Shifting the Treatment Paradigm of Severe Asthma With Novel Biologics - Episode 11
Geoffrey Chupp, MD, explains the key to future asthma treatment and the direction of the T2 paradigm.
Reynold Panettieri Jr, MD: JAK inhibitors are going to be interesting. Those are kinase inhibitors. Maybe they’ll have legs. Geoff, what do you think? Anything to add to Sid’s futuristic look?
Geoffrey Chupp, MD: The key to the future of asthma is to move away from the T2 paradigm. It’s not just about going to T2-low, but it’s really thinking more about the structural cells of the lung and the initiating events. We’re starting to move in that direction now, because we recognize that the current biologic therapies are doing pretty well at conquering the T2-high space. In that regard—you’re going to love this, Rey—the smooth muscle is not just an agent of airway caliber but of inflammation, which needs to be considered. The alarmin cytokine [IL-33] space is very interesting, of course, because we talk about how patients who have IL-5–driven disease and patients who have IL-13–driven disease. In the next few years, we may be talking about patients who have alarmin-driven disease and the adverse effects there, or maybe smooth muscle-driven disease. We’re using the downstream definitions now, based on sputum differentials for paucicellular, neutrophilic-driven asthma and things like that. Hopefully, we’re going to move toward more endotype-type definitions that are based on the targets for these other types of pathways that are driving the disease—both in people we see who are low-T2 and T2-high.
One last thing: Some of the other things have been used successfully in these patients—for example, macrolide therapy out of Australia—where there doesn’t appear to be a strong T2 signal, but whereas prospectively, they’ve shown improvements in the control of disease. Of course, the big unmet needs in the clinic are these patients who overlap, who have more than 1 disease in their lung, and we’re trying to figure out whether we create a new definition to call them—for example, ACOS [asthma-COPD overlap syndrome]—or do we start to recognize that they have more than 1 inflammatory process in their lung and we have to treat both of those things individually?
Reynold Panettieri Jr, MD: Geoff, I’m thrilled to hear that an immunologist had an epiphany that there are other cells that don’t migrate and that are important in the airways. This is wonderful as a smooth muscle biologist. But what you’re talking about is: Are we going to define asthmas different than T2-high, T2-low, smooth muscle endotype, epithelial cell endotype, and mast cell endotype? We already have hints of that with the omalizumab [Xolair] and IgE target. We’re evolving our thinking. There are going to be people who are more bronchodilator sensitive, but fragile and uncontrolled—which would really be a bronchomotor phenotype. I love the idea of redefining, with precision, what these individuals have, because in that precision comes targeted therapy. You hit the nail on the head. I really like that idea.
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Transcript Edited for Clarity