Safety of current treatments for paroxysmal nocturnal hemoglobinuria

Introduction: Eculizumab, which is indicated to treat patients with paroxysmal nocturnal hemoglobinuria (PNH), is proven to decrease intravascular hemolysis and thrombosis and improve survival. Ravulizumab is a long-acting, second-generation complement component 5 (C5) inhibitor designed to alleviate the burden of the eculizumab treatment schedule and reduce the frequency of breakthrough hemolysis. As the clinical benefits of these treatments have been emphasized, their safety also should be considered. Areas covered: This article reviews safety data for the current approved PNH treatments from published articles about eculizumab and ravulizumab in patients with PNH. Special settings (pregnancy, pediatrics, long-term safety of continued eculizumab treatment, and extravascular hemolysis) are also discussed. Expert opinion: In phase 3 trials, eculizumab and ravulizumab were found to be safe and well tolerated. In addition, 10 years of experience with eculizumab provided evidence that mitigates initial concerns about infectious events. However, to minimize meningococcal infections, vaccination and close monitoring remain essential. Because extravascular hemolysis limits eculizumab efficacy in some patients, continued investigation of proximal complement inhibitors is warranted to obviate this mechanism. Long-term safety data for ravulizumab treatment are needed.