What are alternative treatment options for a patient experiencing a lupus flare who cannot take steroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)?

From the Guidelines

For patients experiencing a lupus flare who cannot take steroids or NSAIDs, antimalarial medications like hydroxychloroquine (HCQ) at a dose not exceeding 5 mg/kg/real BW are recommended as a first-line treatment option. According to the 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus 1, HCQ is recommended for all patients with SLE, unless contraindicated. This recommendation is based on a high level of agreement among experts, with a mean score of 9.65 (1.11) out of 10.

Some key points to consider when treating a lupus flare without steroids or NSAIDs include:

• The use of immunosuppressive agents such as methotrexate, azathioprine, or mycophenolate mofetil, which can help control immune system overactivity 1.
• The consideration of biologics like belimumab for patients with inadequate response to standard-of-care treatments, defined as residual disease activity not allowing tapering of glucocorticoids and/or frequent relapses 1.
• The potential use of rituximab in organ-threatening disease refractory or with intolerance/contraindications to standard immunosuppressive agents 1.
• The importance of individualizing treatment based on the specific organs involved, severity of symptoms, and the patient's overall health status.

Non-pharmacological approaches, such as rest, stress reduction, avoiding sun exposure, and applying cold compresses to affected joints, can also complement medical treatment. These alternatives work by modulating different aspects of the immune response rather than broadly suppressing inflammation like steroids or NSAIDs do. As stated in the EULAR recommendations, treatment in SLE should aim at remission or low disease activity and prevention of flares in all organs, maintained with the lowest possible dose of glucocorticoids 1.

From the FDA Drug Label

The proportion of pediatric patients reporting at least one severe flare during the study was numerically lower in pediatric patients receiving BENLYSTA plus standard therapy (17%) compared with those receiving placebo plus standard therapy (35%) Pediatric patients receiving BENLYSTA 10 mg/kg plus standard therapy had a 64% lower risk of experiencing a severe flare during the 52 weeks of observation, relative to the placebo plus standard therapy group The proportion of patients achieving an SRI-4 response was significantly higher in patients receiving BENLYSTA plus standard therapy compared with placebo plus standard therapy.

Alternative treatment options for a patient experiencing a lupus flare who cannot take steroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) may include belimumab (IV or subcutaneous).

• Key benefits of belimumab include:
  • Reduced risk of severe SLE flares
  • Improved SLE responder index
  • Potential for reduced concomitant steroid treatment
• Clinical decision: Belimumab may be considered as an alternative treatment option for patients with lupus who cannot take steroids or NSAIDs, given its demonstrated efficacy in reducing severe flares and improving disease activity 2.

From the Research

Alternative Treatment Options for Lupus Flare

For patients experiencing a lupus flare who cannot take steroids or Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), several alternative treatment options are available:

• Azathioprine: This immunosuppressive drug has been shown to be effective in managing systemic lupus erythematosus (SLE) in patients who cannot take steroids or NSAIDs 3, 4.
• Hydroxychloroquine: This drug has been proven to be effective in reducing the risk of flares, allowing the reduction of steroid dosage, and preventing organ damage in SLE patients 5.
• Mycophenolate mofetil: This immunosuppressive drug has been demonstrated to be as efficacious as cyclophosphamide in patients with lupus nephritis 6.
• Belimumab: This anti-BLys antibody has been shown to be effective in reducing SLE activity and has been licensed for the treatment of SLE 6, 7.
• Epratuzumab: This humanized IgG1 monoclonal antibody targets CD22 and has been considered a potential treatment for SLE, although further research is needed to explore its efficacy 7.

Mechanisms of Action

These alternative treatment options work through various mechanisms, including:

• Immunosuppression: Azathioprine, mycophenolate mofetil, and cyclophosphamide work by suppressing the immune system to reduce inflammation and disease activity.
• B-cell modulation: Belimumab and epratuzumab work by targeting B-cells and reducing autoantibody production.
• Anti-inflammatory effects: Hydroxychloroquine has anti-inflammatory effects and can reduce the risk of flares and organ damage.

Safety and Efficacy

The safety and efficacy of these alternative treatment options have been studied in various clinical trials:

• Azathioprine has been shown to be effective and safe in SLE patients, with no increased risk of malignancies 3.
• Hydroxychloroquine is generally safe and can be prescribed to pregnant women, but caution is needed to prevent retinopathy 5.
• Belimumab has been licensed for the treatment of SLE and has been shown to be effective in reducing disease activity 6, 7.
• Epratuzumab has been considered a potential treatment for SLE, but further research is needed to explore its efficacy and safety 7.