Tezepelumab reduces mucus plugs, improves lung function in adults with asthma
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Key takeaways:
- Reductions in mucus plug scores correlated with reductions in fractional exhaled nitric oxide levels.
- These reductions also were associated with increased prebronchodilator FEV1.
Adults with moderate to severe uncontrolled asthma experienced reductions in mucus plug scores with tezepelumab, according to a study published in NEJM Evidence.
These reductions also correlated with improvements in lung function, Lars H. Nordenmark, PhD, senior clinical scientist, late-stage development, respiratory and immunology, biopharmaceuticals R&D, AstraZeneca, and colleagues wrote.
The cohort comprised 82 patients from the CASCADE study who had multidetector CT imaging at baseline and after receiving 210 mg of subcutaneous tezepelumab (Tezspire, Amgen/AstraZeneca; n = 37) or placebo (n = 45) every 4 weeks for at least 28 weeks.
At baseline, 21 (56.8%) of the treatment group and 14 (31.1%) of the placebo group had mucus plugs. At the end of treatment, 37.8% of the treatment group and 13.3% of the placebo group had transitioned from at least one mucus plug to no mucus plugs.
Additionally, mean absolute changes in mucus plug scores included –1.7 ± 2.6 in the treatment group and 0.0 ± 1.4 in the placebo group.
These reductions in mucus plug scores correlated with reductions in blood eosinophil counts for the treatment group (Spearman’s rank correlation coefficient [r] = 0.28) but not for the placebo group (r = 0.09).
Similarly, these reductions correlated with reductions in fractional exhaled nitric oxide levels for the treatment group (r = 0.27) but not for the placebo group (r = –0.11).
Reductions further correlated with increases in prebronchodilator FEV1 for the treatment group (r = –0.51) but not for the placebo group (r = 0.02).
These correlations persisted with increases in forced expiratory flow rate between 25% and 75% or FEF25-75% in the treatment group (r = –0.54) but not in the placebo group (r = 0.04) as well.
The treatment group also saw correlations between reductions in mucus plug scores and reductions in plasma (r = 0.51) and in and bronchoalveolar lavage (BAL) eosinophil-derived neurotoxin (EDN; r = 0.47), but the placebo group did not (r for plasma = –0.05; r for BAL EDN = –0.3).
Finally, these reductions correlated with greater lumen area for airway generations 4 (r = –0.41) and 5 (r = –0.44) in the treatment group but not in the placebo group (r for generation 4 = –0.21; r for generation 5 = –0.05).
Based on these findings, the researchers concluded that these reductions in mucus plugs are part of the salutary therapeutic effect that tezepelumab has on patients with uncontrolled mild to moderate asthma.
Perspective
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The findings are not necessarily surprising because we know that tezepelumab is effective in treating severe asthma, but they are significant because they confirm that the medication is improving plugs of mucus in the airways. These mucus plugs are one of the ways that asthma can cause problems with breathing. The study also confirms that close examination of CT scan is one key way to study the impact of biologic medications for asthma, at least in the research setting.
Also, these findings confirm my experience that tezepelumab works well for many patients. I would expect similar findings with some of the other biologic treatments for asthma. Doctors can use these findings to call attention to the fact that small mucus plugs are an underappreciated feature of more severe asthma.
I would be interested in seeing if CT scans could be even more incorporated into clinical care of asthma with careful scoring of mucus plugs, which may prove helpful with decision-making in starting biologic therapy.
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