Managing Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Patient-Focused Perspective

Abstract

The most frequently reported symptom in patients with paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by complement mediated hemolysis and chronic anemia, is “fatigue”. The latter seems the best word to communicate patient’ perception of personal health status and disease impact on daily living, namely quality of life (QoL). Objectivating QoL and grading patient’s fatigue is one of the most difficult medical tasks given the highly heterogeneous communication skills of patients and caregivers and the multitude of meanings that might be attributed to this term. Along with anemia, QoL in PNH is also affected by the emotional burden of a chronic life-long disease with heterogeneous treatment requirement, risk of hemolytic exacerbations (breakthrough hemolysis) and of thrombosis. In the last decade, structured surveys and scores have been adapted from cancer settings to evaluate fatigue and QoL in patients with PNH, and to assess the benefit of complement inhibitors in this setting. Eculizumab was the first drug utilized and was shown to improve QoL scores in the registrative trials. However, the intravenous fortnightly administration, the presence of residual anemia, and the risk of extravascular hemolysis are some of the unmet needs impacting QoL under eculizumab. Several novel drugs have been designed to improve patients’ convenience and alleviate anemia and fatigue. In this review, we focus on available studies that evaluated fatigue and QoL in PNH patients, and the effect of old and new therapeutic strategies.

Keywords:

• paroxysmal nocturnal hemoglobinuria
• novel drugs
• eculizumab
• quality of life
• fatigue

Data Sharing Statement

All data are available within the manuscript and further may be available upon reasonable request to the corresponding author.

Consent for Publication

All Authors approved present submission.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

Dr Bruno Fattizzo received consultancy honoraria and speaker bureau from Alexion, Amgegen, Annexon, Jannsen, and Novartis.

Dr Esther Natalie Oliva reports personal fees from Celgene, Janssen, personal fees, Daiichi, and Alexion, outside the submitted work.

Dr Wilma Barcellini received consultancy honoraria and speaker bureau from Agios, Alexion, Amgegen, Annexon, Jannsen, and Novartis.

Dr Francesca Cavallaro declares no conflicts of interest to disclose.

Additional information

Funding

No funding sources to declare.