What is the treatment approach for Systemic Lupus Erythematosus (SLE)?

Treatment Approach for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine should be the cornerstone of therapy for all SLE patients, serving as the foundation upon which other treatments are added based on disease severity and organ involvement. 1

First-Line Treatment

• Hydroxychloroquine (HCQ) is recommended for all SLE patients at a dose not exceeding 5 mg/kg real body weight, as it reduces disease activity, prevents flares, and improves survival 1, 2
• Regular ophthalmological screening should be performed at baseline, after 5 years, and yearly thereafter to monitor for retinal toxicity 1
• Glucocorticoids (GC) can be used for acute flares, with pulses of intravenous methylprednisolone providing immediate therapeutic effect 3, 1
• For chronic maintenance treatment, GC should be minimized to less than 7.5 mg/day and, when possible, withdrawn to prevent organ damage 3, 1
• First-line treatment of skin disease includes topical agents (GC, calcineurin inhibitors), antimalarials (HCQ), and/or systemic GC 3

Second-Line Treatment

• In patients not responding to HCQ alone or in combination with GC, or unable to reduce GC below acceptable doses for chronic use, immunomodulating/immunosuppressive agents should be added 3, 1
• Methotrexate is effective for skin and joint manifestations 3, 1
• Azathioprine is suitable for maintenance therapy, particularly for women contemplating pregnancy 3, 1
• Mycophenolate mofetil (MMF) is effective for renal and non-renal manifestations (except neuropsychiatric disease) 3, 1
• Cyclophosphamide is reserved for severe organ-threatening disease or as "rescue" therapy in patients not responding to other immunosuppressive agents 3, 1

Biologic Therapies

• Belimumab should be considered in patients with inadequate response to standard therapy (combinations of HCQ and GC with or without immunosuppressive agents), defined as residual disease activity not allowing tapering of glucocorticoids and/or frequent relapses 3, 4
• Rituximab can be considered in organ-threatening disease refractory or with intolerance/contraindications to standard immunosuppressive agents 3, 1

Organ-Specific Treatment Approaches

Lupus Nephritis

• Early recognition of renal involvement and diagnostic renal biopsy are essential for optimal outcomes 3
• Mycophenolate or low-dose intravenous cyclophosphamide are recommended as initial (induction) treatment due to their favorable efficacy/toxicity ratio 3
• In high-risk patients (reduced GFR, fibrous crescents, fibrinoid necrosis, or tubular atrophy/interstitial fibrosis), high-dose intravenous cyclophosphamide can also be used 3
• For maintenance therapy, mycophenolate or azathioprine should be used 3
• In cases with incomplete renal response, mycophenolate may be combined with low-dose calcineurin inhibitors 3

Neuropsychiatric Lupus

• Distinguishing SLE-related from non-SLE-related neuropsychiatric manifestations is essential through neuroimaging, CSF investigation, and consideration of risk factors 3
• Treatment includes glucocorticoids/immunosuppressive agents for inflammatory manifestations and antiplatelet/anticoagulants for atherothrombotic/antiphospholipid antibody-related manifestations 3
• When both mechanisms coexist, combination of immunosuppressive and anticoagulant/antithrombotic therapy is recommended 1

Hematological Manifestations

• Acute treatment of lupus thrombocytopenia includes high-dose GC (including pulses of intravenous methylprednisolone) and/or intravenous immunoglobulin G 3
• For maintenance of response, immunosuppressive/GC-sparing agents such as mycophenolate, azathioprine, or cyclosporine can be used 3
• Refractory cases can be treated with rituximab or cyclophosphamide 3, 1

Monitoring and Prevention of Complications

• Regular assessment of disease activity using validated indices is crucial 1
• Monitor complement levels and anti-dsDNA antibodies to assess disease activity 1
• Screen for and minimize risk factors for comorbidities, including infections, atherosclerosis, hypertension, dyslipidemias, diabetes, osteoporosis, and malignancies 3, 1
• In patients with antiphospholipid antibodies, low-dose aspirin may be considered for primary prevention of thrombosis 1

Common Pitfalls and Caveats

• Hydroxychloroquine should not be discontinued during pregnancy or due to mild side effects, as it significantly reduces mortality 5
• Avoid prolonged use of high-dose glucocorticoids due to significant adverse effects; aim to taper to <7.5 mg/day as soon as possible 3, 1
• Cyclophosphamide should be used cautiously due to gonadotoxicity; consider fertility preservation measures before initiating therapy 1
• Regular monitoring for drug toxicities is essential, including ophthalmological screening for HCQ, bone density for glucocorticoids, and blood counts for immunosuppressants 1
• Treatment goals should focus on achieving remission or low disease activity and preventing flares in all organs 6