From the Guidelines
Systemic Lupus Erythematosus (SLE) and Lupus Nephritis require a comprehensive treatment approach, with hydroxychloroquine being the cornerstone of therapy for all SLE patients, as recommended by the 2019 EULAR guidelines 1 and further supported by the 2024 KDIGO clinical practice guideline for the management of lupus nephritis 1.
Epidemiology and Basic Pathophysiology
SLE predominantly affects women of childbearing age with a 9:1 female-to-male ratio, with higher prevalence in African Americans, Hispanics, and Asians. The disease involves autoantibody production against nuclear antigens, immune complex formation, and complement activation leading to multi-organ inflammation. Lupus nephritis specifically affects approximately 50% of SLE patients, causing kidney inflammation and potential renal failure.
Risk Factors
Risk factors include female gender, African American or Hispanic ethnicity, family history, certain HLA genotypes, hormonal factors, UV exposure, medications like hydralazine and procainamide, and infections that may trigger autoimmunity.
Screening
Screening involves regular monitoring of patients with SLE for proteinuria, hematuria, rising creatinine, and hypertension to detect early kidney involvement.
Diagnosis
Diagnosis requires clinical evaluation plus laboratory testing including:
- ANA
- anti-dsDNA
- anti-Smith antibodies
- complement levels (C3, C4)
- CBC
- comprehensive metabolic panel
- urinalysis
- urine protein-to-creatinine ratio
- kidney biopsy for lupus nephritis classification
Treatments and Place of Therapy
Treatment begins with hydroxychloroquine (antimalarial, 200-400mg daily) for all SLE patients, requiring ophthalmologic monitoring for retinopathy, as recommended by the 2019 EULAR guidelines 1 and the 2024 KDIGO clinical practice guideline for the management of lupus nephritis 1. For lupus nephritis, medications include:
- belimumab (B-lymphocyte stimulator inhibitor, 10mg/kg IV monthly)
- mycophenolate mofetil (immunosuppressant, 2-3g daily in divided doses)
- cyclophosphamide (alkylating agent, 500-1000mg/m² monthly IV)
- tacrolimus/cyclosporine (calcineurin inhibitors, dosed by levels)
- rituximab (anti-CD20 monoclonal antibody, 375mg/m² weekly for 4 weeks)
- voclosporin (calcineurin inhibitor, 23.7mg BID) All require monitoring for infection, renal/liver function, and specific toxicities.
Supportive Medications
Supportive medications include:
- corticosteroids for flares
- antihypertensives (especially ACE inhibitors/ARBs for proteinuria)
- bone health supplements
- thromboprophylaxis when indicated
Other Counseling Points
Patient counseling should emphasize:
- medication adherence
- sun protection
- infection prevention
- pregnancy planning
- regular monitoring appointments
The use of hydroxychloroquine in SLE patients has been associated with a decrease in lupus activity, lower flare rates, and improved patient outcomes, as supported by the 2019 EULAR guidelines 1 and the 2024 KDIGO clinical practice guideline for the management of lupus nephritis 1.
From the FDA Drug Label
Systemic Lupus Erythematosus/Lupus Nephritis Topic Discussion
Epidemiology/Basic Pathophysiology
- Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can affect various parts of the body, including the skin, joints, kidneys, brain, and other organs.
- Lupus Nephritis is a common complication of SLE, characterized by inflammation of the kidneys.
Risk Factors
- Genetic predisposition: Family history of SLE or other autoimmune diseases.
- Hormonal factors: SLE is more common in women, especially during childbearing years.
- Environmental factors: Exposure to sunlight, infections, and certain medications.
Screening
- No specific screening test for SLE, but patients with symptoms or risk factors may undergo:
- Antinuclear antibody (ANA) test: Positive result indicates autoimmune activity.
- Complete blood count (CBC): To rule out other conditions.
- Urinalysis: To check for kidney damage.
Diagnosis
- American College of Rheumatology (ACR) criteria: Requires at least 4 of 11 criteria, including:
- Malar rash
- Discoid rash
- Photosensitivity
- Oral ulcers
- Arthritis
- Serositis
- Kidney disorder
- Seizures
- Psychosis
- Blood disorders
- Immunological disorders
- SELENA-SLEDAI score: Measures disease activity.
- BILAG index: Assesses organ involvement.
Treatments and Place of Therapy
Belimumab (IV)
The safety and effectiveness of BENLYSTA 10 mg/kg administered intravenously over 1 hour on Days 0,14,28, and then every 28 days plus standard therapy were evaluated in a 104-week, randomized, double‑blind, placebo‑controlled trial in 448 patients with active proliferative and/or membranous lupus nephritis (Trial 5) 2
- Indication: Treatment of adult patients with active lupus nephritis.
- Drug Class: Monoclonal antibody.
- Dose: 10 mg/kg IV every 28 days.
- ADE: Infusion reactions, infections, malignancies.
- Monitoring: Regular infusions, laboratory tests.
- Supportive medications: Standard therapy, including corticosteroids and immunosuppressants.
Other Treatments
- Hydroxychloroquine: Antimalarial medication for mild SLE.
- Mycophenolate mofetil: Immunosuppressant for lupus nephritis.
