Ravulizumab, a second-generation complement component 5 inhibitor (C5i) derived from eculizumab, with improved pharmacokinetics, is the current standard-of-care treatment for patients with paroxysmal nocturnal hemoglobinuria (PNH), where available. Pivotal trials have demonstrated durable long-term efficacy, safety, and improved survival, and increasing real-world evidence is required. This analysis utilized data from the International PNH Registry (NCT01374360) to evaluate the real-world effectiveness and safety of ravulizumab, and to assess baseline characteristics at treatment initiation. Adults (aged 18-65 years) enrolled in the registry as of July 1, 2024, who were treated with ravulizumab for ≥ 6 months were included and stratified by prior eculizumab use (eculizumab-experienced and C5i-naive). Ravulizumab treatment outcomes were assessed for up to 24 months and included change in lactate dehydrogenase (LDH) ratio from baseline, transfusion avoidance, and adverse event rates. Data for 203 eculizumab-experienced and 23 C5i-naive patients were analyzed. During treatment, LDH ratio was maintained near normal (< 1.5 × the upper limit of normal in both groups); 86.8% of eculizumab-experienced and 76.5% of C5i-naive patients were transfusion-independent, and a low rate of major adverse vascular events was reported (eculizumab-experienced, 0.4 per 100 person-years; C5i-naive, no events). These findings reinforce the pivotal trial outcomes and demonstrate the effectiveness and safety of ravulizumab in the real-world setting, further supporting ravulizumab as the first-line treatment of choice for patients with PNH, where available. Trial Registration: International PNH Registry: NCT01374360.
Röth et al. (2026) studied this question.