Clinical course and disease burden in patients with paroxysmal nocturnal hemoglobinuria by hemolytic status

https://doi.org/10.1016/j.bcmd.2017.03.013Get rights and content

Abstract

Disease characteristics of patients enrolled in the International PNH Registry were assessed during two follow-up periods based on hemolytic status while untreated with eculizumab: Non-hemolytic cohort: follow-up time defined as time from disease start until last reported untreated lactate dehydrogenase (LDH) value < 1.5 × upper limit normal (ULN); Hemolytic cohort: follow-up time defined as time from LDH ≥ 1.5 × ULN at or post-disease start, to most recent untreated follow-up. A total of 1012 patients met criteria for the Non-hemolytic cohort and 1565 patients for the Hemolytic cohort; median (min, max) years of follow-up were 2.2 (0.0, 54.2) and 1.2 (0.0, 37.2) years, respectively. Annual rate of thrombotic events (TEs) was lower in the Non-hemolytic than Hemolytic cohort (0.01 events/person-year vs. 0.03 events/person-year; p < 0.001). Mortality was lower in the Non-hemolytic cohort than the Hemolytic cohort (0.1% (1 death) vs. 1.8% (22 deaths); p < 0.001). While elevated risks for TEs were observed in patients with hemolysis, many TEs were also observed in patients without hemolysis. As thrombosis is the leading cause of mortality in patients with PNH, this real-world analysis highlights the importance of awareness and monitoring for TEs in patients with PNH regardless of hemolytic status.

Section snippets

List of abbreviations

AAaplastic anemia
BMDbone marrow disorder
CIconfidence interval
eGFRestimated glomerular filtration rate
LDHlactate dehydrogenase
MAVEMajor Adverse Vascular Event
PNHparoxysmal nocturnal hemoglobinuria
TEthrombotic event
ULNupper limit of normal
WBCwhite blood cell

Registry design and patients

The International PNH Registry is an ongoing prospective, multicenter, observational study, which has been described in detail elsewhere [8]. The Registry is sponsored by Alexion Pharmaceuticals, Inc., and is overseen by an independent committee of international medical PNH experts.

Patients of any age with a clinical diagnosis of PNH (by any applicable diagnostic method) or detectable PNH clone ≥ 0.01% are eligible for inclusion in the Registry. Data are collected at the time of enrollment and

Patient demographic and clinical characteristics

A total of 2386 patients of the 3550 patients enrolled in the PNH Registry as of April 8, 2015 were included in the analysis; 108 patients were excluded due to unknown eculizumab status or timing, or unknown date of disease start, while 1056 patients were excluded due to LDH values not reported between disease start and last untreated follow-up. Among the 2386 patients included in the current analysis, 821 patients had no reported hemolysis and 1374 patients had reported hemolysis; 191

Discussion

The International PNH Registry represents the largest worldwide, prospective, observational study of patients with PNH. This real-world analysis showed that PNH patients with hemolysis had increased PNH-related morbidity compared with PNH patients without hemolysis. With the exception of hemoglobin and eGFR values, patients with reported hemolysis in the Registry had different baseline laboratory values compared with patients with no reported hemolysis. Platelet counts at baseline differed

Conclusions

There is an increased risk of TE and MAVE in all patients with PNH, regardless of their hemolytic status; the risk is further elevated in patients with hemolysis. As thrombosis is the leading cause of mortality in patients with PNH, this real-world analysis highlights the importance of increased awareness and monitoring of TEs in patients with PNH, regardless of the presence of hemolysis. Similarly, although symptoms were more common in patients with hemolysis, a sizeable proportion of patients

Disclosures

PM has received speaker fees from Alexion Pharmaceuticals and served on advisory boards for Alexion Pharmaceuticals, Akari Therapeutics, and Ra Pharma. JS served on advisory boards for Alexion Pharmaceuticals and Ra Pharma and received lecture fees from Alexion Pharmaceuticals. MNY has served on advisory committees and speaker bureaus for Alexion Pharmaceuticals. AW is an employee of Alexion Pharmaceuticals and holds stock in the company.

Author contributions

MNY, PM, AW and JS contributed equally to the design of the study, interpretation of the data, writing of the manuscript, and approval of the final manuscript. AW contributed to the design of the study, statistical analysis, interpretation of data, writing of the manuscript, and approval of the final manuscript.

Funding sources

This work was supported by Alexion Pharmaceuticals.

Acknowledgements

Editorial support provided by Tmirah Haselkorn, Ph.D. of EpiMetrix, Inc. and funded by Alexion Pharmaceuticals.

References (12)

There are more references available in the full text version of this article.

Cited by (0)

View full text
© 2017 Elsevier Inc. All rights reserved.