Clinicians are often faced with a clinical conundrum: Which biologic for which severe asthma patient? This issue came up a lot at the CHEST conference this year. CHEST Journal even published a “How I Do It” about this very issue, in which clinicians explore why they choose one over the other when no head-to-head trials exist. After all, there are six biologics on the market

• 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. 

To begin answering the question of “which biologic?” a Tuesday afternoon session offered up the “first guideline regarding the choice of biologics in severe asthma published,” drawn up by CHEST cochairs, panelists, methodologists, and guideline development experts. Their goal was to offer evidence-based recommendations and expert panel consensus. 

As the session began, the session hosts first polled the room on a series of biologics-related questions. The overwhelming responses were—to paraphrase—that almost everyone wanted guidance on all aspects of biologics, that most clinicians chose Dupilumab, followed by Mepolizumab, that most clinicians chose Dupilumab for patients with steroid-dependent asthma, and that most clinicians waited 5-6 months before determining a patient has an inadequate response to their biologic. Basically, the room was hungry for guidance. 

In developing the CHEST guidelines, Dr. Oberle said the goal was simple: 

“Take a complex topic and distill it down to a digestible topic.” To achieve that purpose, they eliminated the age factor for the session’s discussion. 

Manoj Mammen, MD, discussed a bit about the guideline methodology, saying they started with a PICO question and built their panel from people with diverse sets of interests and no conflict of interests. He also went over some of the language they used around their recommendations. 

For example, the word “suggests,” means a low certainty of evidence to back-up their recommendation. They also used the “conditional recommendation” in their guidelines frequently due to a lack of evidence and lack of head-to-head data on the biologics. He even displayed a Pirates of the Caribbean graphic on the screen, saying “It’s more of a guideline than a rule.” 

They then shared their recommendations to a set of PICO questions (the guidelines are currently being peer-reviewed and will be available in the future). However, a selection of their new recommendations are below: 

• Allergic asthma: In patients >18 with moderate to severe allergic asthma and history of >1 exacerbation requiring oral corticosteroids, the panel suggests using either Omalizumab or Dupilumab. This is a conditional recommendation due to a very low certainty of evidence. 

• Allergic asthma with frequent exacerbations: For patients with frequent exacerbations (greater than or equal to 2) or any severe exacerbation requiring hospitalization, the panel suggests Dupilumab over Omalizumab. This is a conditional recommendation due to a very low certainty of evidence. 

• Allergic asthma with low lung function:  For patients with a greater impairment in lung function (fev1 <70% predicted), the panel suggests Dupilumab over Omalizumab. This is a conditional recommendation due to a very low certainty of evidence. 

• Steroid-dependent asthma: In patients >18 with severe asthma who are steroid dependent, the panel suggests either anti-IL5/Ra therapy or Dupilumab, and over Tezepelumab. This is a conditional recommendation due to a very low certainty of evidence. 

• Second line choices: In patients >18 with severe asthma who have not demonstrated a clinical response to Dupilumab, the panel suggests anti-IL5/Ra or Tezepelumab. In steroid-dependent patients, the panel suggests -IL5/Ra therapy over Tezepelumab. This is a conditional recommendation due to a very low certainty of evidence. 

Dr. Oberle also reminded the room to think about why patients are failing their biologics. “Are our patients adhering to therapy? What about modifiable comorbidities? And, are we sure we are even treating asthma?” she asked the room. 

To help determine biologic choice or switch, Frederic Little, MD also stressed the importance of going back to the drawing board and examining the patient’s pre-treatment biomarker data.   

The panelists said that sometimes it can be tempting to skip over low-certainty guidelines or evidence and get to the good stuff, but Dr. Little responded to that saying, it’s still helpful. “These guidelines help us go down that next step and push us to use agents we aren’t familiar with. We can advocate for our patient to get that home run.” 

He notes that clinicians have to pick the best biologic first, because weeks and months of approval barriers are a challenging reality for patients.