INTRODUCTION: Hemolysis in paroxysmal nocturnal hemoglobinuria (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 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. Although national and international PNH treatment guidelines exist, they do not take into consideration the latest clinical trial 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.

Bone Marrow Transplant Unit Department of Hematology Emergency University Hospital Carol Davila University of Medicine and Pharmacy Bucharest Romania

Department of Hematology and Transfusion Medicine Jessenius Medical Faculty in Martin Comenius University in Bratislava Martin Slovakia

Department of Hematology and Transplantology Medical University of Gdansk Gdansk Poland

Department of Hematology Tokuda Hospital Sofia Sofia Bulgaria

Department of Hematology University Medical Centre Ljubljana Faculty of Medicine University of Ljubljana Ljubljana Slovenia

Department of Hemostasis Disorders and Internal Medicine Institute of Hematology and Transfusion Medicine Warsaw Poland

Department of Internal Medicine and Hematology Semmelweis University 46 Szentkirályi u Budapest 1088 Hungary

Department of Orphan Diseases National Research Medical Center for Hematology Moscow Russia

Division of Haematology Department of Internal Medicine University Hospital Center Zagreb School of Medicine University of Zagreb Zagreb Croatia

Institute of Hematology and Blood Transfusion Prague Czech Republic

RM Gorbacheva Research Institute Pavlov University St Petersburg Russia

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