Personalizing C3G Treatment: Insights From Experienced Clinicians

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C3G Management Discussion

Background Therapy

• All C3G patients require nonimmunosuppressive background therapy:
• Renin-angiotensin-aldosterone system blockers (essential)
• SGLT2 inhibitors (recommended)
• Potential additions: glucagon-like peptide-1 agonists and mineralocorticoid receptor antagonists

Disease Progression

• Most C3G patients will progress despite conservative background therapy
• Management approaches have evolved significantly over the past 15 years

Traditional Immunosuppressive Approaches

• Various nonspecific immunosuppressive regimens have been tried
• Mycophenolate-based regimens with steroids (similar to lupus nephritis treatment) showed the most consistent benefit
• Most effective in patients with nephritic factors (60%-70% chance of significant proteinuria reduction)
• Limitation: Re-biopsies show continued accumulation of chronicity despite treatment

Limitations of B-Cell–Directed Therapies

• Despite C3G having autoimmune characteristics, B-cell–targeting agents have proven ineffective
• Possible explanations:
• Nephritic factors may not always be pathogenic
• Nephritic factors might only initiate the disease process, with complement dysregulation continuing independently afterward

New Era of Complement-Targeting Therapies

• First complement-targeting drug (Iptacopan) received FDA approval for C3G
• At least 1 other similar agent is expected to receive approval soon
• These targeted therapies address the underlying disease mechanism rather than just symptoms
• Even in patients with nephritic factors, complement-targeting therapy is now preferred over antibody-depleting approaches

Clinical Implications

• Treatment paradigm has shifted from nonspecific immunosuppression to targeted complement inhibition

Physicians should consider these newer options as they become available for C3G management