Real life use of ravulizumab in Italian patients with paroxysmal nocturnal hemoglobinuria: evidence from the REACTION observational study

TL;DR

This study shows that ravulizumab is effective and well-tolerated in Italian patients with paroxysmal nocturnal hemoglobinuria, improving disease control and quality of life.

Contribution

The study provides real-world evidence of ravulizumab's effectiveness and safety in PNH patients previously treated with eculizumab.

Findings

92.3% of patients had LDH levels within or below 1.5 × ULN after 52 weeks of ravulizumab treatment.

Transfusion requirements decreased from 25.0% during eculizumab to 18.8% during ravulizumab.

Breakthrough hemolysis events were reduced during ravulizumab treatment compared to eculizumab.

Abstract

Ravulizumab is a second-generation C5i engineered from eculizumab to achieve immediate, complete, and sustained inhibition of terminal complement activity in PNH. The REACTION observational cohort study describes the effectiveness and tolerability of ravulizumab in Italian patients who were previously treated with eculizumab. Eighty-one PNH patients were enrolled in this study. The primary endpoint was the percentage change in lactate dehydrogenase (LDH) from baseline to the end of observation (52 weeks follow-up). Among secondary endpoints, transfusion avoidance, breakthrough hemolysis (BTH) and patients’ quality of life (QoL) were evaluated. The median (25–75 percentiles) percentage change in LDH at 52 weeks follow-up was -2.6 (-11.5–13.4) U/L, with 92.3% of the patients presenting LDH within or < 1.5 × upper limit of normal (ULN). Overall, 20 (25.0%) patients required transfusion during the eculizumab period and 15 (18.8%) during the ravulizumab. Seven BTH events were observed, 5 during eculizumab period and 2 (triggered by other medical conditions) during ravulizumab, suggesting the reduction of pharmacokinetic BTH during ravulizumab treatment. EORTC-QLQ-C30 and FACIT-Fatigue scores were similar to the general population, and patients’ preference indicated ravulizumab as the favorite treatment. The REACTION study confirmed the effectiveness of ravulizumab in maintaining stable disease and hemolysis control in the real-world setting. Clinical trial registration. NCT05274633, 02-Mar-2022.

The online version contains supplementary material available at 10.1007/s00277-026-06792-w.

Figures