What are the treatment options for lupus?

Treatment Options for Lupus

All patients with systemic lupus erythematosus should receive hydroxychloroquine as the foundation of therapy unless absolutely contraindicated, combined with the lowest possible dose of glucocorticoids and organ-specific immunosuppressive agents based on disease manifestations. 1, 2

Universal Baseline Therapy

Hydroxychloroquine (Antimalarials)

• Hydroxychloroquine is mandatory for all lupus patients and should be prescribed at 200-400 mg daily (not exceeding 5 mg/kg actual body weight) 1, 2
• This medication reduces disease flares, prevents organ damage, and significantly decreases mortality 1, 3, 4
• Requires baseline ophthalmological examination, then annual screening after 5 years of treatment to monitor for retinal toxicity 3, 2
• Can be safely continued during pregnancy 3

Glucocorticoid Management

• When clinically necessary, initiate at the lowest effective dose and taper aggressively 1
• Target maintenance dose is ≤7.5 mg/day prednisone equivalent, with complete withdrawal as the ultimate goal 1, 3
• For active disease, consider initial pulse methylprednisolone 500-750 mg IV for 3 consecutive days, followed by oral prednisone 0.5 mg/kg/day, tapering to ≤10 mg/day by 4-6 months 1

Organ-Specific Treatment Algorithms

Lupus Nephritis (Class III/IV Proliferative)

Initial Therapy (First 6 months):

• First-line: Mycophenolate mofetil 2-3 g/day (or mycophenolic acid 1.44-2.16 g/day) plus glucocorticoids 1
• Alternative: Low-dose intravenous cyclophosphamide (Euro-Lupus regimen: 500 mg IV every 2 weeks for 6 doses) plus glucocorticoids 1
• For patients with preserved kidney function and nephrotic-range proteinuria: Consider calcineurin inhibitors (voclosporin, tacrolimus) 1
• For high-risk patients (repeated flares, severe CKD): Triple therapy with belimumab + glucocorticoids + mycophenolate or reduced-dose cyclophosphamide 1

Maintenance Therapy (≥36 months total duration):

• Continue mycophenolate mofetil 750-1000 mg twice daily (or mycophenolic acid 540-720 mg twice daily) 1
• Alternative: Azathioprine 2 mg/kg/day (especially if planning pregnancy) 1
• Taper glucocorticoids to ≤5-7.5 mg/day; consider discontinuation after 12 months of complete remission 1

Refractory Disease:

• Switch from mycophenolate to cyclophosphamide, or vice versa 1
• Add rituximab for persistent activity despite standard therapy 1, 5

Mucocutaneous Manifestations

Mild-to-Moderate Disease:

• Topical glucocorticoids for localized lesions 3
• Hydroxychloroquine 200-400 mg daily (already prescribed as baseline therapy) 3
• Strict photoprotection with high-SPF sunscreen 1, 3

Moderate-to-Severe or Refractory Disease:

• Methotrexate 15-25 mg weekly for widespread cutaneous disease 3
• Mycophenolate mofetil 1-3 g/day for refractory cases 3
• Dapsone 50-100 mg daily specifically for bullous lupus or urticarial vasculitis 3
• Belimumab or rituximab for cases unresponsive to standard immunosuppressives 3, 6

Musculoskeletal Manifestations

Arthritis and Arthralgia:

• NSAIDs as first-line for pain and stiffness, but use cautiously 7, 8, 9
• Monitor closely for NSAID-induced renal toxicity, especially in patients with lupus nephritis 8, 9
• Consider selective COX-2 inhibitors with gastroprotection for patients at GI risk 7
• Methotrexate 15-25 mg weekly for persistent arthritis 3
• Local corticosteroid injections for specific joint involvement 7

Hematologic Manifestations

Cytopenias:

• Moderate disease: Azathioprine 2 mg/kg/day or mycophenolate mofetil 2-3 g/day 1
• Severe disease: High-dose glucocorticoids with or without intravenous immunoglobulin 1
• Refractory cases: Rituximab or cyclophosphamide 1

Biologic Therapies

Belimumab

• FDA-approved for active SLE (2011) and lupus nephritis (2020) 6, 4
• Indicated for autoantibody-positive patients with inadequate response to standard therapy 6
• Administered as 10 mg/kg IV at weeks 0,2,4, then every 4 weeks 6
• Can be added to standard immunosuppressive regimens for high-risk lupus nephritis 1, 5

Rituximab

• Reserved for refractory disease unresponsive to standard immunosuppressives 1, 5
• Particularly useful for severe hematologic manifestations or refractory lupus nephritis 5

Adjunctive Therapies

Cardiovascular and Thrombosis Prevention

• ACE inhibitors or ARBs for all patients with proteinuria (UPCR >50 mg/mmol) or hypertension 1
• Low-dose aspirin 75-100 mg daily for patients with antiphospholipid antibodies 1
• Statins for persistent dyslipidemia (target LDL <100 mg/dL) 1

Bone Health

• Calcium and vitamin D supplementation for all patients on chronic glucocorticoids 1

Critical Monitoring Parameters

Every 2-4 weeks during initial treatment, then every 3-6 months:

• Serum creatinine, eGFR, proteinuria (spot urine protein-to-creatinine ratio) 1
• Complete blood count 1
• Complement levels (C3, C4) and anti-dsDNA antibodies 1
• Blood pressure and body weight 1
• Urinalysis with microscopic examination 1

Treatment Response Definitions:

• Complete response: Proteinuria <0.5 g/g with stable/improved kidney function within 6-12 months 1
• Partial response: ≥50% reduction in proteinuria to <3 g/g with stable/improved kidney function 1
• Switch therapy if no improvement by 3-4 months, no partial response by 6-12 months, or no complete response by 24 months 1

Common Pitfalls to Avoid

• Never withhold hydroxychloroquine unless absolute contraindication exists—non-adherence is associated with increased flares and mortality 1, 3
• Avoid prolonged high-dose glucocorticoids (>7.5 mg/day)—this increases irreversible organ damage 1, 7
• Do not use NSAIDs liberally in patients with lupus nephritis—they significantly increase risk of acute renal failure 8, 9
• Avoid mycophenolate, cyclophosphamide, and methotrexate during pregnancy—switch to azathioprine at least 3 months before conception 3
• Do not discontinue immunosuppression prematurely—maintain combination therapy for minimum 36 months in lupus nephritis 1

Special Populations

Pregnancy Planning

• Switch from mycophenolate to azathioprine ≥3 months before conception 1, 3
• Continue hydroxychloroquine, low-dose prednisone (≤20 mg/day), and azathioprine throughout pregnancy 3
• Add low-dose aspirin if antiphospholipid antibodies present 3

Patients at High Risk for Infertility

• Prefer mycophenolate-based regimens over cyclophosphamide 1
• If cyclophosphamide necessary, use Euro-Lupus low-dose protocol (total cumulative dose <6 g) 1