- Cyclophosphamide: Immunosuppressant for severe lupus nephritis.
- Calcineurin inhibitors: Immunosuppressants for lupus nephritis.
- Rituxan: Monoclonal antibody for refractory SLE.
- Voclosporin: Immunosuppressant for lupus nephritis.
Counseling Points
- Importance of adherence: Regular infusions and medication use.
- Monitoring for side effects: Infusion reactions, infections, malignancies.
- Lifestyle modifications: Sun protection, stress management, regular exercise.
- Pregnancy and breastfeeding: Consult healthcare provider before becoming pregnant or breastfeeding.
From the Research
Epidemiology/Basic Pathophysiology
- Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems, including the mucocutaneous, musculoskeletal, hematologic, and kidney systems 3.
- Approximately 3.4 million people worldwide have received a diagnosis of SLE, with approximately 90% of people with SLE being female 3.
- Lupus nephritis (LN) is a form of glomerulonephritis that constitutes one of the most severe organ manifestations of SLE, with approximately 40% of people with SLE developing LN 3, 4.
Risk Factors
- The exact cause of SLE is unknown, but it is believed to involve a combination of genetic, environmental, and hormonal factors 3.
- People with a family history of SLE or other autoimmune diseases are at increased risk of developing SLE 3.
Screening
- There are no uniformly accepted diagnostic criteria for SLE, but the 2019 European Alliance of Associations for Rheumatology (formerly the European League Against Rheumatism)/American College of Rheumatology classification criteria are an estimated 96.1% sensitive and 93.4% specific for SLE 3.
- These classification criteria include both clinical factors, such as fever, cytopenia, rash, arthritis, and proteinuria, which may be indicative of lupus nephritis, and immunologic measures, such as SLE-specific autoantibodies and low complement levels 3.
Diagnosis
- Diagnosis of SLE is based on a combination of clinical and laboratory findings, including the presence of SLE-specific autoantibodies and low complement levels 3.
- Renal biopsy is indispensable for the management of LN, and is used to confirm the diagnosis and assess the severity of kidney damage 5.
Treatments and Place of Therapy
- The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications 3.
- Hydroxychloroquine is standard of care for SLE and has been associated with a significant reduction in mortality 3.
- Treatments in addition to hydroxychloroquine are individualized, with immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, typically used for treating moderate to severe disease 3.
- Biologic agents, such as belimumab and rituximab, may be used in refractory or organ-threatening disease 6, 3.
- Voclosporin may be considered for patients with heavy proteinuria, in combination with mycophenolate mofetil, for up to 3 years 5.
- The following medications are used to treat SLE and LN:
- Hydroxychloroquine:
- Indication: SLE, LN
- Drug Class: Antimalarial
- Dose: Variable, depending on the patient's weight and disease severity
- ADE: Gastrointestinal upset, skin rash, eye toxicity
- Monitoring: Regular eye exams, complete blood counts
- Belimumab:
- Indication: SLE, LN
- Drug Class: Biologic agent
- Dose: 10 mg/kg intravenously every 2 weeks for the first 3 doses, then every 4 weeks
- ADE: Infusion reactions, infections, gastrointestinal upset
- Monitoring: Regular complete blood counts, liver function tests
- Mycophenolate mofetil:
- Indication: SLE, LN
- Drug Class: Immunosuppressive agent
- Dose: 500-1000 mg orally twice daily
- ADE: Gastrointestinal upset, bone marrow suppression, infections
- Monitoring: Regular complete blood counts, liver function tests
- Cyclophosphamide:
- Indication: SLE, LN
- Drug Class: Immunosuppressive agent
- Dose: Variable, depending on the patient's weight and disease severity
- ADE: Bone marrow suppression, infections, gastrointestinal upset
- Monitoring: Regular complete blood counts, liver function tests
- Calcineurin inhibitors:
- Indication: SLE, LN
- Drug Class: Immunosuppressive agent
- Dose: Variable, depending on the patient's weight and disease severity
- ADE: Nephrotoxicity, hypertension, gastrointestinal upset
- Monitoring: Regular kidney function tests, blood pressure monitoring
- Rituxan:
- Indication: SLE, LN
- Drug Class: Biologic agent
- Dose: 1000 mg intravenously every 2 weeks for 2 doses
- ADE: Infusion reactions, infections, gastrointestinal upset
- Monitoring: Regular complete blood counts, liver function tests
- Voclosporin:
- Indication: LN
- Drug Class: Immunosuppressive agent
- Dose: 23.7 mg orally twice daily
- ADE: Nephrotoxicity, hypertension, gastrointestinal upset
- Monitoring: Regular kidney function tests, blood pressure monitoring
- Hydroxychloroquine:
Supportive medications
- Glucocorticoids, such as prednisone, may be used to treat acute flares of SLE and LN 6, 3.
- Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat pain and inflammation associated with SLE and LN 3.
Other counseling points
- Patients with SLE and LN should be counseled on the importance of regular follow-up appointments with their healthcare provider to monitor their disease activity and adjust their treatment plan as needed 3.
- Patients should also be counseled on the potential side effects of their medications and the importance of reporting any changes in their symptoms or condition to their healthcare provider 3.