From the Guidelines
Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can affect multiple organ systems, with lupus nephritis being a serious kidney manifestation occurring in approximately 40-60% of SLE patients, and the cornerstone of treatment is hydroxychloroquine at 200-400mg daily, with mycophenolate mofetil (MMF) as first-line for lupus nephritis at 2-3g daily divided doses, as recommended by the 2019 EULAR guidelines 1.
Epidemiology and Basic Pathophysiology
SLE predominantly affects women of childbearing age, with a female-to-male ratio of 9:1, and has higher prevalence among African Americans, Hispanics, and Asians. The pathophysiology involves production of autoantibodies, immune complex formation, complement activation, and subsequent tissue damage.
Risk Factors
Risk factors include female gender, genetic predisposition (HLA associations), hormonal factors, certain medications, UV light exposure, and infections.
Screening and Diagnosis
Screening typically involves ANA testing in patients with suggestive symptoms, while diagnosis requires meeting classification criteria including positive serologies (anti-dsDNA, anti-Smith), low complement levels, and clinical manifestations. For lupus nephritis specifically, kidney biopsy remains the gold standard for diagnosis and classification.
Treatment and Place of Therapy
Treatment begins with hydroxychloroquine as the cornerstone therapy for all SLE patients at 200-400mg daily, requiring baseline and periodic ophthalmologic exams to monitor for retinopathy.
- Hydroxychloroquine:
- Indication: All SLE patients
- Drug Class: Antimalarial
- Dose: 200-400mg daily
- ADE: Retinopathy
- Monitoring: Baseline and periodic ophthalmologic exams
- Mycophenolate Mofetil (MMF):
- Indication: Lupus nephritis
- Drug Class: Immunosuppressant
- Dose: 2-3g daily divided doses
- ADE: Cytopenias, diarrhea
- Monitoring: CBC and liver function
- Cyclophosphamide:
- Indication: Severe lupus nephritis
- Drug Class: Immunosuppressant
- Dose: 500-1000mg/m² monthly
- ADE: Cytopenias, hemorrhagic cystitis, infertility risk
- Monitoring: CBC, urine analysis
- Belimumab:
- Indication: SLE patients with inadequate response to standard therapy
- Drug Class: B-lymphocyte stimulator inhibitor
- Dose: 10mg/kg IV monthly or 200mg SC weekly
- ADE: Infections
- Monitoring: Infection monitoring
- Rituximab:
- Indication: Refractory lupus nephritis
- Drug Class: B-cell depleting agent
- Dose: 375mg/m² weekly for 4 weeks
- ADE: Infections
- Monitoring: Infection monitoring
Supportive Medications and Counseling Points
Supportive care includes corticosteroids for acute flares, antimalarials for skin manifestations, sunscreen use, vaccination planning, and bone health monitoring. Patient education should emphasize medication adherence, regular monitoring, and recognition of flare symptoms.
The 2019 EULAR guidelines recommend minimizing glucocorticoids to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawing them 1. The guidelines also recommend the use of immunomodulatory agents such as methotrexate, azathioprine, or mycophenolate to expedite the tapering or discontinuation of glucocorticoids.
In patients with persistently active or flaring extrarenal disease, add-on belimumab should be considered, while rituximab may be considered in organ-threatening, refractory disease 1.
The American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis recommend the use of mycophenolate mofetil or cyclophosphamide as initial treatment, with rituximab as an alternative for patients who fail to respond to initial therapy 1.
The KDIGO 2021 guideline for the management of glomerular diseases recommends the use of antimalarials in patients with SLE, and suggests a holistic approach to the management of lupus nephritis, including the use of glucocorticoids, immunosuppressants, and calcineurin inhibitors 1.
Overall, the management of SLE and lupus nephritis requires a comprehensive approach, including the use of immunosuppressants, glucocorticoids, and supportive care, as well as regular monitoring and patient education.
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
- Antinuclear antibody (ANA) test: A positive ANA test is often the first step in diagnosing SLE.
- Complete blood count (CBC): To check for anemia, low white blood cell count, or low platelet count.
- Urinalysis: To check for kidney damage or proteinuria.
