Response to biologics may vary for patients with asthma, obesity
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Key takeaways:
- Exacerbations fell with omalizumab and mepolizumab for patients with asthma and obesity.
- Obesity did not decrease dupilumab’s rate of response in treating asthma.
- Tezepelumab may address type 2 low asthma.
BOSTON — Patients with obesity and asthma may see reductions in exacerbations with biologic treatment, according to a presentation at the CHEST Annual Meeting.
“Obesity and asthma have multiple kinds of interactions,” S. Shahzad Mustafa, MD, chief of allergy, immunology and rheumatology at Rochester Regional Health, said during his presentation.
Mechanical forces, poor diet, oxidative stress, immune dysfunction and impaired metabolism all have an impact on interactions between obesity and asthma, he said, adding that steroid responsiveness, resistance and clearance also influence these interactions.
“We’ve been taught that adipose tissue is steroid-resistant. No so much so,” Mustafa said. “Adipose tissue actually increases steroid clearance. So, in a way, that’s steroid resistant.”
Mustafa advised physicians that they will not get as much “bang for your buck” with systemic steroids with patients with asthma and increasing BMI as a result.
Omalizumab (Xolair; Genentech, Novartis), dupilumab (Dupixent; Regeneron, Sanofi) and mepolizumab (Nucala, GSK) have varying effectiveness among patients with asthma and obesity, Mustafa said.
Compared with placebo in one retrospective analysis, adjusted exacerbation rates with omalizumab decreased by 37% for patients with BMI less than 25 kg/m2, by 53% for patients with BMI between 25 kg/m2 and less than 30 kg/m2, and by 72% for patients with BMI of 30 kg/m2 and above.
“We see a lot of people well over 30 kg/m2,” he said.
But in a prospective study of patients with chronic spontaneous urticaria, those with higher BMI were more likely to see treatment with omalizumab fail to decrease their exacerbation rates. Another post-hoc analysis found that comorbidities such as nasal polyposis and obesity decreased likelihood of response to omalizumab as well.
However, Mustafa noted that the conclusions related to omalizumab were based on “really suboptimal data.”
In another post-hoc analysis, obesity as an independent risk factor did not decrease dupilumab’s rate of response. Instead, Mustafa said, high eosinophil counts and fractional exhaled nitric oxide indicated better response to treatment.
“Sometimes people hesitate on starting dupilumab in individuals with higher eosinophil counts, but it’s actually the only biologic that doesn’t deplete eosinophils,” Mustafa said.
Patients with asthma and BMIs of 25 kg/m2 or less, 25 kg/m2 to 30 kg/m2, 30 kg/m2 to 36 kg/m2, and 36 kg/m2 and higher all saw reductions in annual rates of clinically significant exacerbations with mepolizumab as well in another post-hoc study.
“The general takeaway is these biologics probably do maintain efficacy in individuals with higher BMI,” Mustafa said.
But he cautioned that discussions about which biologic to use for patients with asthma and obesity will be nuanced. He also suggested that artificial intelligence may be useful in helping physicians and patients choose which biologic to use.
Mustafa added that he would be remiss to leave tezepelumab (Tezspire; Amgen, AstraZeneca) out of the conversation about asthma with a type 2 low phenotype, even though there were very few data pertaining to its use in relation to obesity and asthma.
“But if you think about tezepelumab in a T2 low phenotype in individuals with low IgE and low eosinophils, that may make sense in this space,” he said.
References:
- Albers FC, et al. Respir Res. 2019;doi:10.1186/s12931-019-1134-7.
- Busse WW, et al. Eur Respir J. 2021;doi:10.1183/13993003.04605-2020.
- Geng B, et al. Ann Allergy Asthma Immunol. 2022;doi:10.1016/j.anai.2022.01.025.
- Ghazanfar MN, et al. Clin Exp Allergy. 2022;doi:10.1111/cea.14121.
- Sposato B, et al. Eur J Intern Med. 2018;doi:10.1016/j.ejim.2018.01.026.