When is iptacopan (Iptacopan) used in the treatment of IgA (Immunoglobulin A) nephropathy?

Iptacopan in IgA Nephropathy Treatment

Iptacopan is currently indicated for patients with IgA nephropathy who have persistent proteinuria despite maximal supportive care, as it targets the complement pathway involved in disease progression. 1

Current Treatment Approach for IgA Nephropathy

First-Line Management: Supportive Care

• The primary focus of IgA nephropathy management should be optimized supportive care 2
• Blood pressure control with ACEi or ARB therapy is recommended for all patients with proteinuria >0.5 g/day, regardless of hypertension status 2
• Lifestyle modifications including sodium restriction, smoking cessation, weight control, and regular exercise are essential components 2
• SGLT2 inhibitors should be considered for patients with persistent proteinuria or declining eGFR 2, 1
• Sparsentan is indicated for patients with persistent proteinuria 1

When to Consider Additional Therapy

• High risk of progression is defined as proteinuria >0.75-1 g/day despite at least 90 days of optimized supportive care 2
• Patients with persistent proteinuria should be considered for enrollment in clinical trials when available 2

Role of Iptacopan in IgA Nephropathy

Mechanism and Indication

• Iptacopan is a factor B inhibitor that targets the alternative complement pathway, which is activated in IgA nephropathy 1
• It has received conditional approval for IgA nephropathy treatment 1
• Iptacopan is part of the emerging therapies targeting complement inhibition in IgA nephropathy 2, 1

Patient Selection for Iptacopan

• Appropriate for patients who remain at high risk for progression despite maximal supportive care 1
• Should be considered in patients with:
  • Persistent proteinuria despite optimized RAS blockade 2, 1
  • Evidence of ongoing disease activity despite supportive measures 1

Treatment Algorithm for IgA Nephropathy Including Iptacopan

1. Initial Management:

   • Optimize supportive care with ACEi/ARB at maximally tolerated doses 2
   • Add SGLT2 inhibitor and/or sparsentan for persistent proteinuria 2, 1
   • Monitor proteinuria and eGFR for at least 90 days 2

2. If proteinuria persists >0.75-1 g/day despite supportive care:

   • Consider immunosuppressive therapy options 2
   • Evaluate for clinical trial eligibility 2
   • Consider targeted therapies including iptacopan 1

3. Specific scenarios where iptacopan may be particularly beneficial:

   • Patients with evidence of complement activation 1
   • Patients who cannot tolerate or have contraindications to glucocorticoid therapy 1
   • Patients with eGFR ≥30 mL/min/1.73m² who remain at high risk for progression 2, 1

Important Considerations and Caveats

• Iptacopan should not be used in variant forms of IgA nephropathy such as:

  • IgA deposition with minimal change disease 2
  • IgA nephropathy with acute kidney injury 2
  • Rapidly progressive IgA nephropathy with extensive crescents (>50% of glomeruli) 2

• Current treatment approach for high-risk patients may involve combining therapies:

  • Reduction of galactose-deficient IgA1 (using targeted-release budesonide)
  • Suppression of inflammation (using iptacopan) 1

• The optimal duration of iptacopan therapy remains uncertain and requires ongoing monitoring 1

• Patients with rapidly progressive IgA nephropathy should be treated with cyclophosphamide and glucocorticoids according to ANCA-associated vasculitis guidelines rather than iptacopan 2