What is the next step in therapy for a patient with active non-renal Systemic Lupus Erythematosus (SLE) already treated with prednisolone and hydroxychloroquine?

From the Guidelines

The next step in therapy for a patient with active non-renal Systemic Lupus Erythematosus (SLE) already treated with prednisolone and hydroxychloroquine is to consider adding an immunomodulatory agent such as methotrexate, azathioprine, or mycophenolate to expedite the tapering or discontinuation of glucocorticoids (GC) 1.

Key Considerations

• The goal of treatment is to achieve remission or low disease activity in all organ systems, with the lowest possible dose of GC 1.
• Hydroxychloroquine (HCQ) is recommended for all patients with SLE, at a dose not exceeding 5 mg/kg real body weight 1.
• Glucocorticoids (GC) should be minimized to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn 1.
• Immunomodulatory agents such as methotrexate, azathioprine, or mycophenolate can be added to expedite the tapering or discontinuation of GC 1.
• Belimumab may be considered in patients with inadequate response to standard-of-care, defined as residual disease activity not allowing tapering of GC and/or frequent relapses 1.
• Rituximab may be considered in organ-threatening disease refractory or with intolerance/contraindications to standard immunosuppressive agents 1.

Treatment Options

• Methotrexate: may be considered as an add-on therapy to HCQ and GC 1.
• Azathioprine: may be considered as an add-on therapy to HCQ and GC 1.
• Mycophenolate: may be considered as an add-on therapy to HCQ and GC 1.
• Belimumab: may be considered in patients with inadequate response to standard-of-care 1.
• Rituximab: may be considered in organ-threatening disease refractory or with intolerance/contraindications to standard immunosuppressive agents 1.

The FDA Drug Labels for prednisolone (PO), hydroxychloroquine (PO), azathioprine (PO), mycophenolate (PO), methotrexate (PO), etanercept (SQ) do not address this question.

From the Research

Next Steps in Therapy for Non-Renal SLE

The patient is already being treated with prednisolone and hydroxychloroquine. Considering the current treatment regimen, the next steps in therapy could be:

• Adding an immunosuppressant such as azathioprine or mycophenolate mofetil to reduce disease activity and steroid use 2, 3
• Using methotrexate as an alternative to azathioprine, as it has shown similar efficacy in reducing non-renal SLE activity 4, 5
• Considering the use of biologic agents such as belimumab, rituximab, or anifrolumab, which have shown beneficial effects in SLE management 6
• Continuing hydroxychloroquine as a long-term treatment, as it has been associated with improved survival and reduced disease activity 2, 3

Treatment Considerations

When selecting the next treatment step, consider the following:

• The patient's disease activity and organ involvement
• The potential side effects and risks associated with each treatment option
• The need to minimize steroid use and reduce the risk of long-term damage
• The importance of regular monitoring and follow-up to adjust treatment as needed 4, 5

Immunossuppressant Options

The following immunosuppressants have been studied in non-renal SLE:

• Azathioprine: associated with reduced mortality and improved survival 2
• Mycophenolate mofetil: effective in reducing disease activity and steroid use 3
• Methotrexate: shown to be effective in reducing non-renal SLE activity and flares 4, 5
• Cyclophosphamide: may be used in more severe cases, but its use is associated with cumulative damage and side effects 5