Itepekimab and Brodalumab are two biologic medications being studied for asthma. Current biologics including Xolair, Nucala, Fasenra and Dupixent target downstream IgE, cytokines IL-5 and IL-4/13, have shown promising effects in terms of reduced asthma exacerbation rates, oral steroids, improved breathing capacity and asthma scores.
However approximately 30% of patients receiving biologics do not improve significantly. Instead of blocking downstream cytokines, targeting upstream alarmins, including IL-33, TSLP and IL-25, have been proposed to tackle the diverse causes of asthma.
We have discussed the above biologics in the past, here is a review of them below. We will discuss new ones on the horizon, Itepekimab and Brodalumab.
Itepekimab (Anti IL-33)
IL-33 is an inducer of Th2 adaptive immunity and signals via the IL-1 receptor-related protein ST2 triggering the release of chemokines and cytokines that promote T2 inflammation. Elevated levels of IL-33 mRNA produced by airway smooth muscle cells are detected from patients with asthma.
Itepekimab is an anti IL-33 monoclonal antibody, given subcutaneously 300mg every 2 weeks. Improvements in asthma control were statistically better than placebo.
Brodalumab (Anti IL-25)
IL-25 also known as IL-17E, is produced by bronchial epithelial cells and activates TH2 cells, basophils, eosinophils and mast cells, perpetuating T2 inflammation response in asthma. It has been shown IL-25 is associated with airway remodeling, which contributes to asthma severity.
In a phase 2 study, anti IL 17RA monoclonal antibody, brodalumab. Early studies did not show improvements in asthma control in patients with moderate to severe asthma. Further studies on the efficacy of anti-IL-25 blockade on other key outcomes will be needed.
Head to head biological asthma medications are unlikely in the near future. But picking the right one is crucially important by your asthma doctor. Blood eosinophil counts, total IgE and other comorbid conditions can help guide your doctor to pick the right one for you.