Buchumschlag

Inhibition of Classical and Alternative Complement Pathway by Ravulizumab and Eculizumab

Objective To explore the feasibility of classical (CH50) and alternative (AH50) complement pathway activity as potential biomarkers for treatment guidance and monitoring during therapy with ravulizumab in patients with generalized myasthenia gravis (gMG) and compare these to therapeutic drug monitor...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Gerischer, Lea Morrin (VerfasserIn) , Stascheit, Frauke (VerfasserIn) , Mönch, Maximilian (VerfasserIn) , Doksani, Paolo (VerfasserIn) , Dusemund, Carla (VerfasserIn) , Herdick, Meret (VerfasserIn) , Mergenthaler, Philipp (VerfasserIn) , Stein, Maike (VerfasserIn) , Suboh, Amani (VerfasserIn) , Schröder-Braunstein, Jutta (VerfasserIn) , Wabnitz, Guido (VerfasserIn) , Lünemann, Jan D. (VerfasserIn) , Lehnerer, Sophie (VerfasserIn) , Hoffmann, Sarah (VerfasserIn) , Meisel, Andreas (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2025
In: Annals of Clinical and Translational Neurology
Year: 2025, Pages: ?
ISSN:2328-9503
DOI:10.1002/acn3.70251
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1002/acn3.70251
Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/acn3.70251
Volltext
Verfasserangaben:Lea Gerischer, Frauke Stascheit, Maximilian Mönch, Paolo Doksani, Carla Dusemund, Meret Herdick, Philipp Mergenthaler, Maike Stein, Amani Suboh, Jutta Schröder-Braunstein, Guido Wabnitz, Jan D. Lünemann, Sophie Lehnerer, Sarah Hoffmann, Andreas Meisel
Beschreibung
Zusammenfassung:Objective To explore the feasibility of classical (CH50) and alternative (AH50) complement pathway activity as potential biomarkers for treatment guidance and monitoring during therapy with ravulizumab in patients with generalized myasthenia gravis (gMG) and compare these to therapeutic drug monitoring under eculizumab. Methods In this prospective, exploratory real-world study CH50 and AH50, eculizumab and ravulizumab blood levels were assessed in patients with acetylcholine-receptor-antibody (AChR-ab) positive gMG. Patients were either pretreated with eculizumab or C5-inhibitor naïve. Samples were collected before the next infusion (end-of-dose). Laboratory data were correlated with patient-reported subjective duration of the ravulizumab effect. Results Overall, 61 patients were enrolled. At the end of their respective dosing interval, median AH50 levels were more strongly suppressed with eculizumab than with ravulizumab (1% [0%-2%] versus 5% [3%-9%]; Cohen's d 2.2 [95% CI 1.5-2.8]). Patients who discontinued ravulizumab due to insufficient effects (n = 19; 33%) had higher median AH50 levels than those who continued (7% [4%-13%] versus 5% [3%-8%]; Cohen's d −0.9 [95% CI −1.3 to −0.4]). In 81% (n = 46) of patients, the therapeutic effect of ravulizumab diminished before the subsequent infusion after the standard 8-week interval. Higher AH50 levels were correlated with earlier symptom recurrence. Interpretation Our results indicate potential differences in the ability of eculizumab and ravulizumab to suppress complement pathway activity through their respective dosing intervals. Additionally, higher AH50 levels might be a potential biomarker to predict poor therapy response and faster wearing off of ravulizumab's effect. However, these findings need to be validated in large multicenter studies.
Beschreibung:Gesehen am 17.03.2026
Beschreibung:Online Resource
ISSN:2328-9503
DOI:10.1002/acn3.70251

Ähnliche Einträge