What is the recommended treatment regimen for systemic lupus erythematosus (SLE)?

Treatment Regimen for Systemic Lupus Erythematosus

All patients with SLE should receive hydroxychloroquine at a dose not exceeding 5 mg/kg real body weight as the backbone of therapy, combined with glucocorticoid minimization to less than 7.5 mg/day (prednisone equivalent) during chronic maintenance, with early addition of immunomodulatory agents (methotrexate, azathioprine, or mycophenolate) to expedite steroid tapering. 1, 2

Universal Baseline Treatment

• Hydroxychloroquine is mandatory for all SLE patients at 200-400 mg daily (not exceeding 5 mg/kg actual body weight), as this reduces disease activity, morbidity, and mortality 1, 2, 3
• Administer with food or milk; do not crush or divide tablets 2
• Ophthalmological screening should be performed at baseline, after 5 years, and yearly thereafter 4

Glucocorticoid Strategy

Acute/Severe Disease

• For severe or organ-threatening manifestations, administer intravenous methylprednisolone pulses (250-1000 mg per day for 1-3 days) 5
• Initial oral prednisone at 0.5-1 mg/kg/day for acute control, with subsequent tapering 5

Chronic Maintenance

• Target prednisone dose of less than 7.5 mg/day (preferably ≤5 mg/day) with the goal of complete withdrawal 1, 6
• Stable maintenance doses of 200 mg/day hydroxychloroquine combined with prednisone ≤5-2.5 mg/day accomplish disease control without compromising long-term safety 6

Immunomodulatory/Immunosuppressive Agents

Mild to Moderate Disease (Musculoskeletal/Cutaneous)

• If hydroxychloroquine and low-dose glucocorticoids fail, add methotrexate, azathioprine, or mycophenolate 1
• Cost and availability favor methotrexate and azathioprine in resource-limited settings 1

Persistently Active or Flaring Extrarenal Disease

• Add belimumab for persistently active or flaring disease despite standard therapy 1, 5
• Consider rituximab for organ-threatening, refractory disease 1, 5
• Cyclophosphamide can be used for severe organ-threatening disease or as "rescue" therapy 5, 4

Lupus Nephritis Treatment Algorithm

Induction Therapy

• Glucocorticoids plus an immunosuppressant (cyclophosphamide in high or low doses, mycophenolate, or tacrolimus) over glucocorticoids alone 1
• Low-dose cyclophosphamide has comparable efficacy to high-dose with better safety profile 1
• Mycophenolate and tacrolimus are associated with fewer adverse effects than high-dose cyclophosphamide 1
• Limited access to mycophenolate and tacrolimus in Latin America makes cyclophosphamide the preferred alternative due to cost 1

Maintenance Therapy

• After achieving partial or complete remission, use azathioprine or mycophenolate for maintenance 1
• Continue hydroxychloroquine and minimize glucocorticoids to less than 7.5 mg/day 1

Pulmonary Involvement

SLE-Associated Interstitial Lung Disease

• First-line options: mycophenolate, azathioprine, rituximab, or cyclophosphamide 4
• For progression despite first-line therapy, switch to or add mycophenolate, rituximab, or cyclophosphamide 4
• For rapidly progressive ILD, pulse intravenous methylprednisolone is first-line 4

Treatment Goals and Monitoring

Primary Objectives

• Achieve remission or low disease activity in all organ systems 1, 5, 3
• Prevent disease flares and minimize glucocorticoid exposure 1, 5
• Reduce disease exacerbations, hospitalizations, and organ damage 3

Monitoring Parameters

• Regular assessment using validated indices (BILAG index) 5
• Monitor complement levels (C3, C4) and anti-dsDNA antibodies 5, 4
• Screen for infections, a common complication of immunosuppressive therapy 5, 4
• Assess cardiovascular disease and antiphospholipid antibody status 1

Critical Pitfalls to Avoid

• Never exceed 5 mg/kg actual body weight for hydroxychloroquine, as higher doses increase retinopathy risk 1, 2
• Avoid prolonged high-dose glucocorticoids; early addition of immunomodulatory agents expedites steroid tapering 1, 5
• Do not use hydroxychloroquine on alternate days; maintain consistent daily dosing 2
• Rituximab combined with mycophenolate did not provide additional benefits over mycophenolate alone in lupus nephritis 1