Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma

Abstract

Rationale: Allergic inflammation has been linked to increased susceptibility to viral illnesses, but it is unclear whether this association is causal.

Objectives: To test whether omalizumab treatment to reduce IgE would shorten the frequency and duration of rhinovirus (RV) illnesses in children with allergic asthma.

Methods: In the PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study, we examined children with allergic asthma (aged 6-17 yr; n = 478) from low-income census tracts in eight U.S. cities, and we analyzed virology for the groups randomized to treatment with guidelines-based asthma care (n = 89) or add-on omalizumab (n = 259). Weekly nasal mucus samples were analyzed for RVs, and respiratory symptoms and asthma exacerbations were recorded over a 90-day period during the fall seasons of 2012 or 2013. Adjusted illness rates (illnesses per sample) by treatment arm were calculated using Poisson regression.

Measurements and main results: RVs were detected in 97 (57%) of 171 exacerbation samples and 2,150 (36%) of 5,959 nonexacerbation samples (OR, 2.32; P < 0.001). Exacerbations were significantly associated with detection of rhinovirus C (OR, 2.85; P < 0.001) and rhinovirus A (OR, 2.92; P < 0.001), as well as, to a lesser extent, rhinovirus B (OR, 1.98; P = 0.019). Omalizumab decreased the duration of RV infection (11.2 d vs. 12.4 d; P = 0.03) and reduced peak RV shedding by 0.4 log units (95% confidence interval, -0.77 to -0.02; P = 0.04). Finally, omalizumab decreased the frequency of RV illnesses (risk ratio, 0.64; 95% confidence interval, 0.49-0.84).

Conclusions: In children with allergic asthma, treatment with omalizumab decreased the duration of RV infections, viral shedding, and the risk of RV illnesses. These findings provide direct evidence that blocking IgE decreases susceptibility to RV infections and illness. Clinical trial registered with www.clinicaltrials.gov (NCT01430403).

Keywords: IgE; asthma; omalizumab; rhinovirus.

Figure 1.

The PROSE (Preventative Omalizumab or Step-up Therapy for Severe Fall Exacerbations) study nasal samples Consolidated Standards of Reporting Trials diagram for the intention-to-treat population (n = 348).

Figure 2.

Comparison of rhinovirus (RV) detection in exacerbation versus nonexacerbation samples. The graphs depict (A) the prevalence of RV detection in exacerbation versus nonexacerbation samples and (B) the odds ratio (OR) (95% confidence interval [CI]) between exacerbation samples with RV detection versus no RV detected.

Figure 3.

Omalizumab effects on viral detection. Bars represent omalizumab versus placebo effects on (A) rhinovirus (RV) prevalence (odds ratio and 95% confidence interval) and (B) peak viral shedding (log₁₀ difference and 95% confidence interval). The counts represent the number of participants with at least one virus sample detected.

Figure 4.

Omalizumab’s effects on illnesses. (A) Mean numbers of illnesses per subject were calculated for the groups treated with omalizumab versus standard therapy. Data shown are the risk ratio (95% confidence interval). (B) Mean numbers of viral illnesses per subject were calculated for the group treated with omalizumab versus standard therapy. Data shown are the risk ratio (95% confidence interval). (C) Symptom duration of respiratory illnesses is depicted for children in the omalizumab and standard therapy groups. The numbers represent the number of participants with at least one (A and C) illness or (B) viral illness from randomization to the end of the 90 days.