Switching between complement inhibitors in paroxysmal nocturnal hemoglobinuria: Analysis of strategy, efficacy, and safety

HemaSphere, vol. 10, pp. e70427

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-orphan disease. In 2026, approved complement inhibitors (CIs) for PNH include three C5 inhibitors (C5i) and three proximal inhibitors (PIs). Clinical trials for the approved PI pegcetacoplan, iptacopan, and C5i + danicopan had clear protocols for changing from terminal to PI, extrapolated into real-world practice. There is no guidance for patients changing from a PI to a different CI. We present the largest international cohort to date. The inclusion criteria were as follows: patients established on a PI, who have changed treatment to a different CI. Sixty-five patients with a median age at PNH diagnosis of 40 years were included. Indications for CI switch were as follows: hemolysis (extravascular/recurrent breakthrough/not specified), side effects, trial termination, patient choice, and other. CI changes (149) were classified as (1) terminal-to-proximal (75/149), 6 hemolytic events reported within 14 days of CI change; (2) proximal-to-proximal (45/149), 2 hemolytic events reported within 14 days of CI change; and (3) proximal-to-terminal (29/149), 13 hemolytic events within 14 days of CI change. This is the largest cohort of PNH patients facing multiple CI changes. With the increasing availability of different CI classes, patients may experience several treatment changes over their disease course. CI should not be interrupted. The cohort would suggest that overlapping treatment for patients changing from PI to another CI is not required. Tapering of treatment does not seem to be effective at preventing hemolysis complications. Patients should be monitored closely for hemolysis, especially when changing from proximal-to-terminal inhibition. Prospective clinical/laboratory analysis is recommended for further clarification management for this patient group.

Authors 16

1. Morag Griffin corresponding

   St James's University Hospital

   Affiliation as printed

   Haematology Department St James University Hospital Leeds United Kingdom

2. Bruno Fattizzo

   University of Milan · Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

   Affiliation as printed

   Department of Oncology and Hemato‐Oncology University of Milan Milan Italy

   Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico Milan Italy

3. Jong Wook Lee

   Hanyang University Seoul Hospital

   Affiliation as printed

   Division of Hematology Oncology Hanyang University Seoul Hospital Seoul Republic of Korea

4. Richard J. Kelly

   St James's University Hospital

   Affiliation as printed

   Haematology Department St James University Hospital Leeds United Kingdom

5. Roochi Trikha

   King's College Hospital

   Affiliation as printed

   Department of Haematology Kings College Hospital London United Kingdom

6. Yasutaka Ueda

   The University of Osaka

   Affiliation as printed

   Department of Hematology and Oncology The University of Osaka Graduate School of Medicine Osaka Japan

7. Jun-Ichi Nishimura

   The University of Osaka

   Affiliation as printed

   Department of Hematology and Oncology The University of Osaka Graduate School of Medicine Osaka Japan

8. Christopher Jordan Patriquin

   University Health Network

   Affiliation as printed

   Division of Medical Oncology & Haematology University Health Network Toronto Ontario Canada

9. Alexander Röth

   Essen University Hospital · University of Duisburg-Essen

   Affiliation as printed

   Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen University Duisburg‐Essen Essen Germany

10. Petra Muus

    St James's University Hospital

    Affiliation as printed

    Haematology Department St James University Hospital Leeds United Kingdom

11. Jens Panse Aachen Department of Hematology, Oncology

    Universitätsklinikum Aachen · RWTH Aachen University

    Affiliation as printed

    Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD) Aachen Germany

    Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation University Hospital RWTH Aachen Germany

12. Miguel Gómez Álvarez

    Hospital Clínico San Carlos

    Affiliation as printed

    Facultativo especialista en Hematología y Hemoterapia Hospital Clinico San Carlos de Madrid Madrid Spain

13. Alexandra Pike

    St James's University Hospital

    Affiliation as printed

    Haematology Department St James University Hospital Leeds United Kingdom

14. Talha Munir

    St James's University Hospital

    Affiliation as printed

    Haematology Department St James University Hospital Leeds United Kingdom

15. Shreyans Gandhi

    King's College Hospital

    Affiliation as printed

    Department of Haematology Kings College Hospital London United Kingdom

16. Austin Gladston Kulasekararaj

    King's College London · King's College Hospital

    Affiliation as printed

    Department of Haematology Kings College Hospital London United Kingdom

    Kings College University Kings College London London United Kingdom