How to manage Systemic Lupus Erythematosus (SLE)?

From the Guidelines

The management of Systemic Lupus Erythematosus (SLE) should prioritize hydroxychloroquine as the foundation of treatment, with a dose not exceeding 5 mg/kg real body weight, as recommended by the most recent and highest quality study 1.

Key Principles of SLE Management

• Begin with a thorough evaluation including complete blood count, comprehensive metabolic panel, urinalysis, complement levels (C3, C4), anti-dsDNA antibodies, and other relevant autoantibodies.
• For mild disease, hydroxychloroquine 200-400 mg daily is the cornerstone of treatment, reducing flares and organ damage.
• Add NSAIDs like naproxen 500 mg twice daily for joint pain and inflammation as needed.
• For moderate disease, incorporate corticosteroids such as prednisone 10-60 mg daily, with a plan to taper to the lowest effective dose, to quickly control inflammation.
• For severe or organ-threatening disease, consider immunosuppressants like mycophenolate mofetil 1-3 g daily, azathioprine 1-2.5 mg/kg/day, or cyclophosphamide per established protocols.
• For refractory cases, biologics such as belimumab or rituximab may be necessary, as suggested by 1.

Preventing Complications

• Assess and manage cardiovascular risk through dyslipidemia management, blood pressure control, and low-dose aspirin during pregnancy if necessary, as outlined in 1.
• Prevent proteinuria and CKD progression by avoiding high-sodium diets, optimizing blood pressure, using renoprotective medications, and preventing nephrotoxic insults and AKI.
• Reduce infection risk by assessing medical history, screening for HBV, HCV, HIV, and providing vaccinations and prophylaxis as needed.
• Protect bone health through calcium and vitamin D supplementation and bisphosphonates when appropriate.
• Limit ultraviolet light exposure and use broad-spectrum sunscreen.
• Consider gonadotropin-releasing hormone agonists for premature ovarian failure and evaluate individual risk factors for malignancies, minimizing lifetime cyclophosphamide exposure to <36 g, as recommended in 1.

Monitoring and Education

• Regular monitoring is essential, including clinical assessments every 1-3 months, laboratory tests to track disease activity and medication side effects, and screening for complications.
• Patient education about sun protection, adherence to medications, and recognizing flare symptoms is crucial for successful management. By following these guidelines and prioritizing the most recent and highest quality evidence 1, clinicians can provide effective management of SLE, reducing morbidity, mortality, and improving quality of life for patients.

From the FDA Drug Label

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 Effect on Concomitant Steroid Treatment: At baseline, 60% of patients were receiving prednisone at doses >7.5 mg/day. Among these patients, 18% of patients receiving BENLYSTA plus standard therapy reduced their average prednisone dose by at least 25% to ≤7.5 mg/day during Weeks 40 through 52 Effect on Severe SLE Flares: The probability of experiencing a severe SLE flare, as measured by the modified SELENA-SLEDAI SLE Flare Index, excluding severe flares triggered only by an increase of the SELENA-SLEDAI score to >12, was calculated

Management of Systemic Lupus Erythematosus (SLE):

• Belimumab administration: Belimumab can be administered intravenously or subcutaneously to manage SLE.
• Standard therapy: Belimumab should be used in combination with standard therapy, which may include corticosteroids, antimalarials, and immunosuppressives.
• Steroid reduction: Belimumab may allow for reduction in steroid dose, with 18% of patients receiving belimumab plus standard therapy reducing their average prednisone dose by at least 25% to ≤7.5 mg/day during Weeks 40 through 52.
• Severe SLE flares: Belimumab may reduce the probability of experiencing a severe SLE flare, as measured by the modified SELENA-SLEDAI SLE Flare Index.
• Response rate: The proportion of patients achieving an SRI-4 response was significantly higher in patients receiving belimumab plus standard therapy compared with placebo plus standard therapy 2.
• Lupus nephritis: Belimumab plus standard therapy may be effective in managing lupus nephritis, with a significantly higher proportion of patients achieving Primary Efficacy Renal Response (PERR) at Week 104 compared with placebo plus standard therapy 2.

From the Research

Overview of Systemic Lupus Erythematosus (SLE) Management

• Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that requires a comprehensive management approach 3.
• 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 3.

Pharmacologic Interventions

• Pharmacologic interventions for SLE are divided into four categories: antimalarials, glucocorticoids (GCs), immunosuppressants (ISs), and biological agents 4.
• Hydroxychloroquine is the most commonly used antimalarial treatment for SLE and is considered an anchor drug due to its multiple beneficial effects 4, 5.
• Glucocorticoids are used to decrease symptom severity, but their use is minimized due to adverse reactions 4.
• Immunosuppressants, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, are used to treat moderate to severe disease and to spare glucocorticoids 4, 6, 5, 3.
• Biological agents, such as belimumab, voclosporin, and anifrolumab, are used when other treatment options have failed due to intolerance or inefficacy 6, 3, 7.

Treatment Strategies

• Treatment strategies for SLE are individualized, and the choice of medication depends on the severity of the disease and the patient's response to treatment 3.
• The use of combination therapy, including antimalarials, immunosuppressants, and biological agents, may be necessary to achieve optimal disease control 4, 6, 5, 3.
• Corticosteroid sparing is an important goal in SLE management, and immunosuppressants and biological agents may be used to minimize glucocorticoid use 4, 7.

Emerging Treatments

• Emerging treatments for SLE focus on B and T cell downregulation and co-stimulation, cytokine inhibition, and immune vaccination 7.
• Several biologic agents, including rituximab and abatacept, have been investigated for the treatment of SLE, but their use is not yet widely established 7.
• Belimumab is the first biologic agent to have reached its primary endpoint in two randomized controlled trials for the treatment of SLE 7.