Diagnosis
- American College of Rheumatology (ACR) criteria: A combination of clinical and laboratory criteria, including:
- Mucocutaneous manifestations (e.g., butterfly rash, discoid rash).
- Musculoskeletal manifestations (e.g., arthritis, myositis).
- Renal manifestations (e.g., proteinuria, hematuria).
- Neurological manifestations (e.g., seizures, psychosis).
- Hematological manifestations (e.g., anemia, leukopenia).
- Immunological manifestations (e.g., positive ANA, anti-dsDNA).
- SELENA-SLEDAI score: A measure of disease activity, including:
- Mucocutaneous manifestations.
- Musculoskeletal manifestations.
- Renal manifestations.
- Neurological manifestations.
- Hematological manifestations.
- Immunological manifestations.
Treatments and Place of Therapy
- Hydroxychloroquine: An antimalarial medication used to treat SLE, especially for mucocutaneous and musculoskeletal manifestations.
- Belimumab: A monoclonal antibody that targets BLyS, used to treat SLE, especially for patients with active disease and a history of severe flares.
- Mycophenolate mofetil: An immunosuppressive medication used to treat Lupus Nephritis.
- Cyclophosphamide: An immunosuppressive medication used to treat severe Lupus Nephritis.
- Calcineurin inhibitors: Medications used to treat Lupus Nephritis, especially for patients with severe disease.
- Rituxan: A monoclonal antibody that targets CD20, used to treat SLE, especially for patients with severe disease.
- Voclosporin: A calcineurin inhibitor used to treat Lupus Nephritis.
Belimumab
The proportion of patients achieving an SRI-4 response was significantly higher in patients receiving BENLYSTA plus standard therapy compared with placebo plus standard therapy. The trends comparing the treatment groups with respect to the probability of response for the individual components of the endpoint were consistent with that of the SRI-4 2
- Indication: Treatment of adult patients with active, autoantibody-positive SLE who are receiving standard therapy.
- Drug Class: Monoclonal antibody, BLyS inhibitor.
- Dose: 200 mg once weekly, administered subcutaneously.
- ADE: Infusion reactions, nausea, diarrhea, fever.
- Monitoring: Patients should be monitored for signs of infection, infusion reactions, and changes in laboratory parameters (e.g., complete blood count, liver function tests).
- Supportive medications: Patients may require supportive medications, such as antipyretics, antiemetics, and corticosteroids, to manage side effects.
- Other counseling points: Patients should be counseled on the importance of adhering to their treatment regimen, monitoring for side effects, and seeking medical attention if they experience any signs of infection or infusion reactions.
Mycophenolate Mofetil
- Indication: Treatment of Lupus Nephritis.
- Drug Class: Immunosuppressive medication.
- Dose: 1-2 grams twice daily, administered orally.
- ADE: Nausea, vomiting, diarrhea, leukopenia.
- Monitoring: Patients should be monitored for signs of infection, changes in laboratory parameters (e.g., complete blood count, liver function tests).
- Supportive medications: Patients may require supportive medications, such as antipyretics, antiemetics, and corticosteroids, to manage side effects.
- Other counseling points: Patients should be counseled on the importance of adhering to their treatment regimen, monitoring for side effects, and seeking medical attention if they experience any signs of infection.
Cyclophosphamide
- Indication: Treatment of severe Lupus Nephritis.
- Drug Class: Immunosuppressive medication.
- Dose: 500-1000 mg/m², administered intravenously.
- ADE: Nausea, vomiting, diarrhea, leukopenia, hemorrhagic cystitis.
- Monitoring: Patients should be monitored for signs of infection, changes in laboratory parameters (e.g., complete blood count, liver function tests).
- Supportive medications: Patients may require supportive medications, such as antipyretics, antiemetics, and corticosteroids, to manage side effects.
- Other counseling points: Patients should be counseled on the importance of adhering to their treatment regimen, monitoring for side effects, and seeking medical attention if they experience any signs of infection.
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 major cause of morbidity and mortality in patients with SLE, with approximately 40% of people with SLE developing LN, and an estimated 10% of people with LN developing end-stage kidney disease after 10 years 3.
Risk Factors
- The exact cause of SLE is unknown, but it is believed to involve a combination of genetic, environmental, and hormonal factors 3.
- Risk factors for developing SLE include being female, having a family history of SLE, and being of African American, Hispanic, or Asian descent 3.
Screening
- There are no universally accepted diagnostic criteria for SLE, but the 2019 European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) classification criteria are commonly used for scientific study 3.
- These classification criteria include both clinical factors, such as fever, cytopenia, rash, arthritis, and proteinuria, which may be indicative of lupus nephritis, as well as 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, low complement levels, and characteristic clinical features such as rash, arthritis, and proteinuria 3.
- Renal biopsy is indispensable for the management of LN, and can help to confirm the diagnosis and guide treatment decisions 4.
Treatments and Place of Therapy
- Hydroxychloroquine is standard of care for SLE and has been associated with a significant reduction in mortality 3.
- Other treatments for SLE include:
- Belimumab: a B cell targeting agent that has been approved for the treatment of SLE 3, 4, 5.
- Indication: active SLE, lupus nephritis
- Drug Class: biologic agent
- Dose: varies depending on the specific indication and patient population
- ADE: infusion reactions, infections, malignancy
- Monitoring: regular monitoring of disease activity, complete blood counts, and liver function tests
- Mycophenolate mofetil: an immunosuppressive agent that is commonly used to treat LN 3, 4, 6.
- Indication: lupus nephritis
- Drug Class: immunosuppressive agent
- Dose: varies depending on the specific indication and patient population
- ADE: gastrointestinal toxicity, hematologic toxicity, infections
- Monitoring: regular monitoring of disease activity, complete blood counts, and liver function tests
- Cyclophosphamide: an immunosuppressive agent that is commonly used to treat severe SLE and LN 3, 4, 6.
- Indication: severe SLE, lupus nephritis
- Drug Class: immunosuppressive agent
- Dose: varies depending on the specific indication and patient population
- ADE: gastrointestinal toxicity, hematologic toxicity, infections, infertility
- Monitoring: regular monitoring of disease activity, complete blood counts, and liver function tests
- Calcineurin inhibitors: a class of immunosuppressive agents that are commonly used to treat LN 6.
- Indication: lupus nephritis
- Drug Class: immunosuppressive agent
- Dose: varies depending on the specific indication and patient population
- ADE: nephrotoxicity, hypertension, hyperkalemia
- Monitoring: regular monitoring of disease activity, complete blood counts, and liver function tests
- Rituxan: a biologic agent that targets CD20-positive B cells and is used to treat refractory SLE and LN 7, 5.
- Indication: refractory SLE, lupus nephritis
- Drug Class: biologic agent
- Dose: varies depending on the specific indication and patient population
- ADE: infusion reactions, infections, malignancy
- Monitoring: regular monitoring of disease activity, complete blood counts, and liver function tests
- Voclosporin: a biologic agent that targets the calcineurin pathway and is used to treat LN 4.
- Indication: lupus nephritis
- Drug Class: biologic agent
- Dose: varies depending on the specific indication and patient population
- ADE: nephrotoxicity, hypertension, hyperkalemia
- Monitoring: regular monitoring of disease activity, complete blood counts, and liver function tests
- Belimumab: a B cell targeting agent that has been approved for the treatment of SLE 3, 4, 5.
Supportive Medications
- Glucocorticoids are commonly used to treat SLE and LN, but should be used at the lowest effective dose and for the shortest duration possible due to the risk of side effects 3, 7, 6.
- Other supportive medications may include:
- Antimalarials: such as hydroxychloroquine, which can help to reduce disease activity and prevent flares 3.
- Nonsteroidal anti-inflammatory drugs (NSAIDs): which can help to reduce pain and inflammation 3.
- Antihypertensive medications: which can help to control blood pressure and reduce the risk of cardiovascular disease 3.
Other Counseling Points
- Patients with SLE should be counseled on the importance of sun protection, as ultraviolet light can exacerbate disease activity 3.
- Patients with SLE should also be counseled on the importance of regular monitoring of disease activity, as well as the potential risks and benefits of treatment options 3, 4, 7, 6, 5.