What is the overview of Systemic Lupus Erythematosus (SLE) treatment?

Overview of Systemic Lupus Erythematosus (SLE) Treatment

Hydroxychloroquine is the cornerstone therapy for all SLE patients at doses not exceeding 5 mg/kg real body weight, combined with glucocorticoids tailored to organ involvement severity, with the goal of achieving remission or low disease activity while minimizing steroid exposure to less than 7.5 mg/day. 1, 2, 3

Foundation Therapy for All Patients

• Hydroxychloroquine (HCQ) is FDA-approved and recommended for all SLE patients unless contraindicated, as it reduces disease activity, prevents flares, and improves survival 1, 3
• The dose must not exceed 5 mg/kg of real body weight to minimize retinal toxicity risk 1
• Ophthalmological screening is mandatory at baseline, after 5 years, then yearly thereafter 1
• Photoprotection with sunscreens prevents cutaneous flares 1
• Low-dose aspirin should be given to patients with antiphospholipid antibodies, those receiving corticosteroids, or those with cardiovascular risk factors 1
• Calcium and vitamin D supplementation is required for all patients on long-term glucocorticoids 1

Glucocorticoid Management

• For acute flares, intravenous methylprednisolone pulses (250-1000 mg/day for 1-3 days) provide immediate therapeutic effect and enable lower starting doses of oral steroids 1, 4
• Initial oral prednisone dosing ranges from 0.5-1 mg/kg/day depending on severity, followed by aggressive tapering 4
• Chronic maintenance glucocorticoid therapy must be minimized to less than 7.5 mg/day and withdrawn when possible to prevent organ damage 1, 2

Immunosuppressive Therapy

When patients fail to respond adequately to HCQ alone or cannot taper glucocorticoids below acceptable chronic doses, add immunosuppressive agents 1, 2:

• Methotrexate for skin and joint manifestations 1
• Azathioprine for maintenance therapy, particularly suitable for women contemplating pregnancy 1, 2
• Mycophenolate mofetil (MMF) for renal and non-renal manifestations except neuropsychiatric disease 1, 2
• Cyclophosphamide for severe organ-threatening disease, especially renal, cardiopulmonary, or neuropsychiatric manifestations 1

Organ-Specific Treatment Algorithms

Lupus Nephritis

• Kidney biopsy is essential before initiating therapy 1, 2
• Induction therapy: MMF or low-dose cyclophosphamide (preferred over high-dose due to comparable efficacy with lower gonadotoxicity) 1
• Maintenance therapy: MMF or azathioprine 1
• Target at least partial remission (≥50% reduction in proteinuria to subnephrotic levels with serum creatinine within 10% of baseline) within 6-12 months 2

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
• When both mechanisms coexist, combine immunosuppressive and anticoagulant therapy 1

Hematological Manifestations

• For significant thrombocytopenia: initial pulse IV methylprednisolone followed by moderate/high-dose glucocorticoids combined with immunosuppressive agents (azathioprine, MMF, or cyclosporine) 1, 2
• IVIG may be added in the acute phase or with inadequate glucocorticoid response 1
• For refractory cases: rituximab or cyclophosphamide 1

Cutaneous Manifestations

• First-line therapy includes topical glucocorticoids and hydroxychloroquine 2

Biologic Therapies for Refractory Disease

When standard therapy fails, biologics should be considered 1:

• Belimumab (anti-BAFF antibody) is FDA-approved for active extrarenal SLE in patients ≥5 years old receiving standard therapy, and for active lupus nephritis 1, 5
• Anifrolumab (anti-type 1 interferon receptor) is FDA-approved for moderate-to-severe extrarenal SLE 1
• Voclosporin is FDA-approved for lupus nephritis 1
• Rituximab may be considered for refractory cases, particularly hematological manifestations, though not FDA-approved for SLE 1, 4

Monitoring and Comorbidity Prevention

• Use validated activity indices (such as BILAG) at each visit 1, 4
• Monitor anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment regularly 1, 4
• SLE patients have 5-fold increased mortality risk; screen aggressively for infections, cardiovascular disease, hypertension, diabetes, dyslipidemia, osteoporosis, avascular necrosis, and malignancies (especially non-Hodgkin lymphoma) 6, 1

Pregnancy Considerations

• Safe medications during pregnancy: prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin 1, 2
• Contraindicated medications: mycophenolate mofetil, cyclophosphamide, and methotrexate 1
• Patients with lupus nephritis and antiphospholipid antibodies require close monitoring for preeclampsia 2
• Pregnancy can increase disease activity, though flares are usually mild 2

Common Pitfalls to Avoid

• Overreliance on corticosteroids contributes to long-term organ damage; aggressively pursue steroid-sparing strategies 7
• NSAIDs should only be used judiciously for limited periods in patients at low risk for complications 6
• Do not use belimumab for severe active CNS lupus, as efficacy has not been established 5
• Failure to perform kidney biopsy before treating lupus nephritis leads to suboptimal therapy selection 1, 2