No Evidence to Guide Selection of Biologic for Severe Asthma

Ingrid Hein

October 30, 2020

Although "biologics have been really revolutionary for the treatment of severe uncontrolled asthma, we still don't have evidence to know the right drug for the right patient," said Wendy Moore, MD, from the Wake Forest School of Medicine in Winston-Salem, North Carolina.

Wendy Moore

"You start with your best guess and then switch," she told Medscape Medical News.

There are no real-world contemporary measurements of biologic therapy in the United States at this time, Moore explained during her presentation of findings from the CHRONICLE trial at CHEST 2020.

The agents have different targets: omalizumab targets immunoglobulin E, mepolizumab and reslizumab target interleukin (IL)-5, benralizumab targets the IL-5 receptor, and dupilumab targets the common receptor IL-4 receptor A for IL-4 and IL-13.

When the starting biologic doesn't get the desired results, there is no evidence to show whether another will work better. What we say is, "this one is not working as well as I'd like, let's try something new?" said Moore.

However, when looking at data on patients with severe asthma who change from one biologic to another, "I was actually pleased to see that only 10% are switching," she told Medscape Medical News.

But, she added, "if you add that up with the 8% who are stopping, that means that almost 20% don't get the clinical response they want."

CHRONICLE Trial

In the ongoing observational CHRONICLE trial, Moore and her colleagues assessed biologic initiations, discontinuations, and switches to a different agent.

All 1884 study participants had a diagnosis of severe asthma and were being treated by an allergist/immunologist or a pulmonologist. All were taking high-dose inhaled corticosteroids and additional controllers, or had received an FDA-approved monoclonal antibody, systemic corticosteroid, or another systemic immunosuppressant for at least half of the previous 12 months.

In the study cohort, 1219 participants were receiving one biologic and 27 were receiving two.

Before November 2015, "it was almost universally all benralizumab being prescribed." Omalizumab was prescribed to 99% of patients before November 2015 and to 45% from November 2017 to November 2018.

"As new drugs were introduced, patients were switched if the desired outcome was not achieved," Moore explained.

Over the 2-year period from February 2018 to February 2020, 134 patients — about 10% of all participants taking a biologic — made 148 switches to another biologic.

"The most common reasons reported for switching were lack of efficacy, worsening of asthma control, or waning efficacy," Moore reported.

Of the 101 patients (8%) who discontinued 106 biologics, reasons cited were a worsening of asthma symptoms, a desire to change to a cheaper medication, and a waning of effectiveness.

I don't think we totally understand the perfect patient for any one of these drugs.

"It seems that the biologic used depended on when you started and whether you were prescribed by an immunologist or pulmonologist," said Moore. "I don't think we totally understand the perfect patient for any one of these drugs."

Large-population studies need to be done on each of the drugs. "You have to look at who's the super responder, the partial responder, compared with the nonresponders, for each medication, and those comparative studies are unlikely to happen," she said.

In her own practice, her 175 patients are "pretty evenly split between dupilumab, benralizumab, and mepolizumab."

I have opinions on what works, said Moore, but none of it is evidence-based. "Those with upper airway involvement with chronic sinusitis tend to do better with mepolizumab than benralizumab. My opinion," she emphasized.

"People with nasal polyps may do better with dupilumab and mepolizumab," she added. "Also in my opinion.

"But more likely, the issue is you have a partial responder who's on a T2 high drug but has a T2 low problem too."

PATHWAY Study

Findings from the phase 2B PATHWAY study showed that tezepelumab reduced exacerbations in patients with uncontrolled asthma better than inhaled corticosteroids, and improved forced expiratory volume in 1 second (FEV₁).

"Adherence was monitored very carefully," said investigator Jonathan Corren, MD, from the University of California, Los Angeles, who presented the PATHWAY data. This could explain, in part, why some patients in the control group "showed improvement from baseline."

Before switching to a biologic, "we should always consider some of these issues that might contribute to better asthma control, like patient adherence or the inability to use an inhaler properly," Corren said.

Some people have never been "shown how to use their inhalers properly," said Moore. "Some of them come back fine when we show them."

Moore has been on the advisory board for AstraZeneca, Genentech, GlaxoSmithKline (GSK), Regeneron, and Sanofi. Corren reports receiving honoraria from AstraZeneca.

CHEST 2020: American College of Chest Physicians Annual Meeting. Presented October 20, 2020.

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