Crovalimab Rescue Therapy in a Case With Genetic Complement Mediated Thrombotic Microangiopathy

Abstract Complement mediated thrombotic microangiopathy (C-TMA) is a rare disease resulting in kidney failure and other organ manifestations. Current treatments include the complement C5 blockers eculizumab and ravulizumab, as well as plasma therapy. We report on a young adult male with a long-standing history of genetic C-TMA (GC-TMA) due to a likely pathogenic missense variant in CFH. After several years without clinical signs of TMA and normal kidney function (CKD G1A2), without recent specific therapies, he presented with acute kidney injury, microangiopathic hemolysis, and nephrotic-range proteinuria. Plasma therapy and ravulizumab failed to stop hemolysis and he commenced kidney replacement therapy eleven days after admission. Laboratory analyses disclosed suboptimal complement inhibition and low free ravulizumab serum concentrations. Four weeks after admission we started treatment with crovalimab, a novel humanized anti-C5 antibody. Hemolysis improved immediately and kidney function recovered after three months of dialysis treatment and improved continuously during one year of therapy with crovalimab. The excellent and rapid response to crovalimab may suggest that the engineering of crovalimab, facilitating also subcutaneous administration, may result in a different pharmacokinetic and pharmacodynamic profile of crovalimab as compared to standard C5 inhibitors in patient with nephrotic range proteinuria.