Omalizumab is ineffective in regulating proasthmatic serum cytokine and chemokine levels in nonresponders with high BMI

Abstract

Background: Omalizumab provides clinical benefits to a fraction of patients with asthma. It remains unclear why some patients do not respond to omalizumab therapy.

Objective: We sought to investigate whether omalizumab could alter serum cytokine and chemokine levels that could be associated with asthma pathogenesis. We also investigated why omalizumab is ineffective in controlling proasthmatic serum cytokine and chemokine levels in nonresponders.

Methods: Serum cytokine and chemokine levels in patients with moderate to severe asthma (N = 45; 34 responders and 11 nonresponders) were assessed before and after 26 weeks of omalizumab therapy. Correlations between cytokine and chemokine levels and asthma symptoms as well as characteristics of responders and nonresponders were assessed. Nonasthmatic subjects (N = 22) served as controls for patients with asthma (N = 45).

Results: Omalizumab was more effective in patients with increased serum eotaxin-1 and IL-13 levels than in others at baseline. Omalizumab decreased eotaxin-1 and IL-13, along with levels of most of the cytokines and chemokines tested, including IL-7, CCL17, and CXCL10, in responders, except for CCL5 and CCL22, which can contribute to neutrophilic and type 2 airway inflammation, respectively. In contrast, omalizumab did not decrease such serum cytokine and chemokine levels in nonresponders. Of interest, serum CCL17, CCL22, CXCL10, and IL-7 levels in nonresponders were associated with their body mass index, which could explain why omalizumab was unable to reduce their concentrations in nonresponders.

Conclusions: Omalizumab can regulate most cytokine and chemokine levels in responders. However, in nonresponders, it is unable to modulate specific proasthmatic cytokines and chemokines due to their association with individual body mass index, which is not influenced by omalizumab.

Keywords: Asthma; IgE; anti-IgE; body mass index; chemokine; cytokine; omalizumab; serum.

Fig 1

Serum levels of CCL17 (A) and CXCL10 (B) at baseline as well as CCL22 (C) and IL-7 (D) at week 26 correlate with the BMI of nonresponders (N = 11), but not responders (N = 34). Simple linear regression test was used to determine significance.

Fig 2

Serum IL-7 level (A) at week 26 inversely correlates with ACT scores of nonresponders (N = 11), but not responders (N = 34). Correlations between ACT scores and serum CCL17 (B), CCL22 (C), and CXCL10 (D) levels at week 26 are also presented. Simple linear regression test was used to determine significance.