Thrombotic Events in Patients With Paroxysmal Nocturnal Haemoglobinuria Using Eculizumab: A Post-Marketing...

Thrombotic events (TEs) account for approximately 40%-67% of deaths in untreated paroxysmal nocturnal haemoglobinuria (PNH). C5 inhibitor treatment (e.g., eculizumab and ravulizumab) greatly reduces the incidence of TEs in patients with PNH, but data on the characteristics of PNH patients experiencing TEs are limited.

This post-marketing surveillance sub-analysis evaluated the incidence of TEs in patients with PNH in Japan.

During eculizumab treatment, 54 TEs occurred in 44/794 patients (5.5%), an incidence of 1.50/100 patient-years. The most frequent TEs were deep vein thrombosis and cerebral infarction (eight events [14.8%]). A history of TE before eculizumab treatment was associated with TE during eculizumab treatment (p = 0.014), and greater cumulative incidences of TEs and multiple TEs during treatment (both p = 0.003) versus no history of TE. TEs were more frequent during the antithrombotic agent off-period (71.8%, 28/39) than during the on-period (28.2%, 11/39). TEs during eculizumab treatment were observed in patients with high lactate dehydrogenase (LDH) levels, infection events and longer administration intervals. Within the week before TE onset, LDH levels > 1.5 × the upper limit of normal were observed in 8/13 patients with TEs (61.5%), suggesting that intravascular haemolysis is not adequately suppressed in these patients.

Eculizumab helps prevent TEs in PNH. TE events appear to be associated with higher LDH levels, infections and long dosing intervals. Concurrent antithrombotic agent use to prevent TEs in PNH is likely clinically useful, especially in patients with a history of TE.

The authors have confirmed clinical trial registration is not needed for this submission.