Michael Wechsler, MD, of National Jewish Health.

Michael Wechsler, MD, MSc

"Positioning Biologics in Asthma: GINA Step 5 and Earlier Treatment" takes up where these agents sit today, and where the panel thinks they belong.

Positioning Biologics in Asthma: GINA Step 5 and Earlier Treatment

Dr. Chupp asks Dr. Hanania whether biologics remain reserved for the most severe patients or are moving earlier. Dr. Hanania starts from evidence and guidelines. The evidence sits at GINA Step 5, because that is the population enrolled in the trials he has run for years: patients with exacerbations and high biomarker profiles, studied by indication across allergic, eosinophilic, steroid-dependent, and severe asthma.

Before any biologic, he insists on documentation. Many patients are referred as severe asthma but have uncontrolled disease, or no asthma at all, sending him back to square one. Severe means high-dose ICS plus LABA plus another bronchodilator with continued symptoms, after comorbidities and triggers have been addressed. Exacerbations on top of that, or oral steroid dependence, is where biologics make a real difference. He notes four of the seven agents Dr. Wechsler described are approved for polyposis.

The agents are boxed into the 5% to 10% with severe asthma, he says, yet the concept of earlier use is very justified. Some data suggest at-risk patients with high biomarker profiles might benefit, but those studies are not published, guidelines will not embrace Step 3 or 4 use, and reimbursement follows guidelines. Clinical remission is real, reached by about 30%, but in severe patients. Whether early treatment prevents progression is unanswered.

Dr. Wechsler calls early treatment akin to preventing a fire rather than putting one out once the damage is done. His caveats are practical. Will payers fund expensive biologics earlier? Will patients accept them to prevent something that may never happen? If they would, he argues, vaccination rates would already be higher, since vaccines effectively prevent frequent exacerbations.

In "Remission in Severe Asthma: Aligning Physician Goals with Patient Goals," the panel will ask what clinicians are actually treating toward.

Videos

Evidence places biologics at GINA Step 5, and that is where reimbursement holds them. Dr. Hanania and Dr. Wechsler examine the case for moving earlier, and what it would require.

In "Seven Biologics for Severe Asthma: Targets, Timing, and Outcomes," the panel steps back for a full survey of the treatment landscape.

Biologics for Severe Asthma: Targets, Timing, and Outcomes

Dr. Chupp calls for a setup on the toolbox available, and Dr. Wechsler delivers the overview. He starts with contrast: 25 to 30 years ago the options were inhaled steroids, bronchodilators, and perhaps leukotriene modifiers. Today there are seven biologics approved for severe asthma, best understood by pathway.

Anti-IgE came first, approved in 2003, important for allergic asthma and later shown effective in urticaria and food allergy. Nothing followed until 2015, when agents targeting IL-5 arrived, then the IL-5 receptor, rolling out across 2015, 2016, and 2017 and proving very effective specifically in eosinophilic asthma. In 2025 the next generation arrived: an ultra-long-acting anti-IL-5 given just twice a year, against comparators dosed every two, four, or eight weeks, reducing exacerbations by over 50%.

Next is anti-IL-4 receptor therapy, which blocks both IL-4 and IL-13. It was approved first in atopic dermatitis in 2017, then in asthma in 2018 for severe, steroid-dependent, and type 2 phenotypes, and has since proved effective in chronic sinusitis and eosinophilic esophagitis. Two agents have crossed into eosinophilic COPD. The last class blocks TSLP. Tezepelumab has been available about five years, and works upstream, blocking downstream TH2 and ILC2 activation of IL-4, IL-5, and IL-13.

Dr. Wechsler names what the class shares. All reduce exacerbations well. All generally improve symptoms, lung function, steroid burden, and quality of life. Some patients reach remission, which he calls the next goal. Then the caveat: they are not perfect. They reduce exacerbations by 50% to 60%, leaving 40% to 50% unaddressed. They are safe, but he argues for better biomarkers, more targeted approaches, and head-to-head studies.

Our next episode, "Positioning Biologics in Asthma: GINA Step 5 and Earlier Treatment," asks Dr. Hanania where these agents belong in the treatment paradigm.

