Ofatumumab for multirelapsing membranous nephropathy complicated by rituximab-induced serum-sickness

Rituximab (375mg/m(2)) achieved remission of the first episode and six relapses of nephrotic syndrome (NS) in a young male patient with podocyte phospholipase A(2) receptor (PLA(2)R)-related membranous nephropathy (MN) refractory to steroids and cyclosporine. Between-treatments interval averaged 17.4 +/- 4.2 months. The seventh infusion was complicated by delayed serum-sickness, which resolved with steroids. On subsequent relapse, the fully human anti-CD20 monoclonal antibody ofatumumab (300mg) achieved remission of the NS, without significant side effects. Circulating CD19(+) B cells were depleted, proteinuria decreased from 10.9 to 1.3g/day, and serum albumin, immunoglobulin levels and glomerular filtration rate normalised. Twenty-eightmonths later, despite transient anti-PLA(2)R depletion, ofatumumab (100mg) failed to induce remission of the eighth relapse. Remission was safely achieved 5months later with repeated ofatumumab infusion (300mg). This treatment (Euro723) was less expensive than rituximab (Euro1801). Ofatumumab could be a safe and cost/effective rescue therapy for patients with MN sensitised against rituximab.