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

Treatment of Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine at a dose not exceeding 5 mg/kg real body weight is the cornerstone of 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 ≤5 mg/kg real body weight daily, serving as the backbone of treatment regardless of disease severity 1, 2
• 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

The goal is to minimize chronic glucocorticoid exposure to <7.5 mg/day prednisone equivalent and withdraw when possible to prevent organ damage. 1

• For acute flares: Intravenous methylprednisolone pulses provide immediate effect and enable lower starting oral doses 1
• Doses and routes depend on organ involvement severity 1
• Chronic maintenance must be minimized to <7.5 mg/day and withdrawn when feasible 1

Mild-to-Moderate Disease (Musculoskeletal, Cutaneous)

• NSAIDs for intermittent joint pain and serositis, used in up to 80% of patients for musculoskeletal symptoms 3, 4
• Methotrexate for skin and joint manifestations refractory to hydroxychloroquine 1, 5
• Topical glucocorticoids as mainstay for localized cutaneous manifestations 5
• Topical calcineurin inhibitors for localized cutaneous disease 5

Moderate-to-Severe Disease Requiring Immunosuppression

When patients fail to respond to hydroxychloroquine alone or cannot reduce glucocorticoids below 7.5 mg/day, add immunosuppressive agents. 1

Selection Algorithm:

• Mycophenolate mofetil: For renal and non-renal manifestations (except neuropsychiatric disease) 1, 6
• Azathioprine: For maintenance therapy, particularly suitable for women contemplating pregnancy 1, 5
• Cyclophosphamide: Reserved for severe organ-threatening disease (renal, cardiopulmonary, or neuropsychiatric) 1, 6

Organ-Specific Treatment Protocols

Lupus Nephritis

Kidney biopsy is essential before initiating treatment. 1

• Induction therapy: Mycophenolate mofetil or cyclophosphamide are first-line agents 1
• Low-dose cyclophosphamide is preferred over high-dose due to comparable efficacy with lower gonadotoxicity 1
• Maintenance therapy: Mycophenolate mofetil or azathioprine 1

Neuropsychiatric Lupus (NPSLE)

Treatment depends on the underlying pathophysiological mechanism—inflammatory versus thrombotic. 1

• For inflammatory mechanisms: High-dose glucocorticoids (IV methylprednisolone) plus cyclophosphamide, with response rates of 18/19 patients versus 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: Combination of immunosuppressive and anticoagulant therapy 1

Hematological Manifestations (Thrombocytopenia)

• First-line: Moderate/high-dose glucocorticoids combined with immunosuppressive agents (azathioprine, mycophenolate mofetil, or cyclosporine) 1
• Initial therapy with IV methylprednisolone pulses 1
• IVIG for acute phase or inadequate glucocorticoid response 1
• Refractory cases: Rituximab or cyclophosphamide 1

Serositis (Pericarditis/Pleuritis)

• Colchicine combined with standard therapy decreases pericarditis recurrence 3
• NSAIDs for pain control 3

Biologic Therapies for Refractory Disease

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

FDA-Approved Biologics:

• Belimumab (anti-BAFF antibody): For active extrarenal SLE and lupus nephritis 1, 7
• Anifrolumab (anti-type 1 interferon receptor): For moderate-to-severe extrarenal SLE 1
• Voclosporin: For lupus nephritis 1
• Rituximab: For refractory cases, particularly hematological manifestations 1

Critical Monitoring Requirements

Monitor disease activity at every visit using validated indices (BILAG, ECLAM, or SLEDAI). 1, 3

• Laboratory monitoring: Anti-dsDNA, C3, C4, complete blood count, creatinine, proteinuria, and urine sediment 1
• SLE patients have 5-fold increased mortality risk requiring screening for: 1
  • Infections
  • Cardiovascular disease, hypertension, diabetes, dyslipidemia
  • Osteoporosis
  • Malignancies (especially non-Hodgkin lymphoma)

Special Population: Pregnancy

Safe medications during pregnancy include prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin. 1

• Contraindicated: Mycophenolate mofetil, cyclophosphamide, and methotrexate 1

Common Pitfalls to Avoid

• Never exceed 5 mg/kg real body weight for hydroxychloroquine, as daily doses exceeding this increase retinopathy incidence 1, 2
• Avoid chronic glucocorticoid doses ≥7.5 mg/day to prevent organ damage 1
• Do not use NSAIDs without monitoring renal function, as lupus nephritis is a risk factor for NSAID-induced acute renal failure 4
• Never delay kidney biopsy in suspected lupus nephritis, as it is essential for diagnosis and treatment planning 1