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Successful management of unstable angina in a ravulizumab-treated patient with paroxysmal nocturnal hemoglobinuria.

ABSTRACT: Ravulizumab is an anti-C5 antibody approved for treating paroxysmal nocturnal hemoglobinuria (PNH). In August 2019, a 77-year-old Japanese man with PNH, who had been on ravulizumab treatment for 2 years, was hospitalized for chest discomfort and malaise. Electrocardiography identified a right bundle block, and elevated serum troponin I and d-dimer suggested ischemic heart disease. Cardiac catheterization revealed severe stenosis in the left anterior descending coronary artery, and intracoronary stenting relieved his chest discomfort. The final diagnosis was unstable angina unrelated to ravulizumab, and the patient's ravulizumab treatment was uninterrupted with no significant complications of PNH. This case report highlights the importance of continuing complement inhibition therapy during acute coronary events.

SUBMITTER: Takahashi H

PROVIDER: S-EPMC9840890 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Successful management of unstable angina in a ravulizumab-treated patient with paroxysmal nocturnal hemoglobinuria.

Takahashi Hiroshi H Mori Hirotaka H Fukatsu Masahiko M Sano Takahiro T Harada Kayo K Oikawa Masayoshi M Takeishi Yasuchika Y Kimura Satoshi S Ohkawara Hiroshi H Shichishima Tsutomu T Ikezoe Takayuki T

Fukushima journal of medical science 20220922 3

Ravulizumab is an anti-C5 antibody approved for treating paroxysmal nocturnal hemoglobinuria (PNH). In August 2019, a 77-year-old Japanese man with PNH, who had been on ravulizumab treatment for 2 years, was hospitalized for chest discomfort and malaise. Electrocardiography identified a right bundle block, and elevated serum troponin I and d-dimer suggested ischemic heart disease. Cardiac catheterization revealed severe stenosis in the left anterior descending coronary artery, and intracoronary ...[more]

PMID: 36130907

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Project description:IntroductionComplement factor 5 inhibitors eculizumab and, recently, ravulizumab are standard therapies for paroxysmal nocturnal hemoglobinuria (PNH). However, some patients experience suboptimal response and may benefit from dosage adjustments. Ravulizumab is administered less frequently than eculizumab on the basis of patient's body weight. This retrospective analysis of insurance claims investigated ravulizumab dosing patterns among patients with PNH from the USA.MethodsPatients aged ≥ 12 years with ≥ 2 ravulizumab infusions between June 21, 2019 and May 6, 2021, and ≥ 6 months of continuous clinical activity prior to first ravulizumab infusion (index date) were identified from the Symphony Health Integrated Dataverse (IDV®) database. Observed mean (standard deviation, SD) ravulizumab doses administered were reported and stratified by previous eculizumab use. Scenarios adjusting for patients' body weights (unavailable in Symphony Health IDV) based on the US general population distribution were performed to estimate percentages of patients receiving label-recommended doses.ResultsAmong 433 patients (mean [SD] age 47 [17] years), the mean (SD) loading dose was 3316.3 (2931.7) mg, greater than the maximal label-recommended loading dose (3000 mg for patients ≥ 100 kg). The mean (SD) loading doses were 3581.3 (3673.7) mg for eculizumab-naive versus 3093.1 (2096.8) mg for eculizumab-experienced patients. Over a mean (SD) treatment period of 11.8 (6.9) months, the mean (SD) average maintenance dose was 3403.7 (1024.4) mg, falling between label-recommended maintenance dose categories (3300 mg for ≥ 60 to < 100 kg; 3600 mg for ≥ 100 kg). Estimated percentages of patients receiving label-recommended loading and maintenance doses were 23.1% and 39.2%, respectively; 59.1% and 28.4% were estimated to receive above label-recommended loading and average maintenance doses, respectively.ConclusionAlthough limited by missing clinical characteristics including body weight, this study of ravulizumab dosing patterns in patients with PNH identified potential deviations from label-recommended dosing, warranting further investigations of treatment response to complement inhibitors in PNH.

Project description:Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder of hematopoietic stem cells genetically defined by the acquisition of somatic mutations in the X-linked phosphatidylinositol glycan anchor biosynthesis, class A (PIGA) gene. PIGA is essential for the synthesis of glycosyl phosphatidylinositol (GPI) anchor proteins and its mutations result in a deficiency of such molecules on the membrane of blood cells derived from the mutant clone. In particular, the lack of the GPI-linked complement regulatory proteins CD55 and CD59 is responsible for the increased sensitivity of PNH erythrocytes to complement-mediated destruction. Indeed, the classical clinical picture of PNH includes signs and symptoms of intravascular hemolysis along with variable degrees of cytopenia and a strong tendency to thrombosis, hallmarks of the disease. Before the introduction of anti-complement inhibitors, PNH was characterized by a high mortality primarily due to thrombotic events. The approval of the terminal anti-complement inhibitor eculizumab in 2007 introduced a paradigm shift in the treatment of the disease with improvement of the chronic hemolytic process and dramatic reduction of the thrombotic rate. However, eculizumab has a relatively short half-life when considering a life-long treatment, with obvious consequences as to the quality of life of treated patients necessitating relatively frequent drug administrations. Moreover, up to 30% of PNH patients undergoing eculizumab therapy show a suboptimal response, continuing to require red cell transfusions because of extravascular hemolysis or breakthrough hemolytic episodes. In 2019, the FDA approved the second-generation C5 inhibitor ravulizumab, a long-lasting agent with a better control of disease manifestations. Herein, we discuss the use of ravulizumab in PNH, its differences with first-generation C5 inhibitors, the research evidence supporting the safety and efficacy of this drug and its impact on costs for health systems and quality of life of PNH patients.

Dataset Information

Successful management of unstable angina in a ravulizumab-treated patient with paroxysmal nocturnal hemoglobinuria.

Publications

Successful management of unstable angina in a ravulizumab-treated patient with paroxysmal nocturnal hemoglobinuria.

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