Monday afternoon’s session, Biologics in Asthma, drew a big crowd. With several approved biologics for the treatment of asthma (primarily T2 asthma)—and others in the pipeline—the topic is hot. This session discussed how biologics work in the body, how to assess patient response, and ways in which clinicians should reframe the concept of remission.

Diego J Maselli Caceres, MD, FCCP opened the session by saying biologics have drawn “increased interest—and some controversy.” There are currently six approved biologics for asthma: Omalizumab, Mepolizumab, Reslizumab, Benralizumab, Dupilumab, and Tezepelumab. Biologics are generally considered safe—and they can be effective in improving rates of exacerbation, lung function, OCS dependency, and symptoms, he explains.

 

Choosing & switching biologics

 

“The million dollar question is how do we choose amongst these fantastic medications?” he asked. “It’s not a simple question.”

 

He then offered up a “patient” to the room: A 36-year-old female with severe asthma, allergic rhinitis, and frequent exacerbations. She has a good response to prednisone, she’s compliant with ICS/LABA/LAMA, PFTs show a ++ BDR, FEV1 60%, ACT 14 and AIRQ 8. She’s got 310 cells/microfilter, 30 PPB FeNO, she’s allergic to trees, grass, and cats, and her IE is 240 IU/ml.

“It is difficult, but this is a patient you will encounter in your practice frequently,” Dr. Maselli continued. “How do we choose [a biologic] when there aren’t any head-to-head trials?” He says the most important things to consider when selecting a biological are:

• Patient biomarkers 

• Comorbidities 

• Corticosteroids dependency

• Safety and Pregnancy

The biologics on the market have differing targets and treatable traits. Each biologic is also approved in other disease states, so you’ll want to be sure to know how each differs.

• Omalizumab (targets IgE, IgE level (30-70 IU ml) + perennial allergies

• Mepolizumab (targets IL-5, eosinophils >150 cells /mL)

• Reslizumab (targets IL-5, eosinophils >400 cells /mL)

• Benralizumab (targets IL-5R, eosinophils >150 cells /mL)

• Dupilumab (targets IL-4R, eosinophils >150 cells /mL of FeNO >25 ppb)

• Tezepelumab: Targets thymic stromal lymphopoietin, or TSLP—no biomarker needed. 

Certain biologics will lead to different results. For example, Dupilumab and Tezepelumab result in lower FeNO, so a patient with high FeNO may be better suited to those.

Switching biologics is safe as well, Dr. Maselli said. But it's a matter of knowing when. You’ll want to assess symptoms and biomarkers. Muhammad Adrish MBA, MD, FCCP referred back to the original patient, who is on Mepolizumab but isn’t exactly where her MD wants her to be. Would the room switch her biologic? The crowd seemed unsure.

 

According to the Global Initiative for Asthma (GINA), if it’s unclear whether a patient is responding, extend the trial for 6-12 months, then choose another biologic and assess for the four months. If not, stop the biologic use and consider switching to a different T2-targeted therapy. Dr. Adrish says you can switch a patient out fairly quickly, as there’s a half-life ranging from 15-30 days for most of the current biologics. 

Biologics fail for a bunch of reasons, too, including improper phenotyping, multiple inflammatory pathways, inadequate dosing, nonadherence to baseline controller or biologic therapy, and the presence of circulating antibodies to the biologic. 

There are racial differences, too. Dr. Adrish says. “It’s worth noting that non-Hispanic Blacks have a high incidence of asthma exacerbation. This is something to keep in mind when starting or switching biologics,” he says. When the biologics do seem to be working well, he suggests tapering controller therapy and continuing the biologic for 12 months before reassessing.  

In summary, he encourages timely identification of non-responders to minimize uncontrolled asthma and a personalized approach to switching biologics while considering the patient. “Let’s find out what the best biologic is for the patient, but also what are the barriers these patients are facing to get biologics,” he says. 

 

Exploring remission: a paradigm shift is necessary

 

Lastly, Njira Lucia Lugogo, MD, discussed the concept of remission in asthma, and how it relates to biologics. “Assessing response is multifaceted..and that’s exactly what remission is,” she says. She refers to concepts of remission in diseases like cancer, diabetes, or rheumatoid arthritis—but in asthma, it’s a little different. 

She said that MDs need to get ahead of this cycle. “The treatment is predicated on the patient complaining. If they don’t complain or if the patient isn’t on high-intensity therapy…that patient may be horribly undertreated,” she said. 

Breaking this cycle and avoiding organ damage and extrapulmonary damage from corticosteroid exposure is the goal. 

“We have to make a diagnosis, assess risk, mitigate risk by treating asymptomatic inflammation, preserve lung function and reduce airway remodeling…and reduce corticosteroid use,” she says. 

In short, “We have to predict and prevent to achieve remission. We need to embrace a new paradigm where we want every patient to have the best possible outcome,” Dr. Lugogo adds. She notes that spontaneous remission is not a frequent finding.

She wants clinicians to know that it’s not enough to ask how a patient is doing and then move on, and that assuming a lack of symptoms means no disease activity is also unhelpful. 

She reminds the room that asthma therapy has seen a lot of change over the decades, from the beta-agonists of the 1960s to the biologics today. There is a lot of hope and potential. With biologic therapy, a real-study showed that after 12 months, “79% of patients had clinical response, and 24% of those patients achieved clinical remission,” according to NEJM Journal Watch. 

Dr. Lugogo also made the case for trusting patients on how they perceive their disease. “Our assumption is that our patients don’t get it, or it’s too complicated. I think patients are actually ahead of us. They believe in remission. And if they give us a goal of remission they’ll hold us accountable for helping them.”