Yonatan Peleg, MD

Challenges in Integrating B-Cell Modulators into IgAN Clinical Practice

In this segment, the panel focuses on clarifying terminology and discussing evolving treatment strategies for IgA nephropathy. They agree that “supportive therapy” is a more accurate and appropriate term than “conservative therapy” when describing foundational management approaches. The discussion then turns to the potential of emerging treatments, particularly B-cell modulators, which offer the ability to more directly address the underlying pathophysiology of the disease. These therapies may reduce pathogenic GD-IgA1 production, lower hematuria and proteinuria, and help slow the decline in kidney function—key goals in IgA nephropathy management. The speakers contrast these newer mechanism-targeted options with traditional therapies like RAAS inhibitors and SGLT2 inhibitors, which provide benefit but do not directly modify the drivers of disease. Overall, the panel highlights that newer therapies represent an important advancement, offering opportunities to more effectively intervene in the biological processes central to IgA nephropathy.

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In this segment, the panel focuses on clarifying terminology and discussing evolving treatment strategies for IgA nephropathy.

Positioning Emerging B-Cell Modulators in Future IgAN Treatment Algorithms

In this segment, the panel discusses how B-cell modulators such as atacicept, sibeprenlimab, and povetacicept may fit within evolving treatment pathways for IgA nephropathy. They emphasize that optimized supportive care—including maximized RAAS inhibition, SGLT2 inhibitors, blood pressure control, and dietary sodium restriction—remains foundational. However, they note that persistent proteinuria despite these measures should prompt consideration of disease-modifying therapy. The panel explains that B-cell modulators may be positioned earlier in the treatment algorithm than traditional systemic corticosteroids because they target upstream pathogenic processes rather than broadly suppressing immunity. They also discuss differentiation among agents, including dosing schedules, biomarkers used to track response, and potential safety considerations. The discussion highlights that future treatment strategies may involve pairing supportive therapy with early initiation of a B-cell modulator, rather than reserving disease-modifying treatment only for advanced or rapidly progressive disease. Overall, the panel anticipates that these agents will shift practice toward earlier, mechanism-based intervention.

In this segment, the panel discusses how B-cell modulators such as atacicept, sibeprenlimab, and povetacicept may fit within evolving treatment pathways for IgA nephropathy.

In this segment, the panel discusses how monitoring strategies will need to adapt as B-cell–targeted therapies such as atacicept, sibeprenlimab, and povetacicept move into broader clinical use. They emphasize the importance of establishing a baseline immune profile, including serum IgG levels, vaccination history, and infection risk. During treatment, clinicians should monitor immunoglobulin levels periodically, watching for declines that may increase susceptibility to infection. The panel also notes that patients receiving B-cell modulators may require updated vaccination timing, ideally before therapy starts, since vaccine responses may be blunted once treatment begins. Routine kidney disease monitoring remains essential—tracking proteinuria, eGFR trends, and urine microscopy to evaluate therapeutic response. The group highlights the need for patient education, particularly around infection precaution behaviors and when to seek care. Overall, they stress that monitoring must be proactive and individualized, ensuring both safety and sustained disease control as these therapies enter practice.

In this segment, the panel discusses how monitoring strategies will need to adapt as B-cell–targeted therapies such as atacicept, sibeprenlimab, and povetacicept move into broader clinical use.

Monitoring Considerations with Emerging B-Cell Modulators in IgAN

Additional Emerging BAFF and APRIL Inhibitors in IgAN

In this segment, the panel reviews the emerging clinical data for two additional BAFF/APRIL–pathway inhibitors: sibeprenlimab and povetacicept. They first discuss sibeprenlimab, noting that phase 2 data demonstrated dose-dependent reductions in proteinuria along with sustained suppression of serum galactose-deficient IgA1 levels, supporting the mechanism of targeting upstream production of pathogenic IgA. The panel highlights that these effects were observed without broad immunosuppression, which may offer a favorable safety profile compared with systemic corticosteroids. The discussion then moves to povetacicept, which also targets BAFF and APRIL but with a slightly different binding and receptor engagement profile. Early trial data similarly show meaningful proteinuria reductions, and the panel emphasizes interest in how response durability and tolerability compare across molecules in this therapeutic class. They note that ongoing phase 3 and extension studies for both agents will be crucial for determining optimal patient selection, sequencing, and real-world adoption.

In this segment, the panel reviews the emerging clinical data for two additional BAFF/APRIL–pathway inhibitors: sibeprenlimab and povetacicept. 

Yonatan Peleg, MD

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