Experts debate the role of biologics in asthma treatment
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NASHVILLE, Tenn. — Experts found both consensus and contention during a roundtable discussion of the use of biologics to treat severe asthma, modelled on the ESPN program “Pardon the Interruption,” during the CHEST Annual Meeting.
David Schulman, MD, MPH, professor in the division of pulmonary, allergy, critical care and sleep medicine at the Emory School of Medicine and president of the American College of Chest Physicians, moderated the panel and kicked off the debate by asking which biologic is the best choice for patients with severe asthma, allergy and elevated eosinophils.
“It depends on really not just their phenotype, but also what their clinical history is,” Sumita Khatri, MD, director of the Asthma Center at the Cleveland Clinic, said to open the discussion, emphasizing the need to listen to the patient. “Don’t just go with the one that the last drug rep has come in to peddle to you.”
When Khatri suggested that omalizumab (Xolair, Genentech/Novartis) could be used for patients dealing with seasonal or perennial allergies, Frances Eun-Hyung Lee, MD, associate professor of medicine at the Emory School of Medicine, asked about using dupilumab (Dupixent, Sanofi Genzyme/Regeneron) as an alternative.
“Do you think there is any benefit in those patients who have allergy and eosinophils to go with dupilumab because of the fact that it inhibits IgE formation as well as all of these other effects in terms of the IL-13 pathways?” Lee asked.
Monica Kraft, MD, Murray M. Rosenberg Professor of Medicine and system chair of the department of medicine at the Icahn School of Medicine at Mount Sinai, said she liked that idea but would really need more information.
“The phenotype would help to figure that out,” Kraft said. “Do you think allergy is the driver?”
“I think they’re all wrong,” Mario Castro, MD, MPH, L.E. Phillips and Lenora Carr Phillips Professor at the University of Kansas Medical Center and adjunct research professor at the University of Missouri-Kansas City School of Medicine, said, tongue in cheek, about his colleagues. “It’s whatever the payers are going to let us prescribe. That is the answer.”
“The ‘doc in the box’ — you have to convince them that your patient needs this particular biologic,” Kraft responded. “That’s a problem.”
Determining effectiveness
Next, Schulman asked the panel what objective data they use to determine whether a biologic has been effective. Lee noted that while studies examine endpoints such as FEV1 and exacerbation rates, communication matters too.
“It’s also important to ask the patient, ‘How do you feel? Do you have increased exercise tolerance? Do you feel better? Are your symptoms better? Do you have less sputum production?’ Those things are really important,” she said. “It’s not one single factor.”
Kraft agreed, adding that physicians need to decide if exacerbations or other factors are causing the patient’s symptoms. Physicians also need to wait before they decide if the biologic has been effective, she said.
“You have to figure out what are the major drivers of that patient’s asthma and then be able to assess over a period of time of 4 to 6 months,” she said.
Khatri brought up the importance of shared decision-making in discussing these issues with patients.
“What really matters to them?” she asked. “Do they want to be active? Do they mind a little bit of steroids, or do they want to be off steroids altogether? Also, how often do they want to give themselves shots? That often has to go into the mix as well.”
Castro commented on steroid use as well.
“Patients hate steroids, right? And we don’t like giving them, but exacerbations are driving our steroid use,” Castro said. “This is the most important thing for a lot of my patients. Can I get them off steroids? Can I avoid steroids for an exacerbation?”
When Schulman then asked the panel if they would continue treatment when patients say they feel better but the objective data says otherwise, Lee and Khatri said they would continue treatment, whereas Castro and Kraft said they would switch.
This split response prompted Schulman to ask the panel how long they would continue treatment with a biologic before considering a change in management.
“You don’t want to continue an expensive med longer than you need to,” Kraft said. “It depends on what you’re looking at. If you’re looking at exacerbations, if they’ve had a couple a year, you might need at least 6 months [or longer] to really assess a change.”
Khatri agreed that it depends on the patient, describing an example of a patient who may be on steroids for a long time and new to biologics but hesitant that they might not get better.
“I’ll actually talk to them ahead of time and say that normally I do wait 6 months or a little bit longer because success breeds success. But in your case, yours is so severe that I would switch at 3 months if this is not actually working for you,” Khatri said. “Having these conversations at the get-go is very important.”
Castro thought that 3 months was a quick timeframe.
“I went through all that paperwork to get it authorized,” he said, again tongue in cheek. “Do you think I’m going to change at 3 months?”
Lee pointed out that benralizumab (Fasenra, AstraZeneca) has a very early effect due to a loss of terminal cells in the blood and airways, whereas dupilumab and other biologics could take 3 to 6 months.
“With dupilumab, what I find typically is that IgE levels don’t fall in those patients until later. I know that wasn’t their endpoint. It may take a little while for those upstream mediators to actually have an effect, immunologically, in those patients,” Lee said.
Still, Lee continued, some patients may need even longer.
“In terms of two exacerbations a year, is 6 months long enough?” Lee asked.
The role of controller medications
Considering this consensus, Shulman asked if physicians should taper other controller medications when patients do well on biologics for asthma.
“Definitely,” Castro said. “I tell patients, ‘Let’s get rid of the steroids first.’ And once we’re able to get rid of the steroids, or get them to a low-dose inhaled corticosteroid, ultimately, I switch them to smart therapy and try to minimize their steroid exposure.”
Castro clarified that he does not tell his patients to stop steroids altogether, because the insurance company may then stop paying for the biologic, even though it has worked well, but minimizing their use is still the ultimate goal.
But Kraft asked what doctors should do when it is time to renew these prescriptions.
“My patients sometimes will stop their controllers, whether we talk about it or not. Then it comes time to renew, and the carriers have figured out that they’re not renewing their inhaled corticosteroids. So then, what do you do?” she asked.
The biologic then becomes a very expensive controller medication, Khatri said, adding that physicians have to be responsible for these decisions.
“Hopefully, one day we’ll find that biologic that’s disease-modifying and you can get a shot and keep going. But this is like the price of a car, a really nice car, per year. We need to think about the cost,” Khatri said.
Khatri brought up issues specific to postmenopausal women with asthma who may be obese as well.
“They come in and nobody believes they have asthma. Nobody believes that until you do a methacholine challenge,” she said. “Then you give them azithromycin or anti-leukotriene, and they feel better. And you know what? I am so done with women being ignored after menopause.”
Kraft added that she would like to see data on tapering controllers during treatment with biologics to evaluate what could be done safely.
“We can go to carriers and say, ‘Hey, we’ve got something that works. It’s safe, and it’s a lot better than steroids,’” she said. “So, let’s get some data.”
“The question is if you have two drugs that act on the same target, and inhaled corticosteroids are affecting some of the T2 cells as well as the biologics, should you be using both of those medications?” Lee said.
Castro then described how some patients have used montelukast (Singulair, Merck) for aspirin-exacerbated respiratory disease for years without effect, whereas others have used high-dose aspirin therapy even though they hate it.
“Now we have biologics that are very effective for upper airway disease,” Castro said. “I think that the patients tell us what’s working and, ultimately, that’s a good thing.”
Reference:
- ACCP Chest. Pardon the interruption 2022: Controversies in asthma. https://www.youtube.com/watch?v=CRbYX-K1m2Y. Published Oct. 17, 2022. Accessed Oct. 19, 2022.