Time of Day Dependent Effectiveness of Anti-IgE Therapy in Asthma: Clinical and Experimental Evidence

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.