF OR 2. Where, in the opinion of the Principal Investigator (PI), protocol specified SOC is insufficient and utilization of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated * Active severe SLE-driven renal disease where, in the opinion of the PI, protocol specified standard of care (SOC) is insufficient and utilization of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated. * History of or current diagnosis of catastrophic or severe anti-phospholipid syndrome within 1 year prior to signing the ICF. Antiphospholipid syndrome adequately controlled by anticoagulant therapy for at least 3 months is acceptable. * Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation. * Confirmed positive test for hepatitis B serology for: 1. Hepatitis B surface antigen (HBsAg), OR 2. Hepatitis B core antibody (HBcAb) 3. If positive for HBcAb, hepatitis B virus (HBV) DNA will be checked. If HBV DNA is detected above the lower limit of quantitation (LLOQ) at screening subject will be excluded Note: Subjects who are only HBcAb positive at screening will be tested every month for HBV DNA. To remain eligible for the study, the subject s HBV DNA levels must remain below the LLOQ as per the central laboratory. * Positive test for hepatitis C antibody along with detectable Hepatitis C viral RNA. * Any severe herpes infection at any time prior to Week 0 (Day 1), including, but not limited to, disseminated herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years) or ophthalmic herpes (ever) * Any herpes zoster, cytomegalovirus (CMV) or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF. * Any of the following: 1. Clinically significant chronic infection (i.e., osteomyelitis, bronchiectasis, etc.) within 8 weeks prior to week 0 (day1) (chronic nail infections are allowed) 2. Any infection requiring hospitalization or treatment with IV antibiotics not completed at least 4 weeks prior to week 0 (day1) * Any infection requiring oral antimicrobials (including antivirals) within 2 weeks prior to Day 1, except if taking antivirals/antimicrobials prophylactically. * History of cancer, apart from: 1. Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy \>=3 months prior to Week 0 (Day 1) 2. Cervical cancer in situ treated with apparent success with curative therapy \>=1 year prior to Week 0 (Day 1). * Pregnancy or lactation or intend to become pregnant anytime from initiation of Screening until completion of study. * Spontaneous or induced abortion, still or live birth, or pregnancy \<= 4 weeks prior to week 0 (day1) * Known allergic reactions to any component of the investigational product formulation or history of anaphylaxis to any human gamma globulin therapy. * Tested positive for COVID-19 infection on the day of screening or up to 21 days prior to screening.