Does One Mab Come Out on Top for Boosting Lung Function in Asthma?

PHOENIX — In some patients with eosinophilic asthma, dupilumab (Dupixent) offered the highest chance of better lung function, although the agent also carried the highest odds of serious adverse events (AEs), a researcher reported.

In an indirect treatment comparison of dupilumab, mepolizumab (Nucala), and benralizumab (Fasenra), patients with eosinophil counts ≥300 cells/μL treated with dupilumab had the highest probability of decreased exacerbations and improved pre-bronchodilator lung functioning, according to Ayobami Akenroye, MBChB, MPH, of Brigham & Women’s Hospital in Boston, but the agent also came with serious AEs as outlined in previous research.

However, in patients with eosinophil counts 150 to <300 cells/μL, benralizumab had the highest overall probability of improving lung function and exacerbation rates, followed by dupilumab for preventing exacerbations, and mepolizumab for improving lung function, she said in a presentation at the American Academy of Allergy, Asthma & Immunology annual meeting.

Ultimately, “the difference between [the three agents] was small. There was no overall clear favorite,” Akenroye noted.

Akenroye estimated that 2.8% of asthma patients in the U.S. and more than 80% of those with severe asthma may be eligible for one of the six currently approved biologics.

But “evidence on comparative efficacy or effectiveness is sparse and inconclusive,” she said.

For the indirect treatment comparison, Akenroye and colleagues used a Bayesian framework and pulled relative effect estimates (treatment vs placebo) from eight randomized trials of the three agents, which included a total of 6,461 patients.

Study limitations included the possibility of ecological fallacy as there were no individual-level data. Also, there was no direct evidence so the authors were not able to evaluate consistency. And there was different distribution of effect modifiers, along with the potential for different placebo effects.

William Anderson, MD, of Children’s Hospital Colorado/University of Colorado in Aurora, told MedPage Today that cross-study comparisons like this need to be taken with caution.

“We as physicians try to use whatever evidence base is available that can help us make these decisions about what drug is best for our patients,” he said. “I think Dr. Akenroye did a great job in explaining the limitations with her analysis, and the limitations of these indirect comparisons, but that is opening the doorway to these comparison studies. I hope more research is done in the field like this so we can find the best tailored medication for our patients.”

As for the risk-benefit trade-off with dupilumab, “I think you have to have this conversation with the patient about the risk-benefit ratio and what are those [AEs],” stressed Anderson, who was not involved in the study. “I think as a clinician, you have to be diligent in watching for the [AE] symptoms that have been described with these biologics, and to let the patients know in advance about what to expect in terms of side effects. No medicine comes without that risk-benefit balance.”

Anderson also wondered how tezepelumab (Tezspire), which was not included in the analysis, would fit into the equation. The agent received FDA approval late last year for use as add-on maintenance therapy for patients ages 12 and older with severe asthma.