Eculizumab Shows Long-Term Efficacy, Safety in PNH

Eculizumab demonstrated long-term safety and efficacy when used to treat paroxysmal nocturnal hemoglobinuria (PNH) in patients with high disease burdens, according to the Journal of Korean Medical Science. The treatment also mitigated complications and improved symptoms related to PNH.

PNH is a rare disorder that can lead to intravascular hemolysis, risk of thromboembolic events (TEs), and organ damage. Eculizumab has been approved for the treatment of patients with PNH, but previous studies on the effectiveness of PNH in Korean patients had excluded an assessment of treatment over time. This study aimed to evaluate long-term efficacy of eculizumab in patients who had high disease burden in PNH and severe complications of the disease.

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The retrospective, observational study enrolled patients who received eculizumab treatment for PNH from December 1, 2009, to January 31, 2020. Clinical information was collected from diagnosis to end of treatment or July 31, 2020. Data were collected before treatment, at 6, 12, and 24 months, and every 12 months after that. Patients who were aged 18 years and older who received treatment for PNH before January 31, 2020, were included. Patients were included if they had started eculizumab as part of a clinical trial or expanded access program.

Efficacy was evaluated using intravascular hemolysis, severity of anemia, and occurrence of PNH-related complications and symptoms. Investigator-assessed effectiveness was the primary endpoint of the study, and overall survival (OS) was another endpoint evaluated.

There were 80 patients enrolled with a median (range) age of 51.5 (18.0-88.0) years at time of starting eculizumab treatment and 62.5% identifying as male. The median length of time from diagnosis of PNH to treatment was 68.5 (2.0-456.0) months. A total of 75.0% of patients had classical PNH at diagnosis and 25.0% had aplastic anemia or myelodysplastic syndromes. Renal failure (36 patients), smooth muscle spasm (24 patients), TEs (20 patients), and pulmonary hypertension (15 patients) were the most reported symptoms that led to treatment. The median duration of treatment was 52.7 (1.0-127.3) months; 67.5% continued eculizumab treatment and 32.5% discontinued.

The mean (SD) change of LDH upper limit of normal (ULN) from baseline to the last follow-up was –6.5 (4.7)-fold. A total of 95.0% of patients achieved levels of LDH that were below 1.5 x ULN, and 61.3% achieved normal levels of LDH. Fatigue, anemia, and dyspnea incidences all decreased after starting eculizumab. A total of 14 of the 20 patients who reported TEs reported complete resolution while taking eculizumab; deep vein thrombosis was also resolved in all patients who had reported it. Patients who had reported smooth muscle spasm all reported being symptom-free after treatment, barring 1. Pulmonary hypertension resolved in 4 of 15 patients, and renal failure resolved in 16 of 36 patients.

The mean change of estimated glomerular filtration rate (eGFR) in patients with renal failure after using eculizumab was 28.6 (43.2) mL/minute/1.73 m², the mean change in eGFR in patients with chronic kidney disease was 6.4 (18.6) mL/minute/1.73 m², and the mean change was 57.1 (49.3) mL/minute/1.73 m² in patients with acute kidney injury. Hemoglobin also increased from a mean of 9.5 (1.7) g/dL at baseline to 10.4 (1.9) g/dL by the last follow-up. A total of 96.3% of patients were determined to have improved after treatment, with 1.3% remaining unchanged and 2.5% getting worse.

There were no patients who discontinued treatment due to any adverse events and no cases of infection that related to eculizumab were found. Although 2 deaths were reported after discontinuing eculizumab, neither was related to the treatment.

There were some limitations to this study. The retrospective nature could lead to confounding factors and cannot be used to establish causal relationships. There were many patients who discontinued the treatment due to being part of a clinical trial. The results may not be generalizable to patients outside of Korea. Symptoms of PNH were only assessed for 6 months prior to the start of treatment, which likely caused the miniscule differences in number of symptoms experienced before and after treatment.

The researchers concluded that eculizumab showed effectiveness in long-term treatment for patients with PNH who had high disease burden and severe complications related to PNH. Survivability was high during the study period and no adverse events led to the discontinuation of the treatment.

Reference

Kim JS, Jang JH, Jo DY, et al. Long-term efficacy and safety of eculizumab in patients with paroxysmal nocturnal hemoglobinuria and high disease burden: real-world data from Korea. J Korean Med Sci. 2023;38(41):e328. doi:10.3346/jkms.2023.38.e328