What are the treatment options for lupus?

Treatment Options for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine should be the foundation of treatment for all patients with lupus, unless contraindicated, as it reduces disease activity, flares, organ damage, and mortality. 1, 2

First-Line Therapy

• Antimalarials (primarily hydroxychloroquine) at a dose not exceeding 5 mg/kg real body weight should be used in all SLE patients 1, 2
• Regular ophthalmological screening should be performed at baseline, after 5 years, and yearly thereafter to monitor for retinal toxicity 1
• NSAIDs can be used for fever, arthritis, serositis, and headaches, but require close monitoring due to increased risk of side effects in lupus patients 3, 4
• Topical glucocorticoids are the mainstay of initial treatment for localized cutaneous lupus manifestations 1

Treatment Based on Disease Severity

Mild Disease (Without Major Organ Involvement)

• Hydroxychloroquine (200-400 mg daily) as the cornerstone of treatment 2
• Low-dose glucocorticoids (≤7.5 mg/day prednisone equivalent) for symptomatic relief 5, 1
• NSAIDs for musculoskeletal symptoms, with caution in patients with renal involvement 3, 6

Moderate to Severe Disease (With Major Organ Involvement)

For Lupus Nephritis:

• Mycophenolate mofetil (MMF) or low-dose intravenous cyclophosphamide plus glucocorticoids is recommended as first-line treatment 5
• Initial MMF dose is typically 3 g/day for 6 months, followed by maintenance dose of 1-2 g/day 5, 7
• Maintenance therapy with MMF (750-1000 mg twice daily) should continue for at least 36 months after completion of initial therapy 5, 7
• Azathioprine is an alternative to MMF after completion of initial therapy in patients who do not tolerate MMF or are considering pregnancy 5, 7

For Refractory Disease:

• Belimumab with glucocorticoids and either MMF or reduced-dose cyclophosphamide may benefit patients with repeated kidney flares or high risk for progression to kidney failure 5, 7, 8
• Rituximab should be considered for patients with persistent disease activity or inadequate response to standard therapies 5, 7
• Calcineurin inhibitors (voclosporin, tacrolimus, or cyclosporine) may be preferred in patients with preserved kidney function and nephrotic-range proteinuria 5, 7

Glucocorticoid Management

• Glucocorticoids should be used at the lowest possible dose and for the shortest period of time 5, 1
• Initial treatment may include three consecutive pulses of intravenous methylprednisolone 500–750 mg, followed by oral prednisone 0.5 mg/kg/day for 4 weeks 5
• Taper to ≤10 mg/day by 4–6 months and aim for <5 mg/day for long-term maintenance 5
• Consider discontinuation of glucocorticoids after patients have maintained a complete clinical renal response for ≥12 months 5

Monitoring Disease Activity

• Regular monitoring should include clinical signs (skin lesions, arthritis, serositis, neurological manifestations) and laboratory tests (complete blood count, serum creatinine, proteinuria, urine sediment, C3, anti-dsDNA) 1
• Visits should be scheduled every 2-4 weeks for the first 2-4 months after diagnosis or flare, and then according to response to treatment 5, 7
• Complete response is defined as reduction in proteinuria <0.5 g/g with stable or improved kidney function within 6-12 months of starting therapy 5, 7
• Partial response is defined as reduction in proteinuria by at least 50% and to <3 g/g with stable or improved kidney function 5, 7

Adjunctive Treatments

• Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are indicated for patients with proteinuria or hypertension 5
• Cholesterol-lowering with statins is indicated for persistent dyslipidemia 5
• Low-dose aspirin may be considered for patients with antiphospholipid antibodies 5, 1
• Calcium and vitamin D supplementation and immunizations with non-live vaccines should be considered 5

Special Considerations

Pregnancy

• Prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin may be used during pregnancy 1
• Mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided during pregnancy 1
• Women planning pregnancy should switch from MMF to azathioprine at least 3 months prior to conception 5

Comorbidity Management

• Patients with SLE have increased risk for infections, atherosclerosis, hypertension, dyslipidemias, diabetes, osteoporosis, avascular necrosis, and malignancies 1
• Minimize risk factors through regular screening and prompt treatment of comorbidities 1

Common Pitfalls to Avoid

• Failure to prescribe hydroxychloroquine to all eligible patients, which is associated with higher rates of flares and organ damage 1, 9
• Prolonged use of high-dose glucocorticoids (>7.5 mg/day prednisone equivalent), which increases risk of irreversible organ damage 5, 3
• Inadequate monitoring of medication side effects, particularly hydroxychloroquine retinal toxicity and immunosuppressant-related infections 1, 2
• Delayed recognition of disease flares or inadequate response to treatment, which should prompt consideration of alternative therapies 7, 10
• Insufficient duration of immunosuppressive therapy for lupus nephritis, which should be at least 36 months of combined initial and maintenance therapy 5