Safety of current treatments for paroxysmal nocturnal hemoglobinuria

ABSTRACT

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.

KEYWORDS:

• Paroxysmal nocturnal hemoglobinuria
• eculizumab
• ravulizumab
• safety

Article highlights

• In phase 3 trials and real-world experience, eculizumab was found to be safe and well-tolerated.

• 10 years of experience with eculizumab provided evidence that mitigates initial concerns about infectious events.

• To minimize meningococcal infections, vaccination and close monitoring remain essential.

• Anemia and transfusion dependence persist due to extravascular hemolysis in some patients treated with C5 inhibitors.

• Long-term safety data for ravulizumab treatment are needed.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank eWorldEditing, Inc. (Eugene, OR, USA) for providing service of English editing under the auspice of manuscript supporting program by The Catholic University of Korea.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

JW Lee has received grants (to Seoul St. Mary’s Hospital) and honoraria from Alexion and served as a member of advisory board for Alexion, and served as a consultant for AlloVir. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.