Table 1 Entry criteria. In- and exclusion criteria of the Synbiose 2 study

• ≥ 18 years of age

• Having a clinical diagnosis of SLE according to the SLICC criteria 2012

• Severe, active SLE defined as one or more of the following:

◦ SLEDAI ≥ 12

◦ New or worse SLE-related activity in major organs, i.e., CNS-SLE (includes NPSLE), vasculitis, nephritis, pericarditis and/or myocarditis, myositis, thrombocytopenia (< 60 × 10⁹/L), hemolytic anemia (Hgb < 4.4mmol/L = 7.0 g/dL)

◦ High disease activity that requires or warrants induction treatment by switching to or increasing dosage of oral mycophenolate

• New, persisting or progressive disease activity despite the use of conventional maintenance immunosuppressive treatment (e.g., mycophenolate or azathioprine)

• Confirmed positive SLE-specific autoantibodies defined as one or more of the following:

◦ ANA titer ≥ 1:80

◦ Either 2 positive test results from independent time points within the study screening period, or one positive historical test result and 1 positive result during the screening period

◦ Anti-dsDNA serum antibody ≥ 30 IU/mL

◦ Either 2 positive test results from independent time points within the study screening period, or one positive historical test result and 1 positive result during the screening period

• Female patients who arepregnant or breastfeeding

• Significant hypogammaglobulinemia (IgG < 4.0 g/L) or IgA deficiency (IgA < 0.1 g/L)

• Immunization with a live vaccine within 1 month preceding day 0

• Active infection, defined as one or more of the following:

◦ Hospitalization for treatment of infection within 60 days preceding day 0

◦ Use of parenteral antimicrobial agents within 60 days preceding day 0

◦ Serological evidence of viral hepatitis defined as: patients positive for HbsAg or HbcAb, or hepatitis C antibody positivity, not treated with antiviral medication

• Having a historically positive HIV test or test positive at screening

• Having a history of a primary immunodeficiency

• Having a neutrophil count of < 1.5 × 10⁹/L

• Having a significant infection history that in the opinion of the investigator makes the candidate unsuitable for the study

• Having a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies

• Having any other clinically significant abnormal laboratory value that in the opinion of the investigator makes the candidate unsuitable for the study

• Drug or alcohol abuse or dependence within 1 year preceding day 0

• Having an active malignant neoplasm or one in the last 5 years, except basal cell or squamous cell carcinoma of the skin treated with local resection only, or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years

• Having evidence of serious suicide risk, including suicidal behavior in the last 6 months and/or any suicidal ideation in the last 2 months