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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\u2019 quality of life (QoL) were evaluated. The median (25\u201375 percentiles) percentage change in LDH at 52 weeks follow-up was\u2009-2.6 (-11.5\u201313.4) U\/L, with 92.3% of the patients presenting LDH within or &lt;\u20091.5 \u00d7 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\u2019 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. 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