Seven approved agents across four targets, spanning two decades of approvals. Dr. Wechsler maps the class, then names the 40% of exacerbations it still does not prevent.

This episode, "Both Upper and Lower Airway Diseases," features the panel on the patients they consider their sickest.

Managing Both Upper and Lower Airway Diseases

Dr. Chupp notes patients with both upper and lower disease can be the sickest, and asks Dr. Ross how aspirin desensitization fits in the biologic era. It has changed, she says. In fellowship it was weekly, done post-surgically, and cumbersome, requiring multiple consecutive days. Biologics now reduce mediators enough that a patient with cardiac risk factors may tolerate aspirin without exacerbating. She notes a partial revival: high prostaglandin D2 patients may respond well to desensitization. Still, once patients learn the alternative is lifelong high-dose aspirin with its own risks, they choose biologics.

Dr. Wechsler frames upper airway disease as one of the comorbidities that makes asthma difficult to control. He looks for it deliberately and treats both if he can, noting some therapies favor the upper airway, some the lower, and some work in both, which makes it a real decision point.

Dr. Hanania says his group stopped aspirin desensitization entirely, because the biologic literature is now convincing. Anti-IL-5, anti-TSLP, and anti-IL-4 all work in polyposis, and polyposis itself may predict better response to anti-IL-5. He co-manages with rhinologists and allergists, images with CT sinuses, and notes most patients who have surgery continue to have polyposis.

Dr. Chupp reports the same shift at his center, with a monthly ENT conference and review of surgical pathology for eosinophil levels, which guide agent choice alongside practical differences in dosing. The biggest impact, he says, has been a drop in sinonasal surgery. Dr. Ross adds that in her area ENTs now use biologics before surgery to reduce polyp burden and improve outcomes, and observes that as a solo allergist she lacks the multispecialty access her colleagues describe.

Up next, in " Biologics for Severe Asthma: Targets, Timing, and Outcomes," Dr. Wechsler lays out the full toolbox.

Biologics have displaced a procedure that once filled the fellowship schedule. The panel weighs what replaced aspirin desensitization, and how sinus surgery rates changed with it.

"Unified Airway Disease Presentation in Clinic," takes up a question that looks different from every specialty's waiting room.

Unified Airway Disease Presentation in Clinic

Dr. Chupp asks Dr. Ross what percentage of patients presenting with nasal polyps actually have allergic sensitization, noting the field increasingly recognizes two phenotypes: the systemically allergic patient, and the patient without sensitization. Dr. Ross reaches for eosinophilic esophagitis as a parallel. She sees individuals who test positive for absolutely everything and others with identical findings who test negative to every test run. No tool yet distinguishes them. The consolation, she says, is that treatment options now exist for either end result. She estimates about 75% of her patients have some allergy driving their phenotype, while conceding her office is skewed; her non-allergic patients likely land in the ENT office instead.

Dr. Wechsler says the distinction is genuinely hard, and clinicians often treat for one, then the other. Patients referred to him with asthma and sinus disease frequently arrive after a course of antibiotics that may not have helped what is actually a type 2 inflammatory problem. Around 30% to 40% of his asthma patients have concomitant upper airway disease, and treating it aggressively pays off in both directions.

Dr. Ross argues specialists must go beyond the presenting complaint, because a good history teases out polyps, sinus issues, repeat surgeries, and antibiotics. Dr. Wechsler adds that it is not difficult: ask about sense of smell, the best single indicator of upper airway disease.

Dr. Hanania reports his CRS and polyp patients skew non-allergic with late-onset asthma and significant polyposis, and roughly 15% have aspirin or NSAID-exacerbated disease. He describes starting multidisciplinary discussions with rhinology and allergy, calling cross-specialty communication an area still raw in practice.

In "Managing Both Upper and Lower Airway Diseases," the panel will ask what happens to aspirin desensitization once biologics arrive.

Not every patient with nasal polyps is allergic, and no test reliably separates those who are. The panel discusses how referral patterns skew what each specialist believes.

Michael Wechsler, MD, MSc

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