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

Treatment Approach for Systemic Lupus Erythematosus (SLE)

The treatment of SLE should aim for remission or low disease activity in all organs, maintained with the lowest possible dose of glucocorticoids, using hydroxychloroquine as the foundation of therapy for all patients unless contraindicated. 1

First-Line Treatment

• Hydroxychloroquine (HCQ) is recommended for all SLE patients at a dose not exceeding 5 mg/kg real body weight, serving as the cornerstone of therapy due to its ability to reduce disease activity, prevent flares, and improve 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 at doses and routes of administration that depend on the type and severity of organ involvement 1
• For acute flares, pulses of intravenous methylprednisolone (250-1000 mg per day, for 1-3 days) provide immediate therapeutic effect and enable the use of lower starting doses of oral GC 1
• For chronic maintenance treatment, GC should be minimized to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn to prevent organ damage 1

Second-Line Treatment

• In patients not responding to HCQ alone or in combination with GC, or in patients unable to reduce GC below acceptable doses for chronic use, immunomodulating/immunosuppressive agents should be added 1
• Options include:
  • Methotrexate (MTX) for skin and joint manifestations 1
  • Azathioprine (AZA) for maintenance therapy, particularly suitable for women contemplating pregnancy 1
  • Mycophenolate mofetil (MMF) for renal and non-renal manifestations (except neuropsychiatric disease) 1
  • Cyclophosphamide (CYC) for severe organ-threatening disease (especially renal, cardiopulmonary, or neuropsychiatric) 1

Organ-Specific Treatment Approaches

Lupus Nephritis

• Kidney biopsy is essential for diagnosis and treatment planning 1
• Induction therapy options:
  • MMF and CYC are the immunosuppressive agents of choice 1
  • Low-dose CYC (Euro-Lupus regimen) is preferred over high-dose CYC due to comparable efficacy and lower gonadotoxicity 1
• Maintenance therapy:
  • MMF or AZA are recommended for maintenance therapy 1

Neuropsychiatric Lupus (NPSLE)

• Treatment depends on the underlying pathophysiological mechanism 1:
  • For inflammatory mechanisms: GC and/or immunosuppressive agents 1
  • For embolic/thrombotic/ischemic mechanisms (with positive antiphospholipid antibodies): anticoagulant/antithrombotic treatment 1
  • When both mechanisms coexist: combination of immunosuppressive and anticoagulant/antithrombotic therapy 1

Hematological Manifestations

• For significant thrombocytopenia (platelet count <30,000/mm³):
  • First-line: moderate/high doses of GC in combination with immunosuppressive agents (AZA, MMF, or cyclosporine) 1, 3
  • Initial therapy with pulses of IV methylprednisolone (1-3 days) is recommended 3
  • IVIG may be considered in the acute phase or with inadequate response to GC 1
  • For refractory cases: rituximab or cyclophosphamide 1, 3
• Autoimmune hemolytic anemia (AIHA) follows similar treatment principles 1, 3

Biologic Therapies

• In patients with inadequate response to standard therapy, biologics should be considered 1:
  • Belimumab for active SLE and lupus nephritis 4
  • Anifrolumab for active SLE 4
  • Voclosporin for lupus nephritis 4
  • Rituximab may be considered for refractory cases, particularly for hematological manifestations 1, 3

Pain Management

• NSAIDs are recommended as first-line drug treatment for pain and stiffness, particularly for musculoskeletal manifestations 5
• For patients with increased gastrointestinal risk, consider either non-selective NSAIDs plus a gastroprotective agent or a selective COX-2 inhibitor 5
• Analgesics such as acetaminophen may be used when NSAIDs are insufficient, contraindicated, or poorly tolerated 5
• Local corticosteroid injections may benefit specific sites of musculoskeletal inflammation 5

Non-Pharmacological Approaches

• Patient education about the disease and pain management strategies is essential 5
• Regular exercise tailored to the patient's capabilities is recommended 5
• Physical therapy and psychological support for pain coping strategies should be incorporated 5

Monitoring and Prevention of Complications

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

Common Pitfalls to Avoid

• Prolonged use of high-dose glucocorticoids (>7.5 mg/day prednisone equivalent) increases the risk of irreversible organ damage 5
• Poor medication adherence, especially to hydroxychloroquine, is associated with higher flare rates 5
• Regular disease activity monitoring is essential to distinguish between pain due to active inflammation versus damage or fibromyalgia 5
• Mycophenolate mofetil, cyclophosphamide, and methotrexate should be avoided during pregnancy 6