What are the treatment options for lupus?

Treatment Options for Lupus

Hydroxychloroquine is the cornerstone of lupus treatment and should be used in all patients unless contraindicated, as it reduces disease flares, mortality, and improves quality of life. 1, 2, 3

Foundation Therapy for All Lupus Patients

• Hydroxychloroquine at doses not exceeding 5 mg/kg actual body weight (typically 200-400 mg daily) forms the basis of treatment for all lupus manifestations and has been associated with significant mortality reduction 1, 2, 3
• Ophthalmological screening is mandatory at baseline, after 5 years, then yearly to monitor for retinal toxicity 1
• Broad-spectrum sunscreen and ultraviolet light avoidance are beneficial for cutaneous manifestations 4, 1

Treatment Based on Disease Severity

Mild to Moderate Disease (Mucocutaneous, Musculoskeletal)

For mild disease, hydroxychloroquine combined with NSAIDs and low-dose glucocorticoids (≤7.5 mg/day prednisone equivalent) should be used. 5, 1

• NSAIDs serve as first-line for pain and stiffness, particularly musculoskeletal symptoms 5
• For patients with gastrointestinal risk, use non-selective NSAIDs plus proton pump inhibitor or selective COX-2 inhibitor 5
• Topical glucocorticoids are the mainstay for localized cutaneous manifestations 1
• For refractory cutaneous disease, add methotrexate, dapsone (particularly for bullous lupus), or mycophenolate mofetil 1

Moderate to Severe Disease Without Nephritis

When hydroxychloroquine and low-dose glucocorticoids are insufficient, add immunosuppressive agents: mycophenolate mofetil (750-1000 mg twice daily), azathioprine, or methotrexate. 6, 3

• Mycophenolate mofetil is preferred for most patients with moderate to severe disease 6, 3
• Azathioprine is the alternative for patients planning pregnancy or intolerant to mycophenolate 6
• Glucocorticoids should be tapered to <7.5 mg/day and withdrawn when possible 6, 1

Active Class III/IV Lupus Nephritis

For proliferative lupus nephritis, initiate glucocorticoids plus one of four regimens: (1) mycophenolic acid analogs, (2) low-dose IV cyclophosphamide, (3) belimumab with either mycophenolic acid or cyclophosphamide, or (4) mycophenolic acid plus calcineurin inhibitor when eGFR >45 ml/min/1.73m². 4

Initial Therapy Selection Algorithm:

• Mycophenolic acid-based regimen is preferred for patients at high infertility risk (prior cyclophosphamide exposure) 4
• IV cyclophosphamide is preferred for patients with adherence concerns to oral regimens 4
• Calcineurin inhibitor (voclosporin, tacrolimus, cyclosporine) plus mycophenolic acid is preferred when eGFR >45 ml/min/1.73m² with nephrotic-range proteinuria due to podocyte injury 4
• Triple therapy with belimumab plus glucocorticoids and either mycophenolic acid or cyclophosphamide is preferred for repeated kidney flares or high progression risk 4

Glucocorticoid Dosing for Lupus Nephritis:

The reduced-dose scheme is preferred when kidney and extrarenal manifestations show satisfactory improvement 4:

• Weeks 0-2: 0.5-0.6 mg/kg/day (max 40 mg), often preceded by methylprednisolone IV pulses 0.25-0.5 g/day for up to 3 days 4
• Taper progressively to <2.5 mg/day by week 25 4

Maintenance Therapy for Lupus Nephritis:

After completing initial therapy, continue mycophenolic acid (mycophenolate mofetil 750-1000 mg twice daily or mycophenolic acid 540-720 mg twice daily) for maintenance. 4

• Total duration of initial plus maintenance immunosuppression should be ≥36 months 4, 6
• Azathioprine is an alternative for patients intolerant to mycophenolic acid or planning pregnancy 4
• Patients on triple therapy with belimumab or calcineurin inhibitors can continue these agents during maintenance 4

Biologic Therapies for Refractory Disease

Belimumab is FDA-approved for active SLE (2011) and lupus nephritis (2020) and should be added for patients with inadequate response to standard therapy. 7, 3

• Belimumab demonstrated efficacy in autoantibody-positive SLE patients when added to standard therapy 7
• Rituximab should be considered for persistent disease activity or inadequate response to initial standard-of-care therapy 4, 6
• Anifrolumab is FDA-approved for active SLE 3, 8
• Voclosporin is FDA-approved specifically for lupus nephritis 3, 8

Treatment Response Assessment

Complete response is defined as proteinuria <0.5 g/g with stable/improved kidney function within 6-12 months; partial response requires ≥50% proteinuria reduction to <3 g/g with stable/improved kidney function. 6

• Switch to alternative agent if no improvement within 3-4 months, no partial response after 6-12 months, or no complete response after 2 years 6
• Monitor disease activity every 2-4 weeks initially after treatment changes 6

Critical Adjunctive Measures

All lupus patients require comprehensive preventive strategies 4:

• Infection prevention: Screen for hepatitis B/C, HIV, tuberculosis, herpes zoster; provide HBV vaccination; consider Pneumocystis jirovecii prophylaxis and recombinant zoster vaccine 4
• Bone protection: Assess bone mineral density and fracture risk; provide calcium, vitamin D, and bisphosphonates when appropriate 4
• Fertility preservation: Consider gonadotropin-releasing hormone agonists (leuprolide) and sperm/oocyte cryopreservation before cyclophosphamide; minimize lifetime cyclophosphamide exposure to <36 g 4
• Contraception counseling: Individualized evaluation considering thrombosis risk, particularly with antiphospholipid antibodies 4

Common Pitfalls to Avoid

• Never exceed hydroxychloroquine dose of 5 mg/kg actual body weight to minimize retinopathy risk 1, 2
• Avoid prolonged high-dose glucocorticoids (>7.5 mg/day) as they increase irreversible organ damage 5, 1
• NSAIDs require close monitoring in lupus nephritis due to increased acute renal failure risk 9
• Mycophenolate mofetil, cyclophosphamide, and methotrexate are contraindicated in pregnancy; use prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin instead 1
• Always assess medication adherence, especially hydroxychloroquine, as non-adherence increases flare rates 5