Low Rate of Clinically Evident Extravascular Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with a Complement C5 Inhibitor: Results from a Large, Multicenter, US Real-World Study

Abstract

Purpose Most patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with a complement protein 5 (C5) inhibitor achieve full control of terminal complement activity and intravascular hemolysis. The minority remains anemic and transfusion dependent despite this control. Etiology for ongoing anemia is multifactorial and includes bone marrow failure, breakthrough hemolysis, extravascular hemolysis (EVH) and nutritional deficiencies. Patients and Methods To evaluate the potential etiologies of hemoglobin levels <10 g/dL despite receiving C5 inhibitor therapy, we performed a retrospective US chart review of adult patients with PNH and treated for at least 12 months with eculizumab (n=53), ravulizumab (n=32), or eculizumab followed by ravulizumab (n=15). Clinically evident EVH was defined as at least one transfusion, reticulocyte count ≥120×10 9 /L and hemoglobin level ≤9.5 g/dL. Safety data were not collected. Mean treatment duration was 26.5±17.2 months. Results Treatment with C5 inhibitors significantly improved hemoglobin, lactate dehydrogenase, and number of transfusions versus baseline. Among the patients with hemoglobin <10 g/dL during the last 6 months of treatment (n=38), one patient (eculizumab) had clinically evident EVH, and 10 patients had active concomitant bone marrow failure. Bone marrow failure was a major contributor to hemoglobin <10 g/dL and transfusion dependence; clinically evident EVH was uncommon. Conclusion A range of hematologic causes need to be considered when evaluating anemia in the presence of treatment with a C5 inhibitor.

Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria (PNH): A Systematic Review and Expert Opinion from Central Europe on Special Patient Populations

“…Treat the triggering condition 11 (100) 2. Patients with clinically relevant C3-mediated EVH on C5 inhibitor treatment for ≥ 3 months 100.0% of patients treated with ECU show some degree of EVH [ 11 ] ∙ Consider a clinical trial if available ∙ Alternatively, switch to PGC d [ 12 , 87 , 90 ] 11 (100) 3. Patients with unprovoked TE while on C5 inhibitor for ≥ 3 months (a rare event) The rate of both venous and arterial TE during ECU treatment is 1.1 events per 100 PY [ 31 ] ∙ Consider a clinical trial if available ∙ Consider secondary thrombo-PPX with anticoagulants unless contraindicated [ 91 ] ∙ Alternatively, switch to PGC d and treat with anticoagulants; strongly consider switching if the TE event occurs on thrombo-PPX.…”