Dual vs Single B-Cell Inhibition in IgAN: Duration and Safety Questions

In "Dual vs Single B-Cell Inhibition in IgAN: Duration and Safety Questions," the panel confronts what the trials have not yet answered.

Dr. Parikh asks Dr. Fervenza whether dual BAFF/APRIL inhibition offers benefit or added risk over APRIL inhibition alone. Dr. Fervenza reframes the discussion around a larger point. As of today, he says, there is no cure for IgA nephropathy. He compares it to ANCA vasculitis, a disease of remission and relapse, and warns some patients will relapse. He stresses trials gave drugs for a limited time and reached endpoints, but crucial questions remain. What clinicians do after nine months of treatment, whether to continue or stop, is unknown. He calls this an exciting but early moment, with much work ahead. Dr. Parikh shares his own worry about long-term immunoglobulin levels and the risk of hypogammaglobulinemia and infection. Dr. Mehdi notes galactose-deficient IgA levels rebound after stopping therapy, though the meaning is unclear. He explains BAFF acts early in B-cell maturation while APRIL acts later in class switching. He recalls that GWAS studies implicated APRIL and its receptor, not BAFF, yet efficacy appears comparable across agents so far. Dr. Rovin agrees that treating for nine months and stopping is unusual for immune-mediated kidney disease. He notes BAFF inhibition alone is extraordinarily safe, backed by two decades of lupus experience, but dual inhibition is less proven. He raises an intriguing possibility: longer treatment might allow a drug holiday once disease is quiet, with monitoring for flare as in lupus. Dr. Parikh closes on sequencing and shared decision making. He argues the real question is not which drug but what the patient needs and when, cautioning against overwhelming patients, insurers, and staff by starting everything at once.

In "Redefining Treatment Success in IgAN: Remission and Life Beyond Steroids," the panel turns to how the definition of treatment success is shifting toward disease modification and away from corticosteroids.