Nasal Polyposis
R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne in Scott-Brown's Essential Otorhinolaryngology, 2022
Recent advances in biological treatments have resulted in availability of therapeutic monoclonal antibodies (mAbs) targeting several key mediators of NP pathogenesis that can potentially improve treatment of nasal polyposis in the setting of type 2 CRS: Omalizumab binds free circulating IgE, downregulates the expression of IgE receptors on mast cells/basophils and reduces release of inflammatory mediators ([IL-4).Dupilumab is an mAb to IL-4 receptor that inhibits the signaling of IL-4/IL-13 and reduces Th2-mediated inflammation. It is the only biological therapy approved for use in CRSwNP.Mepolizumab prevents activation of IL-5 receptors by binding to IL-5, which is important for differentiation/maturation/survival of eosinophils in tissue.
The Pharmacotherapy of Rhinitis and Asthma
Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial in Textbook of Allergy for the Clinician, 2021
Dupilumab is indicated for add-on maintenance treatment of patients with moderate to severe asthma with an eosinophilic phenotype or oral-corticosteroid dependent asthma. It is a fully human monoclonal antibody to the IL-4 receptor alpha subunit, a heterodimeric receptor complex for both IL-4 and IL-13. Blocking this receptor with dupilumab simultaneously inhibits IL-4 and IL-13 signaling. Dupilumab is effective by halting differentiation of CD4 positive lymphocytes, decreasing IgE production, decreasing fractional exhaled nitric oxide levels and decreasing airway hyper responsiveness and remodeling (Assaf and Hanania 2019). This drug should be used with caution in patients with extremely elevated baseline eosinophil counts due to the potential for a further rise in eosinophil counts (Katial et al. 2017).
Pulmonary – Treatable traits
Vibeke Backer, Peter G. Gibson, Ian D. Pavord in The Asthmas, 2023
Dupilumab is a monoclonal antibody targeting the IL-4 receptor-alpha, a common component of the IL-4 and IL-13 receptors. It, therefore, blocks the pathway leading to type-2 inflammation broadly by inhibiting the activity of both IL-4 and IL-13, whilst not affecting the inhibitory soluble IL-13 receptor. It is approved for use in atopic dermatitis, moderate-severe type-2 asthma and nasal polyposis and chronic rhinosinusitis. The large efficacy and broad effects on type-2 inflammation-related comorbidities such as nasal polyposis and atopic dermatitis make it an attractive treatment option for many patients. Efficacy against asthma attacks and the oral corticosteroid sparing effects are at least as good as is seen with anti-IL-5 biologics and the effect on asthma attacks is greater in patients with evidence of type-2 airway inflammation, particularly those with a raised FeNO. The effect of Dupilumab on FEV1 and symptom scores is greater than that seen with anti-IL-5 and anti-IgE biologics. A potential drawback is a requirement for 2-weekly dosing and an unclear safety profile in patients with blood eosinophil counts over 1.5 × 109/L. Tezepelumab has a similar range of clinical effects to Dupilumab although the effects on type-2 comorbid conditions has not been explored as extensively. As it acts proximally in the type-2 inflammatory pathway, all type-2 biomarkers are reduced by treatment.
Anti-IL-4/IL-13 for the treatment of asthma: the story so far
Published in Expert Opinion on Biological Therapy, 2020
For patients with steroid-dependent asthma, the LIBERTY ASTHMA VENTURE study provided solid evidence that dupilumab decreases severe asthma exacerbation rates despite OCS withdrawal. This makes dupilumab an attractive therapeutic option for this group of patients and suggests that, like mepolizumab and benralizumab, it has a more specific effect on T2 inflammation than systemic steroids and that there has likely been a degree of steroid resistance in these patients [82]. The ability to decrease or completely eliminate OCS use is hugely beneficial to both individual patients and population health and this has been a major achievement of these biological therapies. Patients taking chronic OCS are at greater risk of morbidity and a bigger focus on OCS-sparing treatments is needed in the modern era of asthma management [83].
Dupilumab for treatment of atopic dermatitis
Published in Expert Review of Clinical Pharmacology, 2018
Marlene Seegräber, Jerome Srour, Alexandra Walter, Macarena Knop, Andreas Wollenberg
The most common side effect of dupilumab is injection-site reactions, which mainly consist of transient erythema or edema. Conjunctivitis seems the only specific side effect [63]. The reason why dupilumab causes conjunctivitis is not fully understood and is currently being evaluated in ophthalmological sub-trials. Effects on vital functions were not observed. Dupilumab needs to be stored at 2–8°C, which may pose a disadvantage to some patients [44]. The product is stable at room temperature for up to 2 weeks, after taking it out of the refrigerator. The administration of live vaccines under treatment with dupilumab is currently not recommended according to the current label. This might be another disadvantage in case of intended travel or need of required booster shots.
Current and emerging pharmacotherapy for chronic spontaneous Urticaria: a focus on non-biological therapeutics
Published in Expert Opinion on Pharmacotherapy, 2021
Kam Lun Hon, Joyce T. S. Li, Alexander K.C. Leung, Vivian W. Y. Lee
CSU patients may have elevated serum IL-4 and/or IL-13 levels and increased expression of IL-4 mRNA [181]. Dupilumab is an anti-IL-4/IL-13 mAb which inhibits IL-4 Rα and reduces IL-4 and IL-13 cytokine-induced inflammatory responses, including the release of IgE [182–184]. Dupilumab is currently licensed for use in moderate-to-severe atopic dermatitis and as add-on maintenance treatment for asthma and chronic rhinosinusitis with nasal polyposis [185]. A phase III trial is investigating the efficacy of dupilumab in CSU patients with inadequate response to H1 antihistamine [186]. The results may suggest an alternative treatment option for omalizumab intolerant or incomplete responders.
Related Knowledge Centers
- Asthma
- Atopy
- Dermatitis
- Interleukin 13
- Interleukin 4
- Monoclonal Antibody
- Nasal Polyp
- Prurigo Nodularis
- Sinusitis
- Eosinophilic Esophagitis