Time-of-Day–Dependent Effectiveness of Anti-IgE Therapy in Asthma: Clinical and Experimental Evidence
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Background
Asthma is a time-sensitive inflammatory disease whose activity exhibits daily (circadian) rhythms. An outstanding question is whether such temporal variations extend to advanced asthma treatments like biologics that are used for moderate-to-severe disease.
Objective
To examine how time-of-administration relates to the effectiveness of the anti-IgE biologic, omalizumab.
Methods
We performed a retrospective cohort study of omalizumab effectiveness in 153 patients with asthma with timestamped administration records. Time of day was modeled as a continuous variable and dichotomized into morning (8:00-11:59, n=74) versus afternoon (12:00-17:00, n=79) administration. Multivariable logistic regression and Cox time-to-event analyses were used to adjust for key covariates. For biological validation, we treated ovalbumin (OVA)-sensitized mice with anti-IgE antibody at various times of day and measured its impact on inflammatory lung pathology.
Results
Receiving the initial dose of omalizumab in the afternoon was associated with better response, defined as a 50% or more reduction in asthma exacerbations in the year after initiation (Odds ratio, OR: 5.20; 95% CI, 1.94−13.96). For each hour later in the day the initial dose of omalizumab was given, the odds of a response increased by 34% (adjusted OR, 1.34; 1.02–1.77). In OVA-sensitized mice, anti-IgE treatment attenuated inflammatory lung pathology, including OVA-induced airway hyperresponsiveness and type-2 inflammation-related gene expression, in a time-of-day-sensitive manner, with maximum effectiveness when dosed in the latter part of the dark phase, functionally analogous to the afternoon in humans.
Conclusion
The timing of anti-IgE treatment for asthma may influence therapeutic success. These findings have implications for optimizing the effectiveness of respiratory biologics.
Take-home messages
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IgE-targeted therapy in patients with asthma and in murine experimental asthma varied in effectiveness based on administration time.
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In patients, receiving the first omalizumab dose in the PM (vs. AM) was associated with better treatment response.
