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Pulmonary – Treatable traits
Published in Vibeke Backer, Peter G. Gibson, Ian D. Pavord, The Asthmas, 2023
Vibeke Backer, Peter G. Gibson, Ian D. Pavord
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.
Nasal Polyposis
Published in R James A England, Eamon Shamil, Rajeev Mathew, Manohar Bance, Pavol Surda, Jemy Jose, Omar Hilmi, Adam J Donne, 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
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Amanda Grippen Goddard, Harold S. Nelson, Rohit Katial, Flavia Hoyte
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).
Punctal stenosis associated with dupilumab therapy for atopic dermatitis
Published in Journal of Dermatological Treatment, 2021
Debora H. Lee, Liza M. Cohen, Michael K. Yoon, Jeremiah P. Tao
Given the relatively recent development of dupilumab, guidelines on management of its adverse effects have yet to be established. For dupilumab-induced conjunctivitis, initial management algorithms have proposed ophthalmology evaluation, ophthalmic preparations of antihistamines, corticosteroids, or immunosuppressive agents, and dupilumab taper or discontinuation (7). While no recommendations have yet been proposed for dupilumab-associated punctal stenosis, prior cases have described resolution with dupilumab discontinuation (though AD symptoms returned), as well as with a combination of corticosteroid eyedrops and reduction in dupilumab dosing frequency (6,7). In our cases, an assortment of strategies was elected, including discontinuation of dupilumab and treatment of conjunctivitis. For our third patient who preferred to continue dupilumab, we opted for a surgical alternative involving probing, punctoplasty, and silicone intubation. Other cases of spontaneous and medication-associated punctal stenosis and obstruction have been described, that have in some cases required Jones tube placement (i.e. direct puncture from caruncle to nasal cavity) if symptoms persisted despite other interventions (13).
Pharmacotherapeutic management of asthma in pregnancy and the effect of sex hormones
Published in Expert Opinion on Pharmacotherapy, 2021
Ruth P Cusack, Gail M Gauvreau
Dupilumab is a mAb that binds to the α subunit of the IL-4 receptor blocking signaling of both IL4 and IL-13 which are key cytokines in type 2 airway inflammation. Dupilumab has been approved by the FDA for the treatment of atopic dermatitis, and recently has been approved for the treatment of severe OCS dependent asthma. Animal studies of dupilumab in cynomolgus monkeys up to 10 times the maximal human dose found no fetal harm [98]. There has been a case report of dupilumab used safely in the treatment of atopic dermatitis in pregnancy [99]. The safety and efficacy of dupilumab in pregnant women are unknown as pregnancy was an exclusion criterion for all of the clinical trials. A review by the European Medicines Agency (EMA) in 2017 reported 23 pregnancies in study patients treated with dupilumab resulting in 8 healthy births (1 twin birth), 2 induced abortions, and 6 spontaneous abortions, with 2 of these 6 cases having at least one risk factor for abortion [100]. Five pregnancies were ongoing and three were lost to follow up. A pregnancy exposure registry for dupilumab is currently ongoing. EMA states that dupilumab should only be used during pregnancy if the potential benefits outweigh the potential fetal risks [101].
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.