Shifting the Treatment Paradigm of Severe Asthma With Novel Biologics - Episode 10

Future of Asthma Treatment

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Reynold Panettieri, Jr, MD, and Sidney Braman, MD, discuss the future of asthma treatment for patients with non-allergic asthma or who may be ineligible for current biologic therapies.

Reynold Panettieri Jr, MD: How do I see the treatment of severe and persistent nonallergic asthma in the near future? I’m seeing at least 1 biologic on the horizon, and that 1 is focused on the anti-TSLP antibodies: tezepelumab, which is a really interesting drug. We’re going to discuss that, but I’d also be happy to hear what my colleagues think. We’ve had some refinement in the use of bronchial thermoplasty— studies showing that 1 is as good as 3 if you have focused therapeutic approaches. But the Achilles’ heel for severe asthma management is the low T2 space. We haven’t made any progress. We know macrolides might work, and we’ve talked about—just momentarily—bronchial thermoplasty, but beyond that, there’s a huge unmet need. Of the comorbidities that Nic talked about, the obesity phenotype is really quite unique. Maybe anti–IL-6s will be tried there. There are ongoing trials for PrecISE, which is the severe asthma network funded by NHLBI [National Heart, Lung, and Blood Institute]. But right now, in this space, what are we using? We’re using macrolides on Monday, Wednesday, and Friday as an adjuvant. It’s not used as an anti-infective but as a potential anti-neutrophil drug. We also have bronchial thermoplasty, as I’ve mentioned. Sid, why don’t you take the first question: What treatment options may be available for patients who are ineligible for biologics? What have you used? I want you to put on your glasses to see into the future.

Sidney Braman, MD: That’s tough. What we’re doing is if they’re not responding to corticosteroids, tapering is something that should be done slowly; this has been recommended. Certainly, ask them about smoking, for example. Smoking cessation would be a very important part of this, as Nic mentioned earlier. Avoidance of any of the potential environmental factors they may have—like where they’re working—would be something that you’d think about. I would make sure that they’re at least on a LAMA [long-acting muscarinic antagonist]–LABA [long-acting beta-agonist] for bronchodilation. Some have suggested attempting roflumilast, the drug that’s approved for COPD [chronic obstructive pulmonary disease]. It doesn’t have the indication in asthma, but many of these patients have a persistent airflow obstruction, and there’s evidence that it may actually have some biologic aspects for asthma. Maybe low-dose theophylline would be another drug that would be attempted and treated—to see if it could be improved.

One of the things that all the guidelines say is that some of the immunosuppressive agents—like methotrexate, which we used 100 years ago—are no longer worthwhile. Lastly, and most importantly—this has been brought up several times during the discussion: obesity in asthma. You mentioned that it’s a fascinating thing. Now, this wasn’t known until the late 1990s, when the Nurses’ Health Study came out and said, “It looks like our obese nurses have twice the rate of asthma as those who do not have obesity.” I don’t think a lot of people believed this until future studies clearly proved this relationship.

Two of the things we know about this group of non-T2 asthmatics is that the asthma was really more neutrophilic driven, IL-6 perhaps, and that weight loss can be very effective or can improve symptoms. I saw a patient years ago who had bariatric surgery, so weight loss but also asthma pretty much went away with very minimal adverse effects. I saw a fascinating article awhile back on the use of pioglitazone, which has an effect on leptin and adiponectin, which are reversed in obese individuals. Leptin, as we know, is very pro-inflammatory and actually causes airway hyperresponsiveness in experimental animals. There are a lot of things in that realm. 

You mentioned the anti-IL-6s in the future, and certainly, some of the attention goes to the tyrosine kinase inhibitors: masitinib and imatinib. These are things that will probably be trialed in the future, and we may have some positive results. These are the things that I would be thinking of. Anti–IL-17s are something that we might think about for the future. But today, what I said earlier is the approach we’re going to have to take.

Reynold Panettieri Jr, MD: Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your in-box. It comes to you wherever you’re at: on your phone, in your office, or in your home. I want to thank everyone and our sponsors for this wonderful opportunity. Have a wonderful day, and be safe. Thank you.

Transcript Edited for Clarity