Treatment of Systemic Lupus Erythematosus (SLE) With N-acetylcysteine

Inclusion Criteria:

• Age ≥ 18;

• Male or female;

• ≥ 4 ACR SLE classification criteria (104,105);

• Positive ANA at a titer of ≥ 1/80;

• Stable immunosuppressants (MMF ≤ 3 g/day, azathioprine ≤ 150 mg/day; methotrexate ≤ 25 mg/week; leflunomide ≤ 20 mg/week; cyclosporin 100 mg/day; voclosporin 47.4 mg/day) and/or antimalarials (hydroxychloroquine ≤ 400 mg/day) for 30 days prior to screening; stable oral corticosteroids for 2 weeks prior to screening; ≤ 20 mg/day prednisone or equivalent; stable belimumab or anifrolumab for 90 days prior to screening;

• BILAG 2004 index (48) level A disease activity in ≥ 1 organ/system except renal or central nervous system or BILAG 2004 index level B disease activity in ≥ 1 organs/systems if no level A disease activity is present and SLEDAI ≥ 6 (106);

• Enrollment is approved by adjudication committee within 10 days, which may include retesting and communication with study sites, as necessary.

• Patients may be considered for enrollment 12 months after rituximab treatment, or 6 months after rituximab treatment if their B cell counts have normalized.

Participant Exclusion Criteria

• Acute SLE flare threatening vital organs;

• Pregnant or lactating;

• Moderately serious or serious comorbidities (e.g., diabetes mellitus, congestive heart failure, chronic obstructive pulmonary disease, chronic renal insufficiency) that in investigator's opinion confers high risk for adverse events;

• Patients receiving cyclophosphamide within 3 months;

• Active chronic infections (e.g., HIV, hepatitis B virus, hepatitis C virus, mycobacteria); patients with oral steroid-dependent asthma;

• Infections requiring intravenous antibiotics within a month or oral antibiotics within two weeks of screening; Patients taking (unwilling or unable to stop) NAC or other antioxidants within 1 month of screening (which is considered sufficient time to revert GSH to pre-treatment levels (29);

• Patients who participated in the pilot RCT or are taking daily acetaminophen (≤ 1 g/day prn is allowed if documented);

• Patients receiving mTOR inhibitors (rapamycin/sirolimus, everolimus);

• Patients enrolled in other interventional trials.

• Patients should not take medications containing acetaminophen (Tylenol) as it may reduce the effectiveness of NAC. 1 g/day of acetaminophen is allowed if documented.

• Patients should avoid taking more than 500 mg of vitamin C and more than 30 IU of vitamin E daily as both vitamin C and E can confound the study results.