J Korean Med Sci.  2023 Oct;38(41):e328. 10.3346/jkms.2023.38.e328.

Long-Term Efficacy and Safety of Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria and High Disease Burden: Real-World Data From Korea

• Kim JS
• Jang JH
• Jo DY
• Ahn SY
• Yoon SS
• Lee JH
• Kim SH
• Choi CW
• Shin HJ
• Kim MK
• Lee JH
• Mun YC
• Kong JH
• Hyun B
• Nam H
• Kim E
• Kwak MJ
• Won YK
• Lee JW

• KMID: 2547175
• DOI: http://doi.org/10.3346/jkms.2023.38.e328

Abstract

Background
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH.
Methods
This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009–2020 were enrolled.
Results
At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed.
Conclusion
These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens.

Keyword

Paroxysmal Nocturnal Hemoglobinuria; Eculizumab; Real-World Evidence; Overall Survival

Figure

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  Fig. 1 Rapid and sustained control of intravascular hemolysis by eculizumab, and the cumulative incidence of extravascular hemolysis and breakthrough hemolysis during eculizumab treatment. Changes in (A) LDH over time, (B) incidence and time to first occurrence of EVH, and (C) incidence and time to first occurrence of BTH.LDH = lactate dehydrogenase, EVH = extravascular hemolysis, BTH = breakthrough hemolysis, PY = patient-year, SD = standard deviation, ULN = upper limit of normal.aTwo patients were excluded for the following reasons: one patient who was pregnant with no complications at initiation of eculizumab and LDH (301 U/L) within the normal range (ULN = 480 U/L) at baseline; and one patient with LDH that was not collected at baseline.bOne patient had three BTH events.

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