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

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 man with a long-standing history of genetic C-TMA (GC-TMA) because of a likely pathogenic missense variant in <i>CFH</i>. 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 11 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 3 months of dialysis treatment and improved continuously during 1 year of therapy with crovalimab. The excellent and rapid response to crovalimab potentially suggests that the engineering of crovalimab, facilitating also subcutaneous administration, may result in a different pharmacokinetic and pharmacodynamic profile of crovalimab as compared with standard C5 inhibitors in patient with nephrotic range proteinuria.