Clinical Report: Evaluating the Transition Between Complement Inhibitors in PNH

Overview

This study presents findings on the transition strategies between complement inhibitors in patients with paroxysmal nocturnal hemoglobinuria (PNH). The largest cohort to date was analyzed to establish consensus on managing treatment changes and avoiding breakthrough hemolysis.

Background

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease characterized by uncontrolled complement activation leading to severe anemia and other complications. The introduction of complement inhibitors has changed PNH management, yet guidance on switching between these therapies remains limited. Understanding the implications of treatment transitions is crucial for optimizing patient outcomes.

Data Highlights

Key Findings

• 65 patients were included from nine centers, with a median age of 40 years at PNH diagnosis.

• Indications for complement inhibition included hemolysis in 78% of patients.

• 149 changes in complement inhibitors were documented, with 75 being terminal-to-proximal transitions.

• Initial treatment responses varied, with 6 patients achieving complete response and 24 good response.

• Criteria for breakthrough hemolysis were defined based on lactate dehydrogenase levels.

Clinical Implications

Clinicians should be aware of the complexities involved in transitioning between complement inhibitors in PNH patients.

Conclusion

The findings from this study contribute to the understanding of treatment transitions in PNH.

Related Resources & Content

1. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria | New England Journal of Medicine

2. Drugs - Real World Outcomes, 2025 -- Outcomes and Management Strategies for Paroxysmal Nocturnal Hemoglobinuria Patients in China: Insights from a Real-World Study

3. Onkopedia, 2024 -- Paroxysmal Nocturnal Hemoglobinuria (PNH)

4. NICE, 2024 -- Iptacopan for treating paroxysmal nocturnal haemoglobinuria

5. PMC, 2024 -- Guidelines for the diagnosis and management of paroxysmal nocturnal hemoglobinuria

6. Open Forum Infectious Diseases — Should We Transition from Intermittent to Continuous Vancomycin Infusion?

7. Blood Cancer Journal — Real-World Insights on CPX-351 (Vyxeos™) for Treating Blast-Phase Myeloproliferative Neoplasms: A Study of 12 Consecutive Cases

8. Onkopedia Guidelines for PNH

9. NICE Technology Appraisal for Iptacopan

10. Guidelines for the diagnosis and management of paroxysmal nocturnal hemoglobinuria（2024） - PMC

11. Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria | New England Journal of Medicine

12. Pegcetacoplan versus eculizumab in patients with paroxysmal nocturnal haemoglobinuria (PEGASUS): 48-week follow-up of a randomised, open-label, phase 3, active-comparator, controlled trial - PubMed

13. Pegcetacoplan controls hemolysis in complement inhibitor–naive patients with paroxysmal nocturnal hemoglobinuria - PMC

14. Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria | New England Journal of Medicine

15. Oral iptacopan monotherapy in paroxysmal nocturnal haemoglobinuria: final 48-week results from the open-label, randomised, phase 3 APPLY-PNH trial in anti-C5-treated patients and the open-label, single-arm, phase 3 APPOINT-PNH trial in patients previously untreated with complement inhibitors - PubMed

16. Drug Trials Snapshot: FABHLATA | FDA

17. Drug Trials Snapshots: VOYDEYA | FDA

18. EMA/95105/2024

19. Drug Trials Snapshots: PIASKY | FDA

20. Phase 3 randomized COMMODORE 1 trial: Crovalimab versus eculizumab in complement inhibitor-experienced patients with paroxysmal nocturnal hemoglobinuria - PubMed

21. Full article: Expert consensus on the management of pharmacodynamic breakthrough-hemolysis in treated paroxysmal nocturnal hemoglobinuria

22. Managing transient immune complex reactions in patients with paroxysmal nocturnal hemoglobinuria: clinical observations from the COMMODORE 1 and 2 studies - PubMed

23. Mitigating Drug-Target-Drug Complexes in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Switch C5 Inhibitors - PubMed

24. Direct comparison of crovalimab versus eculizumab in paroxysmal nocturnalhemoglobinuria: A systematic review and meta-analysis of randomized controlled trials - ScienceDirect

25. Comparative efficacy of complement inhibitors in complement Inhibitor–Naïve PNH: A network meta-analysis of randomized trials - ScienceDirect