Efficacy and safety of obinutuzumab on progressive IgA nephropathy: a case series

IgA nephropathy (IgAN) is the most prevalent glomerulonephritis globally, significantly contributing to kidney failure. B cells are central to its pathogenesis through IgA production. While rituximab is commonly used to deplete B cells, obinutuzumab, a type II anti-CD20 antibody, may provide more effective and sustained depletion. This report regards the efficacy and safety of obinutuzumab in patients with progressive IgAN refractory to other immunosuppressive therapies. We discuss three patients with progressive IgAN aged 21, 35, and 57 years. All patients exhibited significant proteinuria and hematuria, with kidney biopsies confirming IgAN. In addition to supportive care, they all showed favorable responses to initial immunosuppressive therapy but developed kidney function impairment and nephrotic-range proteinuria 2-4 years after discontinuing initial treatments. Following intolerance and/or poor response to a new round of immunosuppressive medications, one patient was switched from rituximab to obinutuzumab (1000 mg), while 2 patients received obinutuzumab (1000 mg, 2 doses). After 12 months of follow-up, all patients achieved sustained B-cell depletion, with a reduction in IgA/C3, proteinuria, and hematuria, and improvement in kidney function. Mild infusion reactions were noted, but no severe adverse events occurred. These findings provide preliminary, hypothesis-generating insights into the efficacy of obinutuzumab in progressive IgAN and highlight the need for further studies on these issues.