Dupilumab for treating severe asthma with type 2 inflammation

Dupilumab for treating severe asthma with type 2 inflammation

Dupilumab, a fully human monoclonal antibody, is directed against the alpha subunit of the IL-4 receptor, thereby blocking both IL-4 and IL-13 signaling, and hence type 2 inflammation

• immunologically, type 2 cytokines (specifically interleukin [IL]-4, IL-5, and IL-13) are recognized as playing a substantial pathobiological role in asthma
  • these cytokines link to a type-2/T-helper-2-cell (Th2)-high molecular asthma phenotype in up to 50% of asthmatic patients, across all levels of severity
  • pathophysiology of allergic asthma is mostly sustained by T-helper 2 (Th2) lymphocytes, which orchestrate and coordinate the immune inflammatory response of asthmatic airway (1)

NICE state (2):

• Dupilumab as add-on maintenance therapy is recommended as an option for treating severe asthma with type 2 inflammation that is inadequately controlled in people 12 years and over, despite maintenance therapy with high-dose inhaled corticosteroids and another maintenance treatment, only if:
  • the dosage used is 400 mg initially and then 200 mg subcutaneously every other week
  • the person has agreed to and follows an optimised standard treatment plan
  • the person has a blood eosinophil count of 150 cells per microlitre or more and fractional exhaled nitric oxide of 25 parts per billion or more, and has had at least 4 or more exacerbations in the previous 12 months
  • the person is not eligible for mepolizumab, reslizumab or benralizumab, or has asthma that has not responded adequately to these biological therapies
  • the company provides dupilumab according to the commercial arrangement

Evidence suggests that he effect of dupilumab on severe asthma in patients with atopic features could be started earlier than 2 weeks (3)

Australian guidance with respect to monoclonal antibodies (4):

• four monoclonal antibody therapies (benralizumab, mepolizumab, dupilumab and omalizumab) are available in Australia for the treatment of severe asthma in patients whose asthma is uncontrolled despite optimised standard treatment

Key Points

• monoclonal antibody therapy is an add-on treatment option for reducing severe flare-ups and improving symptom control in patients with severe allergic or eosinophilic asthma whose asthma is uncontrolled despite treatment with high-dose inhaled corticosteroids and long-acting beta2 agonists.
• these therapies target inflammatory pathways that activate type 2 immune responses leading to airway inflammation.
• patients using these treatments must keep taking their inhaled corticosteroid-containing preventers.
• after treatment has been initiated by a specialist, ongoing maintenance doses can be administered in primary care, or by the patient or carer, under specialist supervision.
• monoclonal antibody therapies currently available in Australia for severe asthma are generally well tolerated
  • injection site reactions are among the most common adverse events. Systemic reactions, including anaphylaxis, are rare but can occur.
• like all patients with asthma, those using monoclonal antibody therapies need an up-to-date written asthma action plan.

Notes:

• severe asthma is usually treated with inhaled corticosteroids plus another drug, such as a long-acting beta-agonist. Oral corticosteroids may also be needed to prevent exacerbations (asthma attacks), but they can cause long-term adverse effects. Also, these treatments may not work well enough for severe asthma with type 2 inflammation, which can be difficult to control
• clinical trial results show that adding dupilumab to standard asthma treatment is more effective than placebo plus standard treatment at reducing the frequency of severe exacerbations, and the use of oral corticosteroids in people with severe asthma with type 2 inflammation.

Reference:

• Vatrella A, Fabozzi I, Calabrese C, Maselli R, Pelaia G. Dupilumab: a novel treatment for asthma. J Asthma Allergy. 2014;7:123-130. Published 2014 Sep 4. doi:10.2147/JAA.S52387
• NICE (December 2021). Dupilumab for treating severe asthma with type 2 inflammation
• Tani, N., Kataoka, N., Kunimatsu, Y., Tachibana, Y., Sugimoto, T., Sato, I., Ogura, Y., Hirose, K., & Takeda, T. (2021). Early responders within seven days of dupilumab treatment for severe asthma evaluated by patient-reported outcome: a pilot study. Multidisciplinary Respiratory Medicine, 16. https://doi.org/10.4081/mrm.2021.736
• National Asthma Council - Australia. Monoclonal antibody therapy for severe asthma (accessed 24th November 2022).