Introduction: Hemolysis Hemolysis: (hi-MOL-uh-suss) The destruction of red blood cells. in paroxysmal nocturnal hemoglobinuria paroxysmal nocturnal hemoglobinuria: (par-uk-SIZ-muhl nok-TURN-uhl hee-muh-gloe-buh-NYOOR-ee-uh) A rare and serious blood disease that causes red blood cells to break apart. Paroxysmal means sudden and irregular. Nocturnal means at night. Hemoglobinuria means hemoglobin in the urine. Hemoglobin is the red part of red blood cells. A… (PNH) is complement-mediated due to the lack of complement inhibitors in the hemopoietic cell membranes, making complement inhibition the best approach to manage PNH. Three complement inhibitors are approved by the European Medicines Agency as targeted therapy for PNH: eculizumab eculizumab: Eculizumab (Soliris ®) is given as an IV into a vein at the doctor’s office or at a special center. The procedure usually takes about 35 minutes. You will probably get an IV once a week for the first 4 weeks. Starting in the 5th week, you will get a slightly higher dose of Soliris every 2 weeks. … and ravulizumab, two humanized monoclonal antibodies targeting the same complement 5 (C5) epitope, approved in 2007 and 2019, respectively, and the more recently approved cyclic peptide, the complement 3 (C3) inhibitor pegcetacoplan pegcetacoplan: EMPAVELI® is the first PNH treatment that binds to complement protein C3. It was approved by the Food and Drug Administration in May 2021 for treating adult patients with paroxysmal nocturnal hemoglobinuria (PNH). EMPAVELI is given skin (subcutaneously) by using the Empaveli injector or with an… . Although national and international PNH treatment guidelines exist, they do not take into consideration the latest clinical trial clinical trial: A type of research study that tests how a drug, medical device, or treatment approach works in people. There are several types of clinical trials. Treatment trials test new treatment options. Diagnostic trials test new ways to diagnose a disease. Screening trials test the best way to detect a… evidence. Given the lack of evidence-based data for some clinical situations encountered in real life, we identified specific populations of patients who may benefit from switching to proximal C3 from terminal C5 inhibition.
Methods: The expert recommendations presented here were created using a Delphi-like process by a group of expert PNH specialists across Central Europe. Based on an initial advisory board meeting discussion, recommendations were prepared and reviewed as part of a Delphi survey to test agreement.
Results: Using a systematic approach, literature databases were searched for relevant studies, and 50 articles were reviewed by the experts and included as supporting evidence.
Conclusion: Implementation of these recommendations uniformly across healthcare institutions will promote the best use of complement inhibition in managing PNH, and has the potential to positively impact patient outcomes in Central Europe and worldwide.
Keywords: Complement C3; Complement C5; Complement inactivating agents; Hemolysis; Paroxysmal nocturnal hemoglobinuria.