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Benralizumab: Cibler le récepteur de l’IL-5 dans l’asthme sévère éosinophile

Published Online:May 28, 2019https://doi.org/10.1024/1661-8157/a003250

Abstract

Zusammenfassung. Für Patienten mit schwierig kontrollierbarem, schwerem Asthma bronchiale stehen heute neben der inhalativen Medikation hochwirksame, gezielte Behandlungsmöglichkeiten zur Verfügung. Bei Vorliegen einer deutlichen Eosinophilie verspricht die Hemmung der Interleukin-5-Achse (IL-5) mit spezifischen, monoklonalen Antikörpern eine wirksame und nebenwirkungsarme Alternative zur dauerhaften systemischen Steroidtherapie. In diesem Übersichtsartikel werden die Daten zu Benralizumab, einem spezifischen Antikörper gegen den IL-5-Rezeptor Alpha, zusammengefasst. Dieser Angriffspunkt verhindert die Rezeptorstimulation durch IL-5 und aktiviert eine NK-zellvermittelte zytotoxische Reaktion, die zur Apoptose der eosinophilen Granulozyten führt. Die s.c.-Applikation von Benralizumab führt innerhalb von Tagen zur nahezu vollständigen Depletion der Eosinophilen im Blut mit konsekutiver Verbesserung der Lungenfunktion und Stabilisierung des Asthmas. Für ausgewählte Patienten mit schwerem Asthma eröffnet sich hier eine vielversprechende Therapie-Option.


Benralizumab: Targeting the IL-5 Receptor in Severe Eosinophilic Asthma

Abstract. Abstract:For patients with difficult-to-control, severe bronchial asthma, highly effective, targeted treatment options are available in addition to inhaled medication. In the presence of eosinophilia, inhibition of the interleukin-5 (IL-5) axis with specific monoclonal antibodies promises to be an effective alternative to continuous systemic steroid therapy with few side effects. This review summarizes the data on benralizumab, a specific antibody against the IL-5 receptor alpha preventing receptor stimulation by IL-5 and activating a NK-cell mediated cytotoxic reaction with apoptosis of eosinophils. The s.c.-application of benralizumab leads within days to a virtually complete depletion of blood eosinophils with consecutive improvement in lung function and stabilization of asthma. For selected severe asthmatics, this is a promising therapy option.


Résumé. Pour les patients asthmatiques sévères et difficiles à contrôler, il existe de nouvelles options thérapeutiques efficaces qui complémentent le traitement par inhalation. En cas d’éosinophilie périphérique, l’inhibition de l’axe interleukine-5 avec des anticorps monoclonaux spécifiques représente une alternative bien tolérée par rapport aux hautes doses prolongées de corticostéroïdes systémiques. Cette revue résume les données sur le benralizumab, un anticorps monoclonal contre le récepteur IL-5 alpha (IL-5R). Le benralizumab inhibe la stimulation du IL-5R et déclenche une réaction cytotoxique transmise par les les cellules NK, induisant une apoptose des éosinophiles. L’administration s.c. de benralizumab réduit fortement en espace de quelques jours les éosinophiles circulants avec amélioration de la fonction pulmonaire et stabilisation consécutive de l’asthme. Ce traitement représente une approche thérapeutique innovatrice pour des asthmatiques sévères sélectionnés.

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