What treatment options are available for patients with systemic lupus erythematosus (SLE) who are unresponsive to conventional therapies such as corticosteroids, immunosuppressants, or antimalarials?

From the Guidelines

For patients with systemic lupus erythematosus (SLE) who don't respond to conventional therapies, biologics like belimumab and anifrolumab are recommended as add-on treatments, with belimumab administered at 10 mg/kg IV monthly or 200 mg subcutaneously weekly, as they have shown superiority to standard of care in high-quality randomised controlled trials 1.

Treatment Options

• Biologics:
  • Belimumab (Benlysta) targets B-lymphocyte stimulator protein and is FDA-approved specifically for SLE.
  • Anifrolumab (type I interferon receptor antagonist) has shown promise in treating SLE.
  • Voclosporin (calcineurin inhibitor) is approved for lupus nephritis.
• Immunomodulating/immunosuppressive agents:
  • Methotrexate, azathioprine, or mycophenolate can be used in patients not responding to conventional therapies 1.

Disease Severity and Organ Involvement

• Treatment selection should be guided by the specific organ systems affected and disease severity.
• For severe refractory cases, cyclophosphamide pulse therapy (500-1000 mg/m² monthly) may be considered, though it carries significant toxicity risks.
• Combination therapies using multiple mechanisms of action simultaneously often prove more effective than single agents.

Patient Characteristics and Monitoring

• Patient characteristics, including age, gender, and pregnancy status, should be considered when selecting treatments.
• Regular monitoring for medication efficacy and adverse effects is essential, with treatment adjustments made accordingly.
• The goal of treatment is to achieve remission or low disease activity, with the lowest possible dose of glucocorticoids, and prevent flares in all organs 1.

From the FDA Drug Label

The safety and effectiveness of BENLYSTA administered intravenously plus standard therapy were evaluated in 4 randomized, double‑blind, placebo‑controlled trials involving 2,581 adult patients with SLE 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. Effect on Concomitant Steroid Treatment: At baseline, 60% of patients were receiving prednisone at doses >7. 5 mg/day. Among these patients, 18% of patients receiving BENLYSTA plus standard therapy reduced their average prednisone dose by at least 25% to ≤7.5 mg/day during Weeks 40 through 52 Effect on Severe SLE Flares: The probability of experiencing a severe SLE flare, as measured by the modified SELENA-SLEDAI SLE Flare Index, excluding severe flares triggered only by an increase of the SELENA-SLEDAI score to >12, was calculated

Treatment Options for SLE:

• Biologics: Belimumab (BENLYSTA) is a biologic treatment option for patients with SLE who are unresponsive to conventional therapies.
• Key Benefits:
  • Reduces disease activity
  • Decreases the risk of severe SLE flares
  • Allows for reduction in concomitant steroid treatment
• Important Considerations:
  • Patients should have a history of autoantibodies (anti-nuclear antibody [ANA] and/or anti–double-stranded DNA [anti-dsDNA])
  • BENLYSTA is administered intravenously or subcutaneously plus standard therapy 2 2

From the Research

Treatment Options for Systemic Lupus Erythematosus (SLE)

• Systemic lupus erythematosus (SLE) is a chronic, autoimmune inflammatory disease with a multisystem manifestation and a variety of clinical symptoms 3.
• Conventional therapies for SLE include corticosteroids, immunosuppressants, and antimalarials, but these medications can have serious side effects and may not be effective for all patients 4, 5.

Biologics in SLE Treatment

• Biologic agents, such as belimumab and rituximab, have been recommended by the European Alliance of Associations for Rheumatology (EULAR) for the treatment of SLE 3, 4.
• Anifrolumab, an interferon (IFN) receptor inhibitor, and voclosporin, a novel calcineurin inhibitor, have also been added to the new SLE treatment guidelines 3.
• Other biologic agents targeting different cells or cytokines are being evaluated in phase II and III clinical trials 3.

Early Initiation of Belimumab

• Early initiation of belimumab, particularly within the first 5 years of diagnosis, may yield better outcomes by modulating disease progression and reducing flare frequency 6.
• Patients with shorter disease durations may achieve more substantial improvements in disease activity with early belimumab treatment 6.

Experimental Therapies

• Experimental therapies, such as targeting of plasma cells, chimeric antigen receptor T-cell therapy (CAR-T), or stem cell transplantation, appear promising in the treatment of severe forms of SLE 3.
• These therapies may offer new treatment options for patients with SLE who are unresponsive to conventional therapies or biologics.