{"type":"rich","version":"1.0","provider_name":"Transistor","provider_url":"https://transistor.fm","author_name":"GN in Ten","title":"Episode 12: NephMadness Special! IgAN (Again?!): New B-Cell Targets vs. Complement Inhibitors","html":"<iframe width=\"100%\" height=\"180\" frameborder=\"no\" scrolling=\"no\" seamless src=\"https://share.transistor.fm/e/b639cd5f\"></iframe>","width":"100%","height":180,"duration":1287,"description":"It’s the \"New England Journal of IgA\" these days, and we’re just living in it! In this special NephMadness edition of GN in Ten, hosts Dr. Kenar Jhaveri and Dr. Koyal Jain are joined by NephMadness co-creator Dr. Matt Sparks and Duke Fellow Dr. Ale Tomasi to break down the heavy hitters in the IgA Nephropathy bracket. Matt’s dog also joins us for a special, possibly biased cameo.We’re moving past \"ACE first, think later\" and diving into the upstream battle: B-cell modulators (BAFF/APRIL inhibitors) versus Complement inhibitors. Whether you’re team \"Hit Zero\" or team \"Alternative Pathway,\" this episode covers the latest trial data from ORIGIN, VISIONARY, and APPLAUSE to help you fill out your bracket. The \"Hit Zero\" HypothesisWhile we all know the classic four-hit hypothesis of IgAN, new therapies are targeting even further upstream—what some are calling \"Hit Zero.\" Pathophysiology Recap: IgAN starts with galactose-deficient IgA1 (Hit 1), leading to autoantibody production (Hit 2), immune complex formation (Hit 3), and mesangial deposition/damage (Hit 4). B-Cell Modulators: These drugs target BAFF (B-cell activating factor) and/or APRIL (a proliferation-inducing ligand) to reduce the production of those pesky autoantibodies right at the source. The B-Cell Contenders: Sibeprenlimab & AtaciceptSibeprenlimab (\"Sibi\"): A monoclonal antibody directed at APRIL. The Data: Showed a 50% reduction in proteinuria at interim analysis and a nearly 98% reduction in APRIL levels. Status: Currently has conditional FDA approval. Atacicept: A fusion protein that dual-blocks both BAFF and APRIL. The Data (ORIGIN trials): Demonstrated a 45.7% proteinuria reduction at 36 weeks and, notably, stabilization of eGFR slope in long-term follow-up. Pronunciation Debate: Is it \"Attack-a-cept\" or \"A-tassi-cept\"? The investigators say \"Attack,\" because it’s out for blood. The Complement Contender: IptacopanMechanism: A factor B inhibitor that specifically targets the alternative complement...","thumbnail_url":"https://img.transistorcdn.com/kA5i5pDNY48C1bT4aTakysX4M1kpvKsFppYIkQ0Hgfo/rs:fill:0:0:1/w:400/h:400/q:60/mb:500000/aHR0cHM6Ly9pbWct/dXBsb2FkLXByb2R1/Y3Rpb24udHJhbnNp/c3Rvci5mbS9zaG93/LzQ0NjQyLzE2OTM2/ODM5MzItYXJ0d29y/ay5qcGc.webp","thumbnail_width":300,"thumbnail_height":300}