What are the treatment options for lupus?

Treatment Options for Systemic Lupus Erythematosus (SLE)

All patients with lupus should receive antimalarials (particularly hydroxychloroquine) as the cornerstone of therapy, unless contraindicated, with additional treatments tailored to disease severity and organ involvement. 1, 2

First-Line Treatment

• Hydroxychloroquine (HCQ) is indicated 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 2, 3
• Regular ophthalmological screening should be performed at baseline, after 5 years, and yearly thereafter to monitor for retinal toxicity 2
• Glucocorticoids (GCs) can be used for acute flares at doses depending on severity of organ involvement, with pulses of intravenous methylprednisolone providing immediate effect for severe flares 2
• For chronic maintenance treatment, GCs should be minimized to less than 7.5 mg/day and, when possible, withdrawn to prevent organ damage 1, 2
• Treatment should include photo-protection, osteoporosis prevention, cardiovascular risk management, metabolic syndrome monitoring, and infection prevention 1

Second-Line Treatment

• For patients not responding to HCQ alone or unable to reduce GC below acceptable doses, immunomodulating/immunosuppressive agents should be added 2, 4:
  • Methotrexate for skin and joint manifestations 2, 5
  • Azathioprine for maintenance therapy, particularly suitable for women contemplating pregnancy 2, 6
  • Mycophenolate mofetil for renal and non-renal manifestations (except neuropsychiatric disease) 2, 6
  • Cyclophosphamide for severe organ-threatening disease (especially renal, cardiopulmonary, or neuropsychiatric) 2

Organ-Specific Treatment Approaches

Lupus Nephritis

• Kidney biopsy is essential for diagnosis and treatment planning 2
• Induction therapy options include mycophenolate mofetil and cyclophosphamide 2, 6
• Low-dose cyclophosphamide is preferred over high-dose due to comparable efficacy and lower gonadotoxicity 2
• Maintenance therapy includes mycophenolate mofetil or azathioprine 2

Neuropsychiatric Lupus (NPSLE)

• Treatment depends on the underlying pathophysiological mechanism 2:
  • For inflammatory mechanisms: GCs and/or immunosuppressive agents 2
  • For embolic/thrombotic/ischemic mechanisms: anticoagulant/antithrombotic treatment 2
  • When both mechanisms coexist: combination of immunosuppressive and anticoagulant/antithrombotic therapy 2

Hematological Manifestations

• For significant thrombocytopenia: moderate/high doses of GCs in combination with immunosuppressive agents (azathioprine, mycophenolate mofetil, or cyclosporine) 2
• Initial therapy with pulses of IV methylprednisolone is recommended for severe manifestations 2
• For refractory cases: rituximab or cyclophosphamide 2

Biologic Therapies

• Belimumab is FDA-approved for active SLE and lupus nephritis in patients who have inadequate response to standard therapy 7, 6
• Rituximab may be considered for refractory cases, particularly for hematological manifestations 2, 4
• Anifrolumab is FDA-approved for active SLE 6, 8
• Voclosporin is FDA-approved specifically for lupus nephritis 6, 8

Common Pitfalls and Caveats

• NSAIDs should be used cautiously in SLE patients due to increased risk of renal, hepatic, and cutaneous adverse effects 9
• Lupus nephritis is a risk factor for NSAID-induced acute renal failure 9
• Hydroxychloroquine should be continued even during disease flares or when adding other medications, as it forms the basis of SLE treatment 10, 6
• Treatment goals should focus on achieving remission or low disease activity as soon as diagnosis is made and for as long as possible 1, 8
• Regular monitoring of disease activity using validated indices is crucial to adjust therapy appropriately 2
• Assess and minimize risk factors for comorbidities, including infections, atherosclerosis, hypertension, dyslipidemias, diabetes, osteoporosis, and malignancies 2