What are the treatment options for Systemic Lupus Erythematosus (SLE)?

Treatment of Systemic Lupus Erythematosus

Hydroxychloroquine at ≤5 mg/kg real body weight is the cornerstone therapy for all SLE patients and should be initiated immediately, as it reduces disease activity, prevents flares, and improves survival. 1

Universal Foundation Therapy (All SLE Patients)

• Hydroxychloroquine is mandatory for all patients at doses not exceeding 5 mg/kg real body weight 1
• Ophthalmological screening is required at baseline, after 5 years, then yearly to monitor for retinal toxicity 1
• Photoprotection with sunscreens prevents cutaneous flares 1
• Low-dose aspirin for patients with antiphospholipid antibodies, those receiving corticosteroids, or those with cardiovascular risk factors 1
• Calcium and vitamin D supplementation for all patients on long-term glucocorticoids 1

Glucocorticoid Strategy

Acute Flares

• Intravenous methylprednisolone pulses (500-1000 mg/day for 1-3 days) provide immediate therapeutic effect and enable lower starting doses of oral glucocorticoids 1, 2
• Expected response within 24-48 hours 2

Chronic Maintenance

• Minimize to <7.5 mg/day prednisone equivalent and withdraw when possible to prevent organ damage 1, 2
• This is a critical target to reduce long-term complications 1

Second-Line Immunosuppressive Agents

Add these when patients fail hydroxychloroquine alone or cannot reduce glucocorticoids below acceptable chronic doses 1:

• Methotrexate: for skin and joint manifestations 1
• Azathioprine: for maintenance therapy, particularly suitable for women contemplating pregnancy 1
• Mycophenolate mofetil: for renal and non-renal manifestations (except neuropsychiatric disease) 1
• Cyclophosphamide: for severe organ-threatening disease (especially renal, cardiopulmonary, or neuropsychiatric) 1

Organ-Specific Treatment Algorithms

Lupus Nephritis

• Kidney biopsy is mandatory for diagnosis and treatment planning 1
• Induction therapy: Mycophenolate mofetil or cyclophosphamide are the immunosuppressive agents of choice 1
• Low-dose cyclophosphamide is preferred over high-dose due to comparable efficacy and lower gonadotoxicity 1
• Maintenance therapy: Mycophenolate mofetil or azathioprine 1

Neuropsychiatric Lupus (NPSLE)

For inflammatory/immune-mediated mechanisms:

• High-dose intravenous methylprednisolone plus cyclophosphamide (response rate 18/19 patients vs 7/13 with methylprednisolone alone, p=0.03) 1

For thrombotic/embolic mechanisms:

• Anticoagulation with warfarin: target INR 2.0-3.0 for first venous thrombosis; INR 3.0-4.0 for arterial or recurrent thrombosis 1, 2

When both mechanisms coexist:

• Combination of immunosuppressive and anticoagulant therapy 1, 2

Hematological Manifestations (Severe Thrombocytopenia <30,000/mm³)

• Initial therapy: Intravenous methylprednisolone pulses (1-3 days) plus immunosuppressive agent (azathioprine, mycophenolate mofetil, or cyclosporine) 1, 2
• IVIG may be considered in the acute phase or with inadequate response to glucocorticoids 1, 2
• Refractory cases: Rituximab or cyclophosphamide 1

Gastrointestinal Bleeding

• Determine the mechanism: differentiate between inflammatory mesenteric vasculitis versus thrombosis/ischemia related to antiphospholipid antibodies 2
• For inflammatory vasculitis: High-dose methylprednisolone pulses (500-1000 mg/day for 1-3 days) with expected response within 24-48 hours, followed by moderate to high doses of oral prednisone (0.5-1 mg/kg/day) 2
• Add cyclophosphamide for severe disease with vital risk, or consider mycophenolate mofetil or azathioprine 2

Musculoskeletal Pain

• NSAIDs are appropriate for intermittent joint pain, with up to 80% of lupus patients receiving them 3
• Hydroxychloroquine remains the foundation, combined with NSAIDs for acute symptoms and low-dose glucocorticoids for persistent pain 3

Serositis (Pericarditis/Pleuritis)

• Colchicine combined with standard therapy decreases pericarditis recurrence rate 3

Cutaneous Manifestations

• Topical glucocorticoids are the mainstay for localized disease 3
• Mycophenolate mofetil is effective for refractory cutaneous disease 3

FDA-Approved Biologic Therapies for Refractory Disease

Consider biologics when patients have inadequate response to standard therapy 1:

• Belimumab (anti-BAFF antibody): approved for active extrarenal SLE and lupus nephritis 1, 4
• Anifrolumab (anti-type 1 interferon receptor): approved for moderate-to-severe extrarenal SLE 1
• Voclosporin: approved for lupus nephritis 1
• Rituximab: may be considered for refractory cases, particularly hematological manifestations 1

Critical Monitoring Requirements

• At each visit: Use validated activity indices (BILAG, ECLAM, or SLEDAI) 1, 3
• Laboratory monitoring: anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment 1, 3
• Comorbidity screening: SLE patients have a 5-fold increased mortality risk; screen for infections, cardiovascular disease, hypertension, diabetes, dyslipidemia, osteoporosis, and malignancies (especially non-Hodgkin lymphoma) 1

Special Populations: Pregnancy

Safe medications:

• Prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin 1

Contraindicated medications:

• Mycophenolate mofetil, cyclophosphamide, and methotrexate 1

Common Pitfalls to Avoid

• Never withhold hydroxychloroquine unless there is a specific contraindication—it is the foundation of all SLE therapy 1
• Do not use chronic glucocorticoids ≥7.5 mg/day without adding steroid-sparing immunosuppressive agents to prevent organ damage 1, 2
• Do not delay kidney biopsy in suspected lupus nephritis—it is essential for treatment planning 1
• Do not assume all NPSLE is inflammatory—differentiate between inflammatory and thrombotic mechanisms as treatment differs fundamentally (immunosuppression vs anticoagulation) 1, 2
• Do not use mycophenolate mofetil in women of childbearing potential without adequate contraception or pregnancy planning 1