U01.16.059 Anti-IL-5 Monoclonal Therapy

Introduction Anti-IL-5 monoclonal therapy is a targeted treatment that plays a crucial role in managing severe eosinophilic asthma. By inhibiting the actions of interleukin-5 (IL-5), this therapy prevents the differentiation, maturation, activation, and survival of eosinophils, which are key contributors to the inflammatory process in asthma.

Mechanism of Action

Inhibition of IL-5 Signaling

IL-5 Role: IL-5 is a cytokine that plays a central role in the growth, differentiation, recruitment, and activation of eosinophils.
Action of Anti-IL-5 Monoclonal Therapy: Anti-IL-5 monoclonal antibodies block the activity of IL-5, thereby reducing eosinophil levels and the associated inflammatory response.

Types of Anti-IL-5 Monoclonal Antibodies

Mepolizumab: Targets IL-5 directly, preventing it from binding to its receptor on eosinophils.
Reslizumab: Also targets IL-5, functioning similarly to mepolizumab in reducing eosinophil activity.
Benralizumab: Targets the IL-5 receptor α (IL-5Rα) on eosinophils, leading to their depletion through antibody-dependent cell-mediated cytotoxicity (ADCC).

Clinical Applications

Indications

Severe Eosinophilic Asthma: Anti-IL-5 monoclonal therapy is primarily used as maintenance therapy for patients with severe eosinophilic asthma who have not responded adequately to standard treatments.

Administration

Mepolizumab: Administered subcutaneously.
Reslizumab: Administered intravenously.
Benralizumab: Administered subcutaneously.

Drug	Target	Route of Administration
Mepolizumab	IL-5	Subcutaneous
Reslizumab	IL-5	Intravenous
Benralizumab	IL-5 receptor α	Subcutaneous

Points to Remember

Mechanism: Anti-IL-5 monoclonal therapy blocks IL-5 or its receptor, reducing eosinophil levels and the associated inflammation.
Indication: Used in severe eosinophilic asthma, particularly when standard treatments are ineffective.
Types: Mepolizumab and reslizumab target IL-5, while benralizumab targets IL-5Rα, leading to eosinophil depletion.

Bibliography

Ortega, H.G., et al. “Mepolizumab treatment in patients with severe eosinophilic asthma.” New England Journal of Medicine, 371.13 (2014): 1198-1207.
Castro, M., et al. “Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: Results from two multicenter, parallel, double-blind, randomized, placebo-controlled, phase 3 trials.” The Lancet Respiratory Medicine, 3.5 (2015): 355-366.
Bleecker, E.R., et al. “Benralizumab, an anti–interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (SIROCCO): a randomised, double-blind, placebo-controlled, phase 3 trial.” The Lancet, 388.10056 (2016): 2115-2127.

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