What is the recommended treatment for a patient with a positive Antinuclear Antibody (ANA) screen and elevated double-stranded Deoxyribonucleic Acid (dsDNA) antibody index?

From the Guidelines

The patient with a positive ANA screen and elevated dsDNA antibody index of 15.0 should be considered for immunosuppressive treatment, as these findings suggest active lupus nephritis (LN), which is associated with increased morbidity, mortality, and healthcare costs 1.

Key Considerations for Treatment

• The presence of a positive ANA screen and elevated dsDNA antibody index indicates a high likelihood of systemic lupus erythematosus (SLE) and potential kidney involvement, which necessitates a comprehensive treatment approach 1.
• According to the 2019 update of the joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations, immunosuppressive treatment is recommended in active class III or IV LN, with or without coexisting histological chronicity 1.
• For patients with pure class V LN, immunosuppression is recommended in cases with nephrotic-range proteinuria or proteinuria >1 g/24 hours despite optimal use of renin–angiotensin–aldosterone system blockers for a reasonable time period 1.
• The treatment should be tailored to the specific organ systems involved, disease severity, and patient characteristics, with regular monitoring of disease activity, medication side effects, and organ function being essential 1.

Treatment Options

• Hydroxychloroquine (HCQ) may be considered as part of the treatment regimen, given its benefits in reducing disease activity and preventing flares in SLE patients 1.
• Corticosteroids, such as prednisone, may be used to manage disease activity, especially in cases with significant organ involvement or severe symptoms 1.
• More potent immunosuppressants, such as mycophenolate mofetil, azathioprine, or cyclophosphamide, may be necessary for patients with severe or organ-threatening disease 1.

Monitoring and Follow-Up

• Regular assessment of disease activity, including laboratory tests (e.g., complete blood count, liver function tests, and urine analysis) and clinical evaluations, is crucial for adjusting the treatment plan as needed 1.
• Patients should be closely monitored for potential side effects of immunosuppressive medications and for signs of disease flare or progression 1.

From the FDA Drug Label

The primary efficacy endpoint was the SLE Responder Index-4 (SRI-4) at Week 52 as described in the intravenous trials Patients had to have a SELENA-SLEDAI score of ≥8 and positive autoantibody test (anti-nuclear antibody [ANA] and/or anti-double-stranded DNA [anti-dsDNA]) results at screening. 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.

The recommended treatment for a patient with a positive Antinuclear Antibody (ANA) screen and elevated double-stranded Deoxyribonucleic Acid (dsDNA) antibody index is BENLYSTA (belimumab) plus standard therapy, as it has been shown to significantly improve the SLE Responder Index-4 (SRI-4) response rate compared to placebo plus standard therapy 2.

• Key points:
  • BENLYSTA is administered via intravenous or subcutaneous routes
  • Patients should have a SELENA-SLEDAI score of ≥8 and positive autoantibody test results at screening
  • The treatment has been shown to reduce disease activity and improve SRI-4 response rate in patients with active SLE 2

From the Research

Treatment Overview

The patient's positive Antinuclear Antibody (ANA) screen and elevated double-stranded Deoxyribonucleic Acid (dsDNA) antibody index suggest a potential diagnosis of Systemic Lupus Erythematosus (SLE).

• The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications 3.
• Treatment goals include reducing disease exacerbations, hospitalizations, and organ damage due to the disease or treatment toxicity.

Recommended Treatment

• Hydroxychloroquine is standard of care for SLE and has been associated with a significant reduction in mortality 3, 4.
• In addition to hydroxychloroquine, immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, are typically used for treating moderate to severe disease 3.
• Biologic agents, such as belimumab, voclosporin, and anifrolumab, have been approved for the treatment of SLE and may be considered for patients with active disease 3, 4.
• The choice of treatment should be individualized based on the patient's specific disease characteristics, organ involvement, and response to previous treatments.

Disease Management

• Management of disease-related and treatment-related comorbidities, especially infections and atherosclerosis, is of paramount importance 5.
• New disease-modifying conventional and biologic agents-used alone, in combination or sequentially-have improved rates of achieving both short-term and long-term treatment goals, including minimisation of glucocorticoid use 5.
• For organ-threatening or life-threatening SLE, treatment usually includes an initial period of high-intensity immunosuppressive therapy to control disease activity, followed by a longer period of less intensive therapy to consolidate response and prevent relapses 5.