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

Treatment Approach for Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine should be prescribed as the cornerstone of therapy for all patients with SLE unless contraindicated, serving as the foundation of treatment due to its ability to reduce disease activity, prevent flares, and improve survival. 1, 2

First-Line Treatment

• Hydroxychloroquine (HCQ) should be administered to all SLE patients at a dose not exceeding 5 mg/kg real body weight, with regular ophthalmological screening at baseline, after 5 years, and yearly thereafter 1, 2
• Glucocorticoids (GCs) should be prescribed at the lowest possible dose (≤7.5 mg/day prednisone equivalent) and for the shortest period of time to minimize adverse effects 3
• For acute flares, pulses of intravenous methylprednisolone can provide immediate therapeutic effect and enable lower starting doses of oral GCs 1
• Treatment goals should aim at remission or low disease activity and prevention of flares in all organs 3, 4

Second-Line Treatment

• In patients not responding to HCQ (alone or with GCs) or unable to reduce GCs below acceptable doses for chronic use, immunomodulating/immunosuppressive agents should be added 3
• For musculoskeletal manifestations, methotrexate (MTX), leflunomide (LFN), belimumab or abatacept can be considered, with cost and availability potentially favoring MTX 3
• For skin disease, first-line treatment includes topical agents (GCs, calcineurin inhibitors), antimalarials, and/or systemic GCs; for non-responsive cases, MTX, retinoids, dapsone, or mycophenolate can be added 3

Organ-Specific Treatment Approaches

Lupus Nephritis

• Early recognition of renal involvement and diagnostic renal biopsy are essential for optimal outcomes 3
• Mycophenolate mofetil (MMF) or low-dose intravenous cyclophosphamide (CYC) are recommended as initial (induction) treatment 3, 1
• For patients at high risk for renal failure, high-dose intravenous CYC can also be considered 3
• Maintenance therapy should include MMF or azathioprine (AZA) 3, 1
• In cases with incomplete renal response, mycophenolate may be combined with low-dose calcineurin inhibitors in the absence of uncontrolled hypertension, high chronicity index, or reduced GFR 3

Neuropsychiatric Lupus

• Treatment depends on the underlying pathophysiological mechanism 1
• For inflammatory manifestations, GCs and immunosuppressive agents are recommended 3, 1
• For atherothrombotic/antiphospholipid-related manifestations, antiplatelet/anticoagulant therapy is indicated 3, 1

Hematological Manifestations

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

Biological Therapies

• In patients with inadequate response to standard therapy (combinations of HCQ and GCs with or without immunosuppressive agents), belimumab should be considered 3, 4, 5
• Rituximab can be considered in organ-threatening disease refractory or with intolerance/contraindications to standard immunosuppressive agents 3, 5
• Anifrolumab, an interferon I receptor-targeting agent, has shown beneficial effects on SLE and is now FDA-approved for active SLE 4, 5

Monitoring and Prevention of Complications

• Regular monitoring of disease activity using validated indices is crucial 1, 6
• Assess and minimize risk factors for comorbidities, including infections, atherosclerosis, hypertension, dyslipidemias, diabetes, osteoporosis, and malignancies 1
• In patients with antiphospholipid antibodies, low-dose aspirin may be considered for primary prevention of thrombosis 1, 7

Common Pitfalls and Caveats

• Prolonged use of high-dose GCs increases risk of irreversible organ damage 3, 7
• Poor medication adherence, especially to HCQ, is associated with higher flare rates 7
• Regular assessment is essential to distinguish between pain due to active inflammation versus damage or fibromyalgia 7
• Despite advances in treatment options, access to newer biological therapies may be restricted in different regions of the world 6