Treatment Outcomes of Complement Protein C5 Inhibition in 509 UK Patients with Paroxysmal Nocturnal Hemoglobinuria

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic disorder which occurs on a background of bone marrow failure (BMF). In PNH, chronic intravascular hemolysis causes an increase in morbidity and mortality, mainly due to thromboses. Over the last 20 years treatment of PNH has focused on the complement protein C5 to prevent intravascular hemolysis using the monoclonal antibody eculizumab and more recently ravulizumab. In the UK, all patients are under review at one of two reference centers. We report on all 509 UK patients with PNH treated with eculizumab and ravulizumab between May 2002 and July 2022. The survival of patients with eculizumab and ravulizumab was significantly lower than age and sex matched controls (p=0.001). Only 4 patients died due to thromboses. The survival of patients with PNH (n=389) when those requiring treatment for BMF (clonal evolution to myelodysplastic syndrome or acute leukemia or had progressive unresponsive aplastic anemia (AA)) were excluded was not significantly different to age and sex matched controls (p=0.12). There were 11 cases of meningococcal sepsis (0.35 events per 100 patient years). Extravascular hemolysis was evident in patients treated, with 26.7% of patients requiring transfusions in the most recent 12 months on therapy. Eculizumab and ravulizumab are safe and effective therapies which reduce mortality and morbidity in PNH but further work is needed to reduce mortality in those with concomitant BMF.