Managing PNH

Untreated PNH can lead to early mortality.4 In fact, before the availability of today’s standard of care of C5 inhibitors, ~35% of patients died within 5 years.5,6

For this reason, rapid diagnosis of PNH and urgent initiation of a complement-mediated treatment that can block uncontrolled terminal complement activity – the cause of intravascular haemolysis (IVH), thrombosis and life-threatening consequences in PNH – is essential.1,7 

Breakthrough IVH is a return of IVH and its potentially life-threatening consequences due to inadequate complement inhibition, complement-activating conditions (triggers), such as an infection or surgery, or missed treatment dose.1,2,9 Complete and sustained terminal complement inhibition lowers the risk of breakthrough IVH events.1-3,11

Today, targeted C5 inhibition has transformed the natural history of PNH by improving the survival rate to near normal levels, similar to that seen in the general population.12,13

Disclaimer: Survival was not a prespecified endpoint, rather a post-hoc analysis and study was not powered to detect differences in survival. This study and OLE were not designed to assess survival. Death was a post-hoc safety endpoint. Survival analysis was performed using data for 192 complement inhibitor-experienced patients who received weight-based dosing of ravulizumab every 8 weeks for up to 4 years during the open-label extension phase of a Phase 3 randomized study (Study 302; ClinicalTrials.gov NCT03056040).

In PNH, residual anaemia can be due to several causes, thus it is important to confirm whether residual anaemia is due to EVH.14,15
Laboratory tests that are regularly used for monitoring PNH include (but are not limited to) high sensitivity flow cytometry, lactate dehydrogenase (LDH), reticulocyte count, complete blood count and serum bilirubin.20-23 It is recommended that high sensitivity flow cytometry is performed every six months for the first two years after diagnosis, and once a year thereafter.20
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Adverse Event Reporting

Please report any adverse events via your national reporting system. Adverse events can also be reported to Alexion, AstraZeneca Rare Disease by contacting: https://contactazmedical.astrazeneca.com/

Kulasekararaj AG, et al. The Importance of Terminal Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria. Therapeutic Advances in Hematology. 2022;13:20406207221091046. Lee JW, et al. Ravulizumab (ALXN1210) vs Eculizumab in Adult Patients with PNH Naive to Complement Inhibitors: the 301 study. Blood. 2019;133(6):530–539. Kulasekararaj AG, et al. Paroxysmal Nocturnal Hemoglobinuria. Blood. 2019;133(6):540–549. Brodsky RA. Paroxysmal Nocturnal Hemoglobinuria. Blood. 2014;18(124):2804–2811. Sharma VR. Paroxysmal Nocturnal Hemoglobinuria: Pathogenesis, Testing, and Diagnosis. Clinical Advances in Hematology & Oncology. 2013;9(11 Suppl 13):2–8. Hillmen P, et al. Natural History of Paroxysmal Nocturnal Hemoglobinuria. The New England Journal of Medicine. 1995;19(333):1253–1258. Lee JW, et al. The Role of the Alternative Pathway in Paroxysmal Nocturnal Hemoglobinuria and Emerging Treatments. Expert Review of Clinical Pharmacology. 2022;7(15):851–861. Hill A, et al. Paroxysmal Nocturnal Haemoglobinuria. Nature Reviews Disease Primers. 2017;(3):17028. Notaro R, Luzzatto L. Breakthrough Hemolysis in PNH with Proximal or Terminal Complement Inhibition. The New England Journal of Medicne. 2022;387(2):160–166. Kulasekararaj AG, et al. Ravulizumab Demonstrates Long-Term Efficacy, safety and Favorable Patient Survival in Patients with Paroxysmal Nocturnal Hemoglobinuria. Annals of Hematology. 2025; in press. ULTOMIRIS® EU Summary of Product Characteristics available at: https://www.ema.europa.eu/en/documents/product-information/ultomiris-epar-product-information_en.pdf. Last accessed March 2025. Kelly RJ, et al. Long-term Treatment with Eculizumab in Paroxysmal Nocturnal Hemoglobinuria: Sustained Efficacy and Improved Survival. Blood. 2011;117(25):6786–6792. Lee JW et al. Addition of Danicopan to Ravulizumab or Eculizumab in Patients with Paroxysmal Nocturnal Haemoglobinuria and Clinically Significant Extravascular Haemolysis (ALPHA): a Double-blind, Randomised, Phase 3 trial. The Lancet. 2023. Röth A, Duhrsen U. Treatment of Paroxysmal Nocturnal Hemoglobinuria in the Era of Eculizumab. European Journal of Haematology. 2011;87(6):473–479. Kulasekararaj AG, et al. Monitoring of Patients with Paroxysmal Nocturnal Hemoglobinuria on a Complement Inhibitor. American Journal of Hematology. 2021;7(96):E232–E235. [Medline Plus. Iron deficiency anemia. Available at: https://medlineplus.gov/ency/article/000584.htm. Accessed November 2023; Roth 2011; Kulasekararaj 2023]. Kulasekararaj AG, Lazana I. Paroxysmal Nocturnal Hemoglobinuria: Where Are We Going. American Journal of Hematology. 2023;98:S33–S43. DeZern AE, et al. Predictors of Hemoglobin Response to Eculizumab Therapy in Paroxysmal Nocturnal Hemoglobinuria. European Journal of Haematology. 2013;90:16–24; Alan E, et al. Overview of Hemolytic Anemia. Merck Manual. 2016. Kulasekararaj AG, et al. Biomarkers and Laboratory Assessments for Monitoring the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria: Differences Between Terminal and Proximal Complement Inhibition. Blood Reviews. 2023;59:101041.  Lima M. Laboratory Studies for Paroxysmal Nocturnal Hemoglobinuria, with Emphasis on Flow Cytometry. Practical Laboratory Medicine 2020;20:e00158.   Szlendak U, et al. Paroxysmal Nocturnal Hemoglobinuria: Advances in the Understanding of Pathophysiology, Diagnosis, and Treatment. Polish Archives of Internal Medicine. 2022;132:16271.   Sutherland R, et al. ICCS/ESCCA Consensus Guidelines to Detect GPI-deficient cells in Paroxysmal Nocturnal Hemoglobinuria (PNH) and Related Disorders Part 2- Reagent Selection and Assay Optimization of High-Sensitivity Testing. International Clinical Cytometry Society. 2017. Schrezenmeier H, et al. Baseline Clinical Characteristics and Disease Burden in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Updated Analysis from the International PNH Registry. Ann Hematol. 2020;99:1505-1514. Lee JW, et al. Clinical Signs and Symptoms Associated with Increased Risk for Thrombosis in Patients with Paroxysmal Nocturnal Hemoglobinuria from a Korean Registry. Int J Hematol. 2013;6(97):749–757.​ Jang 2024 et al. Impact of Lactate Drshydrogenase and Hemolglobin Levels on Clinical Outcomes in Patients with Paroxysmal Nocturnal Hemoglobinuria: Results from the National Korean PNH Registry. Journal of Korean Medical Science. 2024 1-10. advance I am a healthcare professional registered in the EU I am not